Active colorimetric bilayer polycaprolactone-eucalyptus oil@silk fibroin-bayberry anthocyanins (PCL-EO@SF-BAs) membrane with directional water transport (DWT) for food packaging.
Currently, designing smart membranes with multifunctional effectiveness is crucial to food freshness monitoring and retention. Herein, an active colorimetric Janus bilayer membrane with directional water transport (DWT) performance is constructed by electrospinning, which comprises a hydrophilic layer of silk fibroin-bayberry anthocyanins (SF-BAs) and a hydrophobic layer of polycaprolactone-eucalyptus oil (PCL-EO). The entities of BAs and EO are well dispersed in the fiber matrix by hydrogen bonds and physical interactions, respectively. BAs endow the membrane colorimetric response and antioxidant activity, and EO contributes to the antibacterial activity while DWT performance is generated from the asymmetric wettability of the two layers. The bilayer membrane has an accumulative one-way transport index of 1077%, an overall moisture management capacity of 0.76 and a water evaporation rate of 0.48 g h-1. Moreover, the release of BAs and EO was predominantly controlled by Fickian diffusion. As a pH-sensing indicator, PCL-EO@SF-BAs is highly sensitive to external pH stimuli and the response is reversible. In addition to freshness monitoring, PCL-EO@SF-BAs can extend the shelf-life of pork beyond 100% at 4 °C. Also, it can extend the shelf life of shrimp by approximately 70% at 25 °C with the synergistic effect of antibacterial activity and the DWT performance.


Detection of sleep onset by analysis of slow eye movements: a preliminary study of MSLT recordings.
Excessive daytime sleepiness (EDS) adversely impacts daily activity and quality of life. Evaluation of EDS should be as easy and effective as possible. Multiple sleep latency test (MSLT) represents the standard in EDS evaluation. It is, however, a long and expensive test. Slow eye movements (SEMs) occurring at the wake-sleep transition could be an easy and reliable marker of sleepiness. We have developed an automatic method for the detection of SEMs. In the present preliminary work we compare standard measurement of EDS with visual and automatic detection of SEMs, both performed on MSLT recordings. We compared sleep latency, obtained upon standard analysis of MSLT with visually and automatically detected SEM latency, in MSLT tests performed in a population of 20 subjects, (10 Obstructive Sleep Apnea Syndrome (OSAS) patients and 10 patients with normal MSLT). There were no significant differences between SEMs latency and standard determined sleep latency both in OSAS and normal MSLT patients. Automatic and visual analysis of SEMs gave comparable results. Both SEMs latency and sleep latency were significantly shorter in OSAS patients than normal MSLT patients. SEMs can be easily detected automatically and represent an effective marker of sleepiness in those conditions usually characterised by sleep onset with NREM sleep. Their performance equals that of standard measurements of sleep onset in MSLT recordings at least for OSAS and normal MSLT patients. Our study is, however, still preliminary and needs confirmation on a larger number of patients and in other clinical conditions characterised by EDS.


Characteristics of Sagittal Alignment in Patients with Severe and Rigid Scoliosis.
There has been increasing concern about the importance of sagittal alignment in the evaluation and treatment of spinal scoliosis. However, recent studies have only focused on patients with mild to moderate scoliosis. To date, little is known about the sagittal alignment in patients with severe and rigid scoliosis (SRS). This study was performed to evaluate the sagittal alignment in patients with SRS, and to analyze how it was altered after corrective surgery. In this retrospective cohort study, we included 58 patients with SRS who underwent surgery from January 2015 to April 2020. Preoperative and postoperative radiographs were reviewed, and the sagittal parameters mainly included thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacrum slope (SS), and sagittal vertical axis (SVA). The sagittal balance state was evaluated according to whether the PI minus the LL (PI-LL) was less than 9°, and the patients were divided into thoracic hyperkyphosis and normal groups based on whether the TK exceeded 40°. The Student's t test, Pearson's test, and Receiver operating characteristic (ROC) curve analysis were used to compare related parameters between the different groups. The mean follow-up duration was 2.8 years. Preoperatively, the mean PI was 43.6 ± 9.4°, and the mean LL was 65.2 ± 13.9°. Sixty-nine percent of patients showed sagittal imbalance, and they showed larger TK and LL values and smaller PI and SVA values than those with sagittal balance. Additionally, most patients (44/58) presented with thoracic hyperkyphosis; this group had smaller PI and SVA values than the normal patients. Patients with syringomyelia-associated scoliosis were more likely to present with thoracic hyperkyphosis. The TK and LL values were significantly decreased, and 45% of patients with preoperative sagittal imbalance recovered after surgery. These patients had a larger PI (46.4 ± 9.0° vs 38.3 ± 8.8°, P = 0.003) and a smaller TK (25.5 ± 5.2° vs 36.3 ± 8.0°, P = 0.000) at the final follow-up. Preoperative sagittal imbalance appears in the majority of SRS patients, accounting for approximately 69% of our cohort. Patients with small PI values or syringomyelia-associated scoliosis were more likely to present with thoracic hyperkyphosis. Sagittal imbalance can generally be corrected by surgery, except in patients with a PI less than 39°. To achieve good postoperative sagittal alignment, we recommend controlling the TK to within 31°.


Peanut agglutinin binding to human prolactin-producing pituitary adenomas.
Peanut agglutinin (PNA)-binding sites in human prolactin (PRL)-producing pituitary adenomas were examined by light and electron microscopy together with immunoblot analysis. At the light microscopic level, the majority of the PRL-producing adenoma cells stained positively for PNA in 15 of 20 cases. PNA binding observed in the cytoplasm had a granular appearance. PRL-producing cells adjacent to the adenoma tissue showed negative PNA staining. In normal pituitary glands, the PRL-positive glandular cells were negative for PNA staining. By electron microscopy, reaction products showing PNA-binding sites were detected in some of the secretory granules. Immunoblotting analysis revealed that the PRL bands corresponded to PNA-stained ones with the exception of the main 23-kDa band. PNA-binding sites have some relation to the secretory granules containing glycosylated forms of PRL. These observations suggest that PNA staining can be used as a valuable method to analyze human PRL-producing pituitary adenomas.


Venous Resection for Locally Advanced Pancreatic Cancer: Time Trend and Outcome Analysis of 65 Consecutive Resections at a High-Volume Center.
Locally advanced pancreatic cancer (LAPC) is a highly malignant carcinoma with an extremely poor prognosis. Vascular venous invasion is a frequent finding in patients with pancreatic cancer. The aim of this study was to investigate the morbidity, mortality, and survival of patients with advanced pancreatic cancer. We retrospectively reviewed our experience of 65 consecutive pancreatic surgeries with venous resection for pancreatic cancer in three hospitals: Ramon y Cajal (Madrid, Spain) from 2002 to 2004, Monteprincipe University Hospital (Madrid, Spain) from 2005 to 2006 and Sanchinarro University Hospital (Madrid, Spain) from 2007 to December 2017. Prognostic factors were analyzed by the log-rank test and a multivariate proportional hazard regression analysis. Major venous reconstruction was performed by primary lateral venorrhaphy in 11 patients (17%), primary end-to-end anastomosis in 46 (70.7%) and reconstruction with a Gore-Tex® patch (W.L. Gore & Associates, Inc., Flagstaff, AZ) in 8 (12.3%). In 58% of the patients, the pathological examination showed infiltration of the vascular specimen. About 85% of the procedures performed were R0. The perioperative morbidity rate with Dindo-Clavien classification = III was 21.5%. Tumor size and nodal status were the only prognostic variables, which significantly decreased survival by a multivariate analysis. Major vascular resection to achieve macroscopic tumor clearance can be performed safely with acceptable operative morbidity and mortality. Nevertheless, it is justified only in carefully selected cases.


Differences in major limb outcomes by indication for lower extremity endovascular revascularization in patients receiving hemodialysis.
The incidence of lower extremity artery disease (LEAD) in patient receiving hemodialysis is remarkably higher than the general population. The treatment strategy and prognosis for LEAD patients differs depending on whether a patient has intermittent claudication (IC) or critical limb-threatening ischemia (CLTI). However, the distinction between the prognosis in HD-dependent patients with IC and CLTI has not been fully elucidated. This study is to determine whether indication of PAD has a distinct impact on major adverse cardiovascular and cerebrovascular events (MACCE) and limb events in patients receiving hemodialysis. The current study included 2321 prospectively enrolled patients from the Tokyo taMA peripheral vascular intervention research ComraDE registry (UMIN-CTR no. UMIN000015100) between September 2014 and December 2016. Out of the enrolled patients, 1644 were not receiving hemodialysis (non-HD patients) and 603 were receiving hemodialysis (HD patients). A composite of all-cause death, myocardial infarction, and stroke events defined as MACCE; while limb events were defined as a composite of unscheduled major amputation, unscheduled major lower limb surgery, acute limb ischemia, unscheduled endovascular treatment, and target lesion revascularization. Propensity score matching was applied among the non-HD and HD patients, in whole group, IC subgroup, and CLTI subgroup. Kaplan-Meier analysis was used for the analysis of outcomes for the whole group, IC subgroup, and the CLTI subgroup. CLTI accounted for 75.5% of the HD patients, whereas IC was 63.4% in the non-HD patients. The HD patients exhibited more frequent below-the-knee lesions than those in the non-HD patients in both IC (p = 0.01) and CLTI (p < 0.001) subgroups. Overall, HD patients exhibited a significantly higher rate of MACCE at 24 months. This trend was similar for limb events in whole group and CLTI subgroup. In contrast, no significant differences in outcomes for limb events were found in IC subgroup. Although, prognosis after EVT in HD patients were significantly worse than non-HD patients, comparable outcome with non-HD patients was observed in the patients treated for IC. Clinical trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR No. UMIN000015100).


Comparison of cardiac autonomic modulation of athletes and non-athletes individuals with spinal cord injury at rest and during a non-immersive virtual reality task.
Cross-sectional study. To compare cardiac autonomic modulation of individuals with spinal cord injury (SCI) that practice different amounts of moderate to vigorous physical activity (PA) and able-bodied controls at rest and during a non-immersive Virtual Reality task. Athletes with SCI of wheelchair basketball, wheelchair tennis, wheelchair handball, WCMX (wheelchair motocross), and para-swimming were assessed at the Faca na Cadeira Institute, ICEL and Clube Espéria in São Paulo, Brazil; non-athletes with SCI and able-bodied controls were assessed at the Acreditando Centro de Recuperação Neuromotora, São Paulo, Brazil. One-hundred forty-five individuals were assessed: 36 athletes with traumatic SCI (41.1 ± 16.8 years old), 52 non-athletes with traumatic SCI (40.2 ± 14.1 years old), and 57 able-bodied individuals (39.4 ± 12.5 years old). Cardiac autonomic modulation was assessed through heart rate variability (HRV) measured in the sitting position at rest and during a VR game activity. We found significantly more favourable HRV for athletes with SCI when compared to non-athletes with SCI, but no differences between athletes with SCI and able-bodied controls. In addition, athletes and able-bodied controls showed adequate autonomic nervous system (ANS) adaptation (rest versus physical activity in VR), i.e., they experienced parasympathetic withdrawal during VR physical activity, which was not found in non-athletes with SCI. The practice of moderate to vigorous physical activity is associated with healthier cardiac autonomic modulation in adults with SCI, which may lead to more favourable health outcomes. ClinicalTrials.gov Identifier: NCT04618003, retrospectively registered.


Post-high-pressure temperature and time - Overlooked parameters in high pressure treatment of bacterial spores.
High pressure (HP) processing has high potential for bacterial spore inactivation with minimal thermal input. To advance HP germination and subsequent inactivation of spores, this study explored the physiological state of HP-treated spores using flow cytometry (FCM). Bacillus subtilis spores were treated at 550 MPa and 60 °C (very HP (vHP)) in buffer, incubated after the HP treatment, and stained for FCM analysis with SYTO16 indicating germination and propidium iodide (PI) indicating membrane damage. FCM subpopulations were analyzed depending on the HP dwell time (≤20 min), post-HP temperature (ice, 37 °C, 60 °C) and time (≤4 h), germination-relevant cortex-lytic enzymes (CLEs) and small-acid-soluble-proteins-(SASP)-degrading enzymes by using deletion strains. The effect of post-HP temperatures (ice, 37 °C) was additionally studied for moderate HP (150 MPa, 38 °C, 10 min). Post-HP incubation conditions strongly influenced the prevalence of five observed FCM subpopulations. Post-HP incubation on ice did not or only slowly shifted SYTO16-positive spores to higher SYTO16 levels. At 37 °C post-HP, this shift accelerated, and a shift to high PI intensities occurred depending on the HP dwell time. At 60 °C post-HP, the main shift was from SYTO16-positive to PI-positive subpopulations. The enzymes CwlJ and SleB, which are CLEs, seemed both necessary for PI or SYTO16 uptake, and to have different sensitivities to 550 MPa and 60 °C. Different extents of SASP degradation might explain the existence of two SYTO16-positive subpopulations. Shifts to higher SYTO16 intensities during post-HP incubation on ice or at 37 °C might rely on the activity and recovery of CLEs, SASP-degrading enzymes or their associated proteins from reversible HP-induced structural changes. These enzymes seemingly become active only during decompression or after vHP treatments (550 MPa, 60 °C). Based on our results, we provide a refined model of HP germination-inactivation of B. subtilis spores and an optimized FCM method for quantification of the safety-relevant subpopulation, i.e., vHP (550 MPa, 60 °C) superdormant spores. This study contributes to the development of mild spore inactivation processes by shedding light on overlooked parameters: post-HP incubation conditions. Post-HP conditions significantly influenced the physiological state of spores, likely due to varying enzymatic activity. This finding may explain inconsistencies in previous research and shows the importance of reporting post-HP conditions in future research. Furthermore, the addition of post-HP conditions as HP process parameter may open up new possibilities to optimize HP-based inactivation of spores for potential industrial applications in the food industry.


Cephalothin induced neutropenia during the treatment of bacterial endocarditis.
The occurrence of cephalothin induced neutropenia in 3 patients with infective endocarditis is described. In each patient, withdrawal of cephalothin was followed by rapid haematological recovery. It is apparent that granulocytopenia may frequently occur in patients receiving prolonged, high dose, intravenous cephalothin for the treatment of bacterial endocarditis.


Acute and subacute inhalation toxicity of dichlorosilane in male ICR mice.
Using male ICR mice, the LC50 and acute and subacute inhalation toxicity of dichlorosilane (SiH2Cl2, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron in diameter. The LC50 of DCS at 4-h exposure was 144 ppm (nominal concentration). In the acute inhalation study, ten mice in each group were exposed to 64 ppm (nominal concentration) DCS for 1, 2, 4 or 8 h. Body weight loss, wheezing and piloerection were observed in mice exposed for 2 h or more. Histopathologically, injury to the nasal mucosa and trachea were observed in all exposed mice. Mice exposed to 32 ppm (nominal concentration) DCS for 2 or 4 weeks also exhibited depression of body weight gain, wheezing and piloerection. Squamous metaplasia of the nasal mucosa and tracheal epithelium was observed in both 2- and 4-week exposure groups. Exposure to DCS was irritant or corrosive to the respiratory tract with both acute and subacute inhalation. Apart from silane (SiH4), toxic effects of DCS seem to be characterized by chloride compounds derived from DCS.


Analysis of acid-extractable tomato leaf proteins after infection with a viroid, two viruses and a fungus and partial purification of the "pathogenesis-related" protein p 14.
Gel electrophoretic analysis revealed marked alterations in the pattern of acid-extractable proteins from tomato leaves after infection with a viroid (PSTV), two viruses [tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV)], and a fungus (Cladosporium fulvum) when compared to the pattern from healthy leaves. A pathogen-specific appearance of new protein bands was only found after infection with TMV (MW 17,400 and 65,000), CMV (MW 9000 and 8000) and Cladosporium fulvum (MW 28,000). With the exception of the TMV coat protein (MW 17,400) it could not be established whether the other four proteins are coded for by the corresponding pathogen or by the host. Nine proteins with the apparent NW of 10,000, 11,000, 12,000, 13,000, 14,000, 25,000, 31,000, 33,000 and 38,000 showed an increase in their relative concentration which is most dramatic in the case of the protein with the MW of 14,000 called p14. A decrease was observed in four proteins with molecular weights of 14,500, 23,000, 30,000 and 105,000. Since all these alterations could be correlated with the severity of the disease symptoms but not with the nature of the pathogen they must be considered as a general pathophysiological response of the tomato plant to infection and symptom development. A partial purification of the most prominent "pathogenesis-related" protein p14 from tomato plants is described.


Ezogabine (retigabine).
Ezogabine (Potiga; Valeant Pharmaceuticals/GlaxoSmithKline), a potassium channel opener, was approved in June 2011 by the U.S. Food and Drug Administration (F.D.A.) for the adjunctive treatment of partial-onset seizures in adult patients. The same drug was granted marketing authorization for this indication in the European Union in March 2011, where it is known as retigabine (Trobalt).


Efficacy and safety of transbronchial lung biopsy for the diagnosis of lymphangioleiomyomatosis: A report of 24 consecutive patients.
Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease that occurs in women of childbearing age. LAM can be diagnosed on a clinical basis in patients with typical high-resolution computed tomography (HRCT) patterns and at least one other corroborating disease feature, such as chylothorax, angiomyolipoma, tuberous sclerosis complex or elevated serum vascular endothelial growth factor (VEGF)-D. However, patients who do not meet these criteria require tissue confirmation for a definitive diagnosis, and the utility of methods that are less invasive than surgical lung biopsy, such as transbronchial lung biopsy (TBLB), are not well studied. We retrospectively studied the efficacy and safety of TBLB for the diagnosis of LAM. From January 1991 to August 2015, 131 consecutive LAM patients were prospectively registered in our study, and a TBLB was conducted for 24 patients. We retrospectively studied the yield and safety of TBLB in this cohort. All 24 patients were women; the median age was 42 years. HRCT showed multiple round thin-walled cysts diffusely scattered throughout the lungs. The median level of serum VEGF-D was 2109 pg/mL. Characteristic pathological findings for LAM were identified in 17 patients (70.8%) by two expert pathologists. The %predicted value for diffusing capacity of carbon monoxide was significantly lower in the 17 TBLB-positive LAM patients compared to the seven TBLB-negative LAM patients (P = 0.046). There were no serious adverse events such as pneumothorax or uncontrollable bleeding due to TBLB. TBLB is a safe and effective method for the pathological diagnosis of LAM.


Single-Center Experience With Adjustable Annuloplasty Ring in Degenerative Mitral Regurgitation.
Owing to the complex anatomy of the mitral valve, successful surgical repair of degenerative regurgitation remains a challenging procedure in cardiac surgery. This paper aimed to report on our single-center experience with 20 patients who received an adjustable annuloplasty ring (Cardinal ring, ValtechCardio Ltd, Or Yehuda, Israel) as part of their mitral valve repair procedure. The device allows for intraoperative echocardiography-guided ring size adjustments under beating-heart conditions. All of the 20 patients left the operating room without any residual mitral regurgitation. There was no risk of systolic anterior movement (SAM) because of image-guided fine tuning of the ring before weaning the patient from bypass. Further multicenter data are required to prove the concept of adjustable annuloplasty devices.


Identifying Barriers to Delirium Screening and Prevention in the Pediatric ICU: Evaluation of PICU Staff Knowledge.
Delirium in the pediatric intensive care unit (PICU) setting is often unrecognized and undertreated. The importance of screening and identification of ICU delirium has been identified in both adult and pediatric literature. Delirium increases ICU morbidity, length of mechanical ventilation and length of stay. The objective of this study was to determine the current knowledge level about delirium and its risk factors among pediatric critical care nurses through a short questionnaire. We hypothesized that before a targeted educational intervention, PICU care providers do not have an adequate knowledge base for accurate screening and diagnosis of delirium in critically ill children. A 17 question online survey was given to all nurses in a tertiary 36-bed PICU to assess current knowledge about delirium in children. The response rate was 73% (105/143). When asked to identify the correct way to diagnose pediatric delirium, 11.4% of nurses surveyed (12/105) incorrectly believed that Glasgow Coma Score is the appropriate screening tool. A large proportion of respondents (40/105) believed that benzodiazepines are helpful in treatment of delirium. The results of the survey identified specific knowledge gaps about risk factors and treatment of pediatric delirium in the critically ill child. There is a critical need for education about pediatric delirium and its risk factors among PICU staff prior to unit-wide implementation of a delirium screening and prevention program, specifically with regards to screening methods and pharmacologic risk factors. These results are likely generalizable to all physicians, nurses and staff who care for critically ill children.


Changes in the activities of protein kinase modulators in the cerebellum of mice due to ethanol, caffeine, or phenobarbital administration.
Decreased activities of both the inhibitory modulator of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase (A-PK) as well as the stimulatory modulator of guanosine 3':5'-monophosphate (cGMP)-dependent protein kinase (G-PK) from the mouse cerebellum were noted due to the administration of excessive doses of ethanol, caffeine, and phenobarbital for up to 28 days. The dose-dependent of the inhibition of A-PK or the stimulation of G-PK was observed as a function of the amount of protein kinase modulators in the cerebellum of mice receiving different doses of ethanol.


Variations of left atrial activation patterns in congestive heart failure.
We report about a case of a patient admitted to the Intensive Cardiac Care Unit for severe congestive heart failure which showed modification of P-wave morphology and duration, correlated with the clinical evolution. In the case here described, we show that ECG analysis, specifically P wave, allow us to assess the hemodynamic evolution of the acute decompensated heart failure patient. Electrocardiographic examination is the first and the most simple and available diagnostic tool in the evaluation of patients with cardiac diseases. Usually, P-wave evaluation is not carefully assessed, in spite of very useful informations we can draw from its interpretation. We report about a patient admitted to our Intensive Cardiac Care Unit (ICCU) for severe congestive heart failure which showed peculiar modification of P-wave morphology and duration, well correlated with the clinical course.


TERRA and RAD51AP1 at the R&D-loop department of ALT telomeres.
In this issue of Molecular Cell, Kaminski et al. and Yadav et al. demonstrate that RAD51AP1 and TERRA non-coding RNA positively regulate the alternative mechanism of telomere maintenance by promoting D-loop formation and chromatin-directed mechanisms to suppress transcription-collision events during ALT telomere synthesis.


Autism as a difference or a disorder? Exploring the views of individuals who use peer-led online support groups for autistic partners.
Individuals who use peer-led online support groups for partners of autistics describe diverse views of autism, with some describing autism as a difference and others describing it as a disorder. I conducted online interviews with 162 non-autistics who believed they were in relationships with autistics and who participated in online support groups on social media. I analyzed their responses by constantly comparing each interview to previous interviews to develop a theory about their social experiences. As many as one-third of autistics participate in romantic relationships, and many of their partners seek support through groups on social media. Few studies explore what it is like to be a non-autistic person who is in a relationship with an autistic person. The way that participants viewed autism influenced the way that they viewed themselves, their partners, and their relationships. Many participants who were dissatisfied in their relationships shared that they believed their partners were autistic, but their partners had never been formally evaluated and did not self-identify as autistic. Future research should explore ways that autism labels are (mis)applied by the general public based on negative stereotypes about autism.


Subclinical cardiac dysfunction may impact on fluid and vasopressor administration during early resuscitation of septic shock.
According to the Surviving Sepsis Campaign (SSC) fluids and vasopressors are the mainstays of early resuscitation of septic shock while inotropes are indicated in case of tissue hypoperfusion refractory to fluids and vasopressors, suggesting severe cardiac dysfunction. However, septic cardiac disfunction encompasses a large spectrum of severities and may remain "subclinical" during early resuscitation. We hypothesized that "subclinical" cardiac dysfunction may nevertheless influence fluid and vasopressor administration during early resuscitation. We retrospectively reviewed prospectically collected data on fluids and vasoconstrictors administered outside the ICU in patients with septic shock resuscitated according to the SSC guidelines that had reached hemodynamic stability without the use of inotropes. All the patients were submitted to transpulmonary thermodilution (TPTD) hemodynamic monitoring at ICU entry. Subclinical cardiac dysfunction was defined as a TPTD-derived cardiac function index (CFI) ≤ 4.5 min-1. At ICU admission, subclinical cardiac dysfunction was present in 17/40 patients (42%; CFI 3.6 ± 0.7 min-1 vs 6.6 ± 1.9 min-1; p < 0.01). Compared with patients with normal CFI, these patients had been resuscitate with more fluids (crystalloids 57 ± 10 vs 47 ± 9 ml/kg PBW; p < 0.01) and vasopressors (norepinephrine 0.65 ± 0.25 vs 0.43 ± 0.29 mcg/kg/min; p < 0.05). At ICU admission these patients had lower cardiac index (2.2 ± 0.6 vs 3.6 ± 0.9 L/min/m2, p < 0.01) and higher systemic vascular resistances (2721 ± 860 vs 1532 ± 480 dyn*s*cm-5/m2, p < 0.01). In patients with septic shock resuscitated according to the SSC, we found that subclinical cardiac dysfunction may influence the approach to fluids and vasopressor administration during early resuscitation. Our data support the implementation of early, bedside assessment of cardiac function during early resuscitation of septic shock.


Thermoelectric signature of quantum critical phase in a doped spin-liquid candidate.
Quantum spin liquid is a nontrivial magnetic state of longstanding interest, in which spins are strongly correlated and entangled but do not order; further intriguing is its doped version, which possibly hosts strange metal and unconventional superconductivity. A promising candidate of the doped spin liquid is a triangular-lattice organic conductor, κ-(BEDT-TTF)4Hg2.89Br8, recently found to hold metallicity, spin-liquid-like magnetism, and BEC-like superconductivity. The nature of the metallic state with the spin-liquid behaviour is awaiting to be further clarified. Here, we report the thermoelectric signature that mobile holes in the spin liquid background are in a quantum critical state and it pertains to the BEC-like superconductivity. The Seebeck coefficient divided by temperature, S/T, is enhanced on cooling with logarithmic divergence indicative of quantum criticality. Furthermore, the logarithmic enhancement is correlated with the superconducting transition temperature under pressure variation, and the temperature and magnetic field profile of S/T upon the superconducting transition change with pressure in a consistent way with the previously suggested BEC-BCS crossover. The present results reveal that the quantum criticality in a doped spin liquid emerges in a phase, not at a point, and is involved in the unconventional BEC-like nature.


Efficacy of antimicrobial activity of slow release silver nanoparticles dressing in post-cardiac surgery mediastinitis.
We report our preliminary experience in post-cardiac surgery mediastinitis using a recently introduced silver-releasing dressing claiming prompt antibacterial activity. Acticoat, a silver nanoparticles slow release dressing was used in four patients with documented post-cardiac surgery mediastinitis and persistently positive microbiological cultures despite vacuum-assisted closure (VAC) therapy. In all four patients negative cultures were obtained within a maximum of 72 h and patients were discharged within a maximum of 20 days.


CPP-ZFN: a potential DNA-targeting anti-malarial drug.
Multidrug-resistant Plasmodium is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death. Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells. Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the Plasmodium genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between Plasmodium and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to Plasmodium-infected RBCs (iRBCs) and different Plasmodium organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more Plasmodium cell membrane translocation peptide seems achievable. Targeting of the Plasmodium genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.


Directed Differentiation of Embryonic Stem Cells Into Cardiomyocytes by Bacterial Injection of Defined Transcription Factors.
Forced expression of defined transcriptional factors has been well documented as an effective method for cellular reprogramming or directed differentiation. However, transgene expression is not amenable for therapeutic application due to potential insertional mutagenesis. Here, we have developed a bacterial type III secretion system (T3SS)-based protein delivery tool and shown its application in directing pluripotent stem cell differentiation by a controlled delivery of transcription factors relevant to early heart development. By fusing to an N-terminal secretion sequence for T3SS-dependent injection, three transcriptional factors, namely Gata4, Mef2c, and Tbx5 (abbreviated as GMT), were translocated into murine embryonic stem cells (ESCs), where the proteins are effectively targeted to the nucleus with an average intracellular half-life of 5.5 hours. Exogenous GMT protein injection activated the cardiac program, and multiple rounds of GMT protein delivery significantly improved the efficiency of ESC differentiation into cardiomyocytes. Combination of T3SS-mediated GMT delivery and Activin A treatment showed an additive effect, resulting in on average 60% of the ESCs differentiated into cardiomyocytes. ESC derived cardiomyocytes displayed spontaneous rhythmic contractile movement as well as normal hormonal responses. This work serves as a foundation for the bacterial delivery of multiple transcription factors to direct cell fate without jeopardizing genomic integrity.


Relationship of serum lipid profiles in preeclampsia and normal pregnancy, Bangladesh.
The purpose of this present study to investigate the lipid profile levels and basal body mass index in preeclampsia and normal pregnancy in Bangladeshi women. This case-control study was conducted at Sheba Hospital Kaligonj Bangladesh with 70 participants among 35 normal pregnancy (control) and 35 preeclampsia women (case) were enrolled from August 2018 to July 2019. Blood samples were obtained for analysis of total cholesterol, triglyceride and high-density lipoprotein by enzymatic assays and low-density lipoprotein by using Fried Ewald's formula in between 22-36 weeks of gestation. This study found the mean age of preeclampsia and normal pregnancy women were 24.71±2.56 and 23.09±2.1 respectively with significant (P= 0.005). Basal body mass index, total cholesterol, triglyceride and low-density lipoprotein significantly higher (P=0.002), (P= 0.000), (P= 0.022) and (P=0.000) in preeclampsia compared to normal pregnancy respectively. While high-density lipoprotein comparatively lower in preeclampsia than normal pregnancy and consider significant as (P=0.037). Abnormal lipid profile and increased body mass index is contributed to the development of preeclampsia. The frequent antenatal monitoring of lipid profiles provides the status which helps to require management and reduces the preeclampsia which enhances maternal and fetal wellbeing and fetal outcome.


Outcome and risk factors in surgery of descending thoracic aneurysms.
In a series of 100 consecutive patients operated upon for aneurysmatic lesions of the descending thoracic aorta, the mean age was 52 +/- 16 years (male = 81, female = 19). There were 31 dissections (acute 10, chronic 21); 28 post-traumatic aneurysms (ruptured 5, acute 7, chronic 16); 22 arteriosclerotic aneurysms (ruptured 1, chronic 21); 11 thoracoabdominal aneurysms, 5 anastomotic aneurysms and 3 mycotic aneurysms. No symptomatic patient was refused. Preoperative risk factors were graded on a scale of 6 by counting 1 point for each of the following elements: central nervous system disease; heart, pulmonary, and renal disease; arterial hypertension, age greater than 60. In-hospital mortality and paraplegia for the whole series were 25% and 7% respectively. In acute dissection, the mortality was 6/10 patients versus 2/21 in chronic events. In post-traumatic aneurysms, mortality was 2/5 in ruptured, 2/7 in acute and 0/16 in chronic events. In arteriosclerotic aneurysms, mortality was 1/2 in ruptured and 6/20 in chronic events. In thoracoabdominal aneurysms, mortality was 5/11, in anastomotic 1/5 and in mycotic 0/3 patients. The mean number of risk factors in non-survivors versus survivors was significantly higher in acute dissection, chronic dissection, chronic arteriosclerotic aneurysms and thoracoabdominal aneurysms. Rupture and acute events are related to a high surgical mortality. Non-survivors appear to have significantly more preoperative risk factors.


Very well-differentiated gastric carcinoma of intestinal type: analysis of diagnostic criteria.
Very well-differentiated gastric adenocarcinoma of intestinal type is a rare variant of gastric cancer characterized by low-grade nuclear atypia, and for which the diagnostic criteria and clinical behavior are not fully established. This study presents a detailed histologic, immunohistochemical, and clinical analysis of 21 cases. Nuclear atypia was mild in all cases. Characteristic architectural features of this gastric adenocarcinoma variant were pit and glandular anastomosis, spiky glands, distended glands, discohesive cells, abortive glands, and glandular outgrowth. At least three of these features were present in all the cases. Retrospective review of preoperative biopsies in 18 patients revealed that half of the biopsies were originally reported as negative or indeterminate for malignancy. On the basis of immunohistochemical stains for intestinal (MUC2, CD10, and CDX-2) and gastric (MUC5AC and MUC6) markers, 11 (52%) cases had an intestinal immunophenotype and 10 (48%) cases had a mixed immunophenotype. Foci of discohesive neoplastic cells, indicating dedifferentiation toward a poorly cohesive carcinoma, were observed exclusively in neoplasms of mixed immunophenotype (n=5). All patients with follow-up but one were alive without disease at a mean of 19 months (range 1-60 months). One individual with a pT4 tumor with associated poorly cohesive carcinoma died of disease. In summary, very well-differentiated gastric adenocarcinomas are diagnostically challenging. Architectural features are critical to making the diagnosis. Cases with pure intestinal immunophenotype have not been associated with transformation into poorly cohesive carcinoma, and appear to behave as biologically low grade. Those with mixed immunophenotype appear more likely to dedifferentiate and behave more aggressively.


Profiling human pathogenic repeat expansion regions by synergistic and multi-level impacts on molecular connections.
Whilst DNA repeat expansions cause numerous heritable human disorders, their origins and underlying pathological mechanisms are often unclear. We collated a dataset comprising 224 human repeat expansions encompassing 203 different genes, and performed a systematic analysis with respect to key topological features at the DNA, RNA and protein levels. Comparison with controls without known pathogenicity and genomic regions lacking repeats, allowed the construction of the first tool to discriminate repeat regions harboring pathogenic repeat expansions (DPREx). At the DNA level, pathogenic repeat expansions exhibited stronger signals for DNA regulatory factors (e.g. H3K4me3, transcription factor-binding sites) in exons, promoters, 5'UTRs and 5'genes but were not significantly different from controls in introns, 3'UTRs and 3'genes. Additionally, pathogenic repeat expansions were also found to be enriched in non-B DNA structures. At the RNA level, pathogenic repeat expansions were characterized by lower free energy for forming RNA secondary structure and were closer to splice sites in introns, exons, promoters and 5'genes than controls. At the protein level, pathogenic repeat expansions exhibited a preference to form coil rather than other types of secondary structure, and tended to encode surface-located protein domains. Guided by these features, DPREx ( http://biomed.nscc-gz.cn/zhaolab/geneprediction/# ) achieved an Area Under the Curve (AUC) value of 0.88 in a test on an independent dataset. Pathogenic repeat expansions are thus located such that they exert a synergistic influence on the gene expression pathway involving inter-molecular connections at the DNA, RNA and protein levels.


Ultrafast Non-Equilibrium Synthesis of Cathode Materials for Li-Ion Batteries.
The synthesis of cathode materials plays an important role in determining the production efficiency, cost, and performance of lithium-ion batteries. However, conventional synthesis methods always experience a slow heating rate and involve a complicated multistep reaction process and sluggish reaction dynamics, leading to high energy and long time consumption. Herein, a high-temperature shock (HTS) strategy is reported for the ultrafast synthesis of cathode materials in seconds. The HTS process experiences an ultrahigh heating rate, leading to a non-equilibrium reaction and fast reaction kinetics, and avoids high energy and long time consumption. Mainstream cathode materials (such as LiMn2 O4 , LiCoO2 , LiFePO4 , and Li-rich layered oxide/NiO heterostructured material) are successfully synthesized with pure phases, oxygen vacancies, ultrasmall particle sizes, and good electrochemical performance. The HTS process not only provides an efficient synthesis approach for cathode materials, but also can be extended beyond lithium-ion batteries.


Effects of low-repetition jump exercise on osteogenic response in rats.
Jump exercise in rats creates high-impact loading on lower limbs and results in the promotion of osteogenesis. Although we clarified that a few loadings per day could increase bone mass and strength within 8 weeks, we did not observe an osteogenic response at the onset of the training period. The purpose of this study was to clarify whether the bone formation rate measured by the double-label immunofluorescence method increases with a few loadings for a short period. Forty female Wistar rats, 10 weeks old, were divided into a control group and three exercise groups: the 10 jumps/day (10 J) group, 40 jumps/day (40 J) group, and 100 jumps/day (100 J) group. The exercise groups were trained on days 1, 3, and 5, the fluorescent labels were injected on days 5 and 12, and the experiment ended on day 16. The bone formation rates were greater in all exercise groups compared with the control group and were significantly greater in the 40 J and 100 J groups than in the 10 J group. These data show that only 10 repetitions/day loading promotes the osteogenic response within a short period from the onset of the training.


A novel risk stratification system "Angiographic GRACE Score" for predicting in-hospital mortality of patients with acute myocardial infarction: Data from the K-ACTIVE Registry.
The Global Registry of Acute Coronary Events (GRACE) score is the most accurate risk assessment system for acute myocardial infarction (AMI), which was proposed in Western countries. However, it is unclear whether GRACE score is applicable to the present Japanese patients with a high prevalence of emergent percutaneous coronary intervention (PCI) and vasospasm. This study aimed to clarify the usefulness of GRACE risk score for risk stratification of Japanese AMI patients treated with early PCI and to evaluate a novel risk stratification system, "angiographic GRACE score," which is the GRACE risk score adjusted by the information of the culprit coronary artery and its flow at pre- and post-PCI, to improve its predicting availability. The subjects were 1817 AMI patients who underwent PCI within 24 h of onset between October 2015 and August 2017 and were registered in Kanagawa Acute Cardiovascular (K-ACTIVE) Registry via survey form. The association between the clinical parameters and in-hospital mortality was investigated. A total of 79 (4.3%) in-hospital deaths were identified. The C-statistics for the in-hospital mortality of the GRACE score was 0.86, which was higher than that of the other conventional risk factors, including age (0.65), systolic blood pressure (0.70), heart rate (0.62), Killip classification (0.77), and serum levels of creatinine (0.68) and peak creatine kinase (0.74). The angiographic GRACE score improved the C-statistics from 0.86 of the original GRACE score to 0.89 (p < 0.05). In the setting of the cut-off value at 200, in-hospital mortality in the patients with the angiographic GRACE score <200 was 0.6%, which was relatively lower than those with ≥200, 9.4%. The GRACE score is a useful predictor of in-hospital mortality among Japanese AMI patients in the PCI era. Moreover, the angiographic GRACE score could improve the predicting availability.


Longitudinal study of lung mechanics in normal infants.
Lung mechanics and partial forced expiratory flows were measured serially in seven normal infants during the first year of life. Lung mechanics were measured by the end inspiratory occlusion technique and partial forced expiratory flows by the rapid chest compression method. Thoracic gas volume, compliance, and partial forced expiratory flows measured at functional residual capacity progressively increased with age and correlated with height cubed. Respiratory system resistance progressively fell whereas volume-corrected flows remained fairly constant over the study period. These findings provide longitudinal lung function data and support the concept of isotropic lung growth.


COVID-19 can lead to rapid progression of cervical intraepithelial neoplasia by dysregulating the immune system: A hypothesis.
COVID-19 is a multisystem disease and cause of a global pandemic. Lately, cases of disease progression of HPV-infected CIN under SARS-CoV-2 infection were reported giving rise to the hypothesis of direct virus-infection induced pro-carcinogenic effect of SARS-CoV-2. We herein present a case of rapid progression from HPV-induced CIN 2 to microinvasive carcinoma within three months under COVID-19 without direct virus infection. Histopathologic evaluation, Fluorescence-in-situ hybridization and qRT-PCR against SARS-CoV-2 RNA as well as gene expression analysis were performed from the available FFPE-tissue and accompanied by an analysis of white blood cell differential. No signs of direct SARS-CoV-2 infection or COVID-19 typical alterations of cervical tissue were found. As expected, p53 decreased in expression with progression of dysplasia, while APOBEC3A and VISTA showed a decrease in expression contrary to observations in dysplasia progression. PD-L1 was expressed consistently or increased slightly but did not show the expected strong induction of expression. DNMT1 showed an increase in expression in CIN III and a slight decrease in carcinoma, while DNMT3a is consistently expressed in CIN II and decreased in carcinoma. Blood tests after COVID-19 showed substantial reduction of lymphocytes, eosinophils, T-cells, and NK-cells. Our results hint at an indirect effect of COVID-19 on the cervical neoplasm. We conclude that the immune system might be preoccupied and exhausted by the concurring COVID-19 disease, leading to less immunological pressure on the HPV-infected cervical dysplasia enabling rapid disease progression. Further, indirect proangiogenic and proinflammatory micromilieu due to the multisystemic effects of COVID-19 might play an additional role.


Differentiation of renal Na(+)-K(+)-ATPase in control and streptozotocin-induced diabetic mice by G-protein acting toxins and phorbol esters.
The specific activity of Na(+)-K(+)-ATPase in the renal medulla and cortex of 50-day-old streptozotocin (STZ)-induced diabetic mice was increased 58% and 50%, respectively, as compared to controls. Km values of Na+ and K+ for this enzyme were unaltered, while that of ATP was decreased in diabetic mice. The Na(+)-K(+)-ATPase in control medulla and cortex was activated by both cholera and pertussis toxins, while this effect was abolished in diabetics. Since dibutyryl cAMP stimulates cortical Na(+)-K(+)-ATPase activity in control mice, the activation effect of cholera toxin on this enzyme might be due to its interaction with a Gs-protein and the persistent stimulation of adenylate cyclase activity, while the effect of pertussis toxin might be due to its masking of the inhibitory action of a Gi-protein on adenylate cyclase activity. However, the protein kinase C (PKC)-associated Na(+)-K(+)-ATPase might also be quiescent in diabetes, because the stimulating effect of phorbol 12,13-dibutyrate (PDBu) and phorbol 12-myristate 13-acetate (PMA) on this enzyme was abolished in diabetic cortex. In addition, nicardipine and ouabain were found to have differential effects on this enzyme derived from control and diabetic mice.


An injectable photo-cross-linking silk hydrogel system augments diabetic wound healing in orthopaedic surgery through spatiotemporal immunomodulation.
The complicated hyperglycaemic and chronic inflammation of diabetic wounds in orthopaedic surgery leads to dysregulated immune cell function and potential infection risk. Immune interventions in diabetic wounds face a possible contradiction between simultaneous establishment of the pro-inflammatory microenvironment in response to potential bacterial invasion and the anti-inflammatory microenvironment required for tissue repair. To study this contradiction and accelerate diabetic-wound healing, we developed a photocurable methacryloxylated silk fibroin hydrogel (Sil-MA) system, co-encapsulated with metformin-loaded mesoporous silica microspheres (MET@MSNs) and silver nanoparticles (Ag NPs). The hydrogel system (M@M-Ag-Sil-MA) enhanced diabetic-wound healing via spatiotemporal immunomodulation. Sil-MA imparts a hydrogel system with rapid in situ Ultra-Violet-photocurable capability and allows preliminary controlled release of Ag NPs, which can inhibit bacterial aggregation and create a stable, sterile microenvironment. The results confirmed the involvement of Met in the immunomodulatory effects following spatiotemporal dual-controlled release via the mesoporous silica and Sil-MA. Hysteresis-released from Met shifts the M1 phenotype of macrophages in regions of diabetic trauma to an anti-inflammatory M2 phenotype. Simultaneously, the M@M-Ag-Sil-MA system inhibited the formation of neutrophil extracellular traps (NETs) and decreased the release of neutrophil elastase, myeloperoxidase, and NETs-induced pro-inflammatory factors. As a result of modulating the immune microenvironmental, the M@M-Ag-Sil-MA system promoted fibroblast migration and endothelial cell angiogenesis in vivo, with verification of enhanced diabetic-wound healing accompanied with the spatiotemporal immunoregulation of macrophages and NETs in a diabetic mouse model. Our findings demonstrated that the M@M-Ag-Sil-MA hydrogel system resolved the immune contradiction in diabetic wounds through spatiotemporal immunomodulation of macrophages and NETs, suggesting its potential as a promising engineered nano-dressing for the treatment of diabetic wounds in orthopaedic surgery.


Evaluation of lead, cadmium, chromium, copper and zinc by atomic absorption spectroscopy in durum wheat milling products in relation to the percentage of extraction.
36 samples representative of the 1981 Italian durum wheat crop were separated by an industrial Italian milling process and the products obtained analyzed by AAS for their Pb, Cd, Cr, Cu, Zn content. The results obtained were: Pb ranging from 0.04 to 0.80 ppm, Cd from 0.02 to 1.39 ppm, Cr from 0.05 to 1.60 ppm, Cu from 1.8 to 39.7 ppm and Zn from 8.8 to 117.6 ppm. Although Cr content was relatively homogeneous, Pb, Cd, Cu and Zn distribution in the various mill products proved to be rather inhomogeneous. Maximum contamination for Pb, Cd and Cr, was appreciably lower than in previous studies.


Dipeptidyl peptidase-4 as a new target of action for type 2 diabetes mellitus: a systematic review.
Type 2 diabetes mellitus is a metabolic disease leading to microvascular and macrovascular complications including coronary artery disease and stroke. Management of diabetes has been challenging, particularly in the presence of the enormous prevalence of obesity. In recent years, various inhibitors of the enzyme dipeptidyl peptidase (DPP)-4 have been developed to treat diabetes. The enzyme DPP-4 cleaves incretins, which, among other functions, stimulate insulin and suppresses glucagon. Inhibition of this enzyme results in an increase in the half-life and the sustained physiologic action of incretins, leading to an improvement in hyperglycemia. One such agent, namely sitagliptin (MK-04,310), has been introduced into the United States market, and another agent, vildagliptin (LAF237), is being used in Europe and elsewhere. This article is intended to evaluate the effectiveness of DPP-4 inhibitors as a therapeutic modality for managing type 2 diabetes. The authors conducted a literature search of various databases to identify the clinical trials involving the DPP inhibitors and concluded that the DPP-4 inhibitors, for example, sitagliptin and vildagliptin, are efficacious for managing diabetes as monotherapy or combination therapy.


Substantially elevated TSH, not traditional clinical subclinical thyroid disorder groupings, are associated with smaller LDL-P mean size: ELSA-Brasil.
LDL appears to drive atherogenesis in overt hypothyroidism, but in subclinical dysfunction, its role is not completely elucidated. The aim of this study was to evaluate subfractions of LDL in subclinical (SC) thyroid disorders. Individuals were divided into three groups by baseline thyroid function (SC hypothyroidism, euthyroidism, and SC hyperthyroidism). LDL particle (LDL-P) subfractions were analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy. The association between LDL-P subfractions and thyroid groups and quintiles was evaluated by linear regression models. We evaluated 3304 participants (54.1% women, 51.2% white, mean age 50.6 ± 8.7 years). In the univariate analysis, small LDL particle concentrations (SLDL-P) were not different between SC hypo- and hyperthyroidism compared to euthyroid individuals (p = 0.485 and p = 0.314, respectively). Large LDL-P (LDL-P) levels also did not differ in SC hyperthyroidism and SC hypothyroidism compared to euthyroidism (p = 0.698 and 0.788 respectively). Intermediate LDL-P levels were not different across the groups. These numbers did not materially change in multivariate analysis. However, we also analyzed LDL subfractions according to quintiles of TSH. We showed that in the higher TSH quintile LDL subfractions presented a significantly smaller mean size of LDL subfractions compared to the first quintile. SC thyroid disorders are not associated with significant changes in LDL-P subfractions measured by NMR spectroscopy. However, it seems that the LDL mean size decreases as TSH levels increase, which may represent a more atherogenic lipid profile.


A visual chiroptical system with chiral assembly graphene quantum dots for D-phenylalanine detection.
Chirality is a fundamental phenomenon of nature, and the enantioselective recognition of amino acids isomers is especially important for life science. In this study, chiroptical system based on chiral assembly graphene quantum dots (GQDs) was developed for visual testing of D-phenylalanine (D-Phe). Here, GQDs were used as the fluorescent element, and chiral functional moieties of 1,3,5-triformylphloroglucinol-functionalized chiral ( +)-diacetyl-L-tartaric anhydride (TPTA) were used as the chiral recognition elements. Based on the formed chiral microenvironment, the fluorescence intensity of TPTA-assembled GQDs had a good linear relationship with D-Phe in the concentration range of 0.1-5 μM, and the detection limit was 0.023 μM. According to the variation in luminance of TPTA-assembled GQDs, visual testing to D-Phe was realized using a smartphone-assisted chiroptical system with a detection limit of 0.050 μM. The spiked recoveries of both chiroptical sensing methods based on TPTA-assembled GQDs from the food matrix ranged from 86.20 to 110.0%. Furthermore, TPTA-assembled GQDs were successfully applied to intracellular chiroptical imaging in response to D-Phe in vitro. The developed chiral nanomaterial TPTA-assembled GQDs with excellent photochemical stability, optical properties, and bioimaging capabilities provide a promising technique for the visual detection of amino acid isomers in the field of smart devices.


A quantitative model for simultaneous brightness induction.
The brightness that results from stimulating a particular test-region of the retina may be depressed or enhanced by simultaneous stimulation of other "inducing"-regions. The test-region brightness may be affected by contiguous inducing-regions (local contrast effects), and by non-contiguous inducing regions (long-range effects sometimes called "assimilation"). We describe a computational model for early vision that can predict the results of brightness-matching procedures commonly used to measure these phenomena. According to this model, brightness depression reflects primarily lateral inhibition that underlies local contrast effects; whereas brightness enhancement results from processes similar, in spirit, to those described in Helson's adaptation-level theory.


Carbohydrate intake is the main determinant of growth in infants born <33 weeks' gestation when protein intake is adequate.
We investigated the relative contribution of macronutrients to postnatal growth in preterm infants born <33 wk of gestation. An audit of daily parenteral and enteral intakes of protein, carbohydrate, fat, energy, and growth (daily weight, weekly length, and head circumference) from birth to discharge home in 138 infants at <33 wk of gestation admitted to an Australian tertiary hospital was done. A mixed-model analysis of variance with random effects (slope and intercept) for subject and controlling for time, sex, gestational age, and total energy was used to determine the relative contribution of macronutrients to growth. A higher energy intake (kilocalories per day) had a positive influence on growth. With total energy held constant, the contribution of carbohydrate to total energy had a positive relation to weight, length, and head circumference gains; protein had no relation and fat was negatively associated. For every 1% increase in energy from carbohydrate, there was a 2.3-g/d increase in weight (95% confidence interval 1.6-3.0, P < 0.0001), a 0.013-cm/d increase in length (95% confidence interval 0.003-0.022, P = 0.007), and a 0.015-cm/d increase in head circumference (95% confidence interval 0.009-0.022, P < 0.0001). A re-examination of the macronutrient balance in the diet of preterm infants is required in relation to optimizing growth.


Salubrinal, ER stress inhibitor, attenuates kainic acid-induced hippocampal cell death.
Kainic acid (KA)-induced neuronal death is closely linked to endoplasmic reticulum (ER) and mitochondrial dysfunction. Parkin is an ubiquitin E3 ligase that mediates the ubiquitination of the Bcl-2 family of proteins and its mutations are associated with neuronal apoptosis in neurodegenerative diseases. We investigated the effect of salubrinal, an ER stress inhibitor, on the regulation of ER stress and mitochondrial apoptosis induced by KA, in particular, by controlling parkin expression. We showed that salubrinal significantly reduced seizure activity and increased survival rates of mice with KA-induced seizures. We found that salubrinal protected neurons against apoptotic death by reducing expression of mitochondrial apoptotic factors and elF2α-ATF4-CHOP signaling proteins. Interestingly, we showed that salubrinal decreased the KA-induced parkin expression and inhibited parkin translocation to mitochondria, which suggests that parkin may regulate a cross-talk between ER and mitochondria. Collectively, inhibition of ER stress attenuates mitochondrial apoptotic and ER stress pathways and controls parkin-mediated neuronal death following KA-induced seizures.


Long-term outcome after totally thoracoscopic ablation for atrial fibrillation.
Totally thoracoscopic ablation for symptomatic atrial fibrillation (AF) refractory to drug or catheter based therapy is indicated as a Class 2A recommendation according to latest guidelines. Evidence for long-term rhythm control and stroke reduction is limited. The aim of this study was to report on long-term outcome after totally thoracoscopic ablation. In total 82 consecutive patients were included that underwent totally thoracoscopic ablation including left appendage closure (2012-2013). The primary outcome was freedom from atrial arrhythmia recurrence. Secondary outcomes were survival, freedom from cerebrovascular events, freedom from reablation and definite pacemaker implantation. The mean age was 59.9 ± 8.6 years and 71% were male. The mean CHA2 DS2 -VASc score was 1.2 ± 1.0. The overall freedom from atrial arrhythmia was 60% after a mean follow up of 4.0 ± 0.6 years. Freedom from cerebrovascular events was 98.8% after mean follow-up of 4.4 ± 0.3 years and overall survival was 98.8%, with one noncardiac related death. The observed rate of ischemic stroke, hemorrhagic stroke or transient ischemic attack was 0.3 per 100 patient-years. Totally thoracoscopic ablation is an effective sustainable rhythm control therapy for AF with a reasonable recurrence rate and low stroke rate when performed in dedicated AF centers.


The effect of home-based resistance exercise training in people with type 2 diabetes: A randomized controlled trial.
To evaluate the effects of pragmatic home-based resistance exercise training on glycated haemoglobin (HbA1c) as well as muscle strength and body composition in people with type 2 diabetes. People with type 2 diabetes were randomized (1:1) to usual care or usual care plus home-based resistance exercise for 32 weeks. The changes in HbA1c, body composition, physical function, quality of life, continuous glucose monitoring and liver fat were compared by randomized group using linear regression. This study recruited 120 participants (female: n = 46 [38%], age 60.2 (9.4) years, BMI 31.1 (5.4) kg.m-2 ), 64 to intervention and 56 to usual care. Intention to treat analysis revealed no effect on HbA1c (difference in difference: -0.4 mmol/mol, 95% confidence interval [CI]: -3.26, 2.47; p = 0.78) but the intervention increased the number of push-ups (3.6 push-ups, 95% CI: 0.8, 6.4), arm lean mass (116 g, 95% CI: 6, 227) and leg lean mass (438 g, 95% CI 65, 810) and decreased liver fat (-1.27%, 95% CI -2.17, -0.38), with no differences in other outcomes. Per-protocol analysis revealed similar results. Home-based resistance exercise is unlikely to lower HbA1c in people with type 2 diabetes but may be of benefit for maintaining muscle mass and function and reducing liver fat.


Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells.
Virus-infected cells can be eliminated by cytotoxic T lymphocytes (CTL), which recognize virus-derived peptides bound to major histocompatibility complex (MHC) class I molecules on the cell surface. Until now, this notion has relied on overwhelming but indirect evidence, as the existence of naturally processed viral peptides has not been previously reported. Here we show that such peptides can be extracted from virus-infected cells by acid elution. Both the naturally processed H-2-Db-restricted and H-2-Kd-restricted peptides from influenza nucleoprotein are smaller than the corresponding synthetic peptides, which have first been used to determine the respective CTL epitopes. As with minor histocompatibility antigens, occurrence of viral peptides seems to be heavily dependent on MHC class I molecules, because infected H-2d cells do not contain the H-2-Db-restricted peptide, and infected H-2b cells do not contain the H-2-Kd-restricted peptide. Our data provide direct experimental proof for the above notion on MHC-associated viral peptides on virus-infected cells.


Orlistat-induced bullous leukocytoclastic vasculitis.
Cutaneous leukocytoclastic vasculitis (LCV), also known as small-vessel vasculitis, is a process thought to be related to the presence of circulating immune complexes. Leukocytoclastic vasculitis is thought to be idiopathic in up to 50% of cases, but other common causes and associated disorders include certain medications, most frequently antibiotics; infections; collagen-vascular disease; paraproteinemias; and rarely neoplasia. We report a patient with cutaneous LCV induced by orlistat, a pancreatic lipase inhibitor that works as a weight-loss agent by decreasing the absorption of dietary fat.


Epidemiology and Risk Factors Associated With Mortality in Consecutive Patients With Bacterial Bloodstream Infection: Impact of MDR and XDR Bacteria.
Mortality related to bloodstream infections (BSIs) is high. The epidemiology of BSIs is changing due to the increase in multidrug resistance, and it is unclear whether the presence of multidrug-resistant (MDR) organisms, per se, is an independent risk factor for mortality. Our objectives were, first, to describe the epidemiology and outcome of BSIs and, second, to determine the risk factors associated with mortality among patients with BSI. This research used a single-center retrospective observational study design. Patients were identified through microbiological reports. Data on medical history, clinical condition, bacteria, antimicrobial therapy, and mortality were collected. The primary outcome was crude mortality at 30 days. The relationships between mortality and demographic, clinical, and microbiological variables were analyzed by multivariate analysis. A total of 1049 inpatients were included. MDR bacteria were isolated in 27.83% of patients, where 2.14% corresponded to an extremely drug-resistant (XDR) isolate. The crude mortality rates at days 7, 30, and 90 were 12.11%, 25.17%, and 36.13%, respectively. Pitt score >2, lung and abdomen as site of infection, and XDR Pseudomonas aeruginosa were independent risk factors for 7-, 30-, and 90-day mortality. Charlson score >4, carbapenem-resistant Klebsiella pneumoniae, and XDR Acinetobacter baumannii were independent risk factors for 30- and 90-day mortality. Infection by XDR gram-negative bacteria, Charlson score >4, and immunosuppression were independent risk factors for mortality in patients who were stable at the time of BSI. BSI is an event with an extreme impact on mortality. Patients with severe clinical condition are at higher risk of death. The presence of XDR gram-negative bacteria in blood is strongly and independently associated with patient death.


Migration patterns and phenotypic differentiation of long-term expanded human neural progenitor cells after transplantation into the adult rat brain.
We have examined long-term growth-factor expanded human neural progenitors following transplantation into the adult rat brain. Cells, obtained from the forebrain of a 9-week old fetus, propagated in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory factor were transplanted into the striatum, subventricular zone (SVZ), and hippocampus. At 14 weeks, implanted cells were identified using antisera recognizing human nuclei and the reporter gene green fluorescent protein. Different migration patterns of the grafted cells were observed: (i) target-directed migration of doublecortin (DCX, a marker for migrating neuroblasts)-positive cells along the rostral migratory stream to the olfactory bulb and into the granular cell layer following transplantation into the SVZ and hippocampus, respectively; (ii) non-directed migration of DCX-positive cells in the grey matter in striatum and hippocampus, and (iii) extensive migration of above all nestin-positive/DCX-negative cells within white matter tracts. At the striatal implantation site, neuronal differentiation was most pronounced at the graft core with axonal projections extending along the internal capsule bundles. In the hippocampus, cells differentiated primarily into interneurons both in the dentate gyrus and in the CA1-3 regions as well as into granule-like neurons. In the striatum and hippocampus, a significant proportion of the grafted cells differentiated into glial cells, some with long processes extending along white matter tracts. Although the survival time was over 3 months in the present study a large fraction of the grafted cells remained undifferentiated in a stem or progenitor cell stage as revealed by the expression of nestin and/or GFAP.


Exploratory Bi-factor Analysis.
Bi-factor analysis is a form of confirmatory factor analysis originally introduced by Holzinger. The bi-factor model has a general factor and a number of group factors. The purpose of this paper is to introduce an exploratory form of bi-factor analysis. An advantage of using exploratory bi-factor analysis is that one need not provide a specific bi-factor model a priori. The result of an exploratory bi-factor analysis, however, can be used as an aid in defining a specific bi-factor model. Our exploratory bi-factor analysis is simply exploratory factor analysis using a bi-factor rotation criterion. This is a criterion designed to produce perfect cluster structure in all but the first column of a rotated loading matrix. Examples are given to show how exploratory bi-factor analysis can be used with ideal and real data. The relation of exploratory bi-factor analysis to the Schmid-Leiman method is discussed.


Suspected poisoning of domestic animals by pesticides.
A retrospective study was carried out by reviewing all suspected cases of domestic animal poisoning attributed to pesticides, reported to the Milan Poison Control Centre (MPCC) between January 2011 and December 2013. During this period, pesticides were found to be responsible for 37.3% of all suspected poisoning enquiries received (815). The most commonly species involved was the dog (71.1% of calls) followed by the cat (15.8%), while a limited number of cases involved horses, goats and sheep. Most cases of exposure (47.1%) resulted in mild to moderate clinical signs. The outcome was reported in 59.9% of these cases, with death occurring in 10.4% of them. Insecticides (40.8%) proved to be the most common group of pesticides involved and exposure to pyrethrins-pyrethroids accounted for the majority of calls. According to the MPCC data, there has been a decrease in the number of suspected poisonings cases attributed to pesticides that have been banned by the EU, including aldicarb, carbofuran, endosulfan and paraquat. In contrast, there has been an increase of suspected poisoning cases attributed to the neonicotinoids, imidacloprid and acetamiprid, probably due to their widespread use in recent years. Cases of suspected poisoning that involved exposure to rodenticides accounted for 27.6% of calls received by the MPCC and anticoagulant rodenticides were the primary cause of calls, with many cases involving brodifacoum and bromadiolone. Herbicides were involved in 14.2% of calls related to pesticides and glyphosate was the main culprit in cases involving dogs, cats, horses, goats and sheep. As far as exposure to molluscicides (11.5%) and fungicides (5.9%), most of the cases involved dogs and the suspected poisoning agents were metaldehyde and copper compounds respectively. The data collected are useful in determining trends in poisoning episodes and identifying newly emerging toxicants, thus demonstrating the prevalence of pesticides as causative agents in animal poisonings.


Unconventional CD147-dependent platelet activation elicited by SARS-CoV-2 in COVID-19.
Platelet activation and thrombotic events characterizes COVID-19. To characterize platelet activation and determine if SARS-CoV-2 induces platelet activation. We investigated platelet activation in 119 COVID-19 patients at admission in a university hospital in Milan, Italy, between March 18 and May 5, 2020. Sixty-nine subjects (36 healthy donors, 26 patients with coronary artery disease, coronary artery disease, and seven patients with sepsis) served as controls. COVID-19 patients had activated platelets, as assessed by the expression and distribution of HMGB1 and von Willebrand factor, and by the accumulation of platelet-derived (plt) extracellular vesicles (EVs) and HMGB1+ plt-EVs in the plasma. P-selectin upregulation was not detectable on the platelet surface in a fraction of patients (55%) and the concentration of soluble P-selectin in the plasma was conversely increased. The plasma concentration of HMGB1+ plt-EVs of patients at hospital admission remained in a multivariate analysis an independent predictor of the clinical outcome, as assessed using a 6-point ordinal scale (from 1 = discharged to 6 = death). Platelets interacting in vitro with SARS-CoV-2 underwent activation, which was replicated using SARS-CoV-2 pseudo-viral particles and purified recombinant SARS-CoV-2 spike protein S1 subunits. Human platelets express CD147, a putative coreceptor for SARS-CoV-2, and Spike-dependent platelet activation, aggregation and granule release, release of soluble P-selectin and HMGB1+ plt-EVs abated in the presence of anti-CD147 antibodies. Hence, an early and intense platelet activation, which is reproduced by stimulating platelets in vitro with SARS-CoV-2, characterizes COVID-19 and could contribute to the inflammatory and hemostatic manifestations of the disease.


Experiences of newly hired nurses during the Covid-19 emergency: descriptive qualitative research.
The Covid-19 pandemic led to an increased demand for healthcare professionals, particularly nurses. The Piacenza Local Health Service, Northern Italy, issued several calls for tenders in order to recruit nurses and the University anticipated graduation sessions, so several new graduates nurses found themselves facing their first work experience in the middle of the pandemic emergency. It is well known that being a first-time employee causes stress, but there are few studies yet investigating the perception of newly employed nurses during the pandemic. The aim of this research is therefore to describe the experience of these nurses. A descriptive qualitative study was conducted through interviews. The research was approved by the 'Area Vasta Emilia Nord Ethics Committee. 14 nurses were interviewed and nine themes were found. Emotions, awareness, job opportunities, professional liability, organisational aspects and relationship with the other. Our study shows how stress, anxiety and feelings of inadequacy characterise new nurses' entry into the workplace. Emotional support strategies, such as counselling and emergency preparedness training, could help early career professionals to cope with complex and emotionally charged clinical care situations with greater resilience. ClinicalTrials.gov Identifier: NCT05110859.


Modeling of the Simultaneous Hydrogen Evolution and Cobalt Electrodeposition.
A mathematical model of simultaneous cobalt deposition and hydrogen evolution was developed and applied to the electroreduction process of 5 mM Co2+ ions investigated by cyclic voltammetry (CV) technique at different hydrogen ion concentrations (pH=2, 3, 4). The kinetic parameters of such a complex process were determined, and the validity of the model and its sensitivity to changes in individual parameters were verified. The relative value of the approximate standard deviation (ASD% ) was used to determine the degree of fit of the model to the experimental data. The catalytic effect of cobalt on the hydrogen evolution process was comprehensively confirmed.


[Impact of huolong moxibustion on TNF-α and pain degree in the patients of discogenic low back pain].
To discuss the impact of huolong moxibustion on pain degree in the patients of discogenic low back pain and the effect mechanism. Sixty-five patients were randomized into an observation group (33 cases) and a control group (32 cases). In the observation group, huolong moxibustion was applied along the distribution of the Governor Vessel, once a day. In the control group, the routine traction combined with massage therapy was adopted, once a day. In the two groups, the treatment was given 6 times a week, at interval of 1 day. In 3 weeks of treatment, pain score and serum tumor necrosis factor α (TNF-α) level were compared with those before treatment in the two groups. Compared with those before treatment, pain score and TNF-α level were reduced significantly after treatment in the two groups (both P < 0.05). The results in the observation group were lower than those in the control group (pain score: 1.95 ± 0.61 vs 2.11 ± 0.61; TNF-α: (1.33 ± 0.30) nmol/L vs (1.55 ± 0.48) nmol/L, (both P < 0.05). Huolong moxibustion significantly alleviates pain in the patients of discogenic low back pain and its effect mechanism is possibly relevant with TNF-α reducing.


Pulmonary mycobacterial disease: diagnostic performance of low-dose digital tomosynthesis as compared with chest radiography.
To compare the diagnostic performance of a low-radiation-dose digital tomosynthesis (DTS) technique with that of conventional radiography in the detection of lung lesions in patients with pulmonary mycobacterial disease. The institutional review board approved this study, and all patients provided informed consent. In this study, 100 patients (65 study patients, 35 control patients) underwent multidetector computed tomography (CT), chest radiography, and low-dose DTS (effective doses: 3.4, 0.02, and 0.05 mSv, respectively). Two radiologists evaluated radiographs and DTS images for the presence of parenchymal lesions and the number of cavities in each patient; CT served as the reference standard. Wilcoxon signed rank and McNemar tests and κ statistics were used. The accuracies of DTS and radiography in depicting mycobacterial disease were 97% and 89%, respectively, for observer 1 (P = .039) and 99% and 93%, respectively, for observer 2 (P = .031). The accuracies of DTS and radiography in depicting each lesion type were, respectively, 95% and 77% for bronchiolitis, 92% and 76% for nodules, 86% and 79% for consolidation, and 93% and 70% for cavities. Interobserver agreement with DTS (κ = 0.62-0.94) was superior to that with radiography (κ = 0.46-0.62). Of a total of 141 cavities found with CT, means of 27 (19%) cavities at chest radiography and 108 (77%) cavities at DTS (P < .01) were detected by the two observers. DTS performed with a low-dose technique is superior to radiography for the detection of lung lesions in patients with pulmonary mycobacterial disease.


Histopathologic evaluation of scrotal skin biopsy supporting the diagnosis of Bechet's disease.
Bechet's disease is a multisystemic inflammatory disease of unknown causes, characterized by painful oral and genitalia ulcers, eye involvement, and other systemic manifestation. Bechet's disease is a clinical diagnosis with no specific laboratory test and rarely encountered in urological practices. Here, we are reporting a case of Bechet's diseases in a patient who presented with painful scrotal ulcers underwent examination under anesthesia to role out scrotal abscess and histopathology evaluation of scrotal skin biopsy supporting the diagnosis of Bechet's disease.


Relationship between several markers and presence of metabolic syndrome or components of the metabolic syndrome in Japanese workers.
The reported associations between metabolic syndrome (MetS) and systemic vascular inflammation/insulin resistance prompted the author to determine the predictive ability of markers for MetS in the occupational field. The study was performed in 3460 working men aged 30 to 64 years. The author measured the serum levels of high-sensitivity C-reactive protein and insulin as potential key biomarkers of MetS. Multivariate analysis revealed significant associations between the presence of MetS and the log-transformed value of serum insulin and log-transformed value of serum C-reactive protein, with odds ratios of 29.4 (95% confidence interval, 18.0 to 48.2; P < 0.001) and 1.87 (95% confidence interval, 1.47 to 2.38; P < 0.001) of these two markers, respectively, for the presence of MetS. Elevated serum levels of insulin were found to be strongly associated with MetS in this cross-sectional study.


Radioembolization with Yttrium-90 Microspheres for the Treatment of Liver Metastases of Pancreatic Adenocarcinoma: A Multicenter Analysis.
To retrospectively assess the efficacy and safety of radioembolization with yttrium-90 (90Y) resin microspheres as a second-line option in patients with liver metastases from pancreatic adenocarcinoma. Thirty-three patients with metastatic pancreatic adenocarcinoma that progressed despite systemic chemotherapy and other treatments directed at primary tumors and metastases were treated with 90Y radioembolization at 1 of 3 institutions from 2011 through 2017. Data from laboratory and imaging studies at 2, 4, 8, and 12 weeks after treatment were analyzed. Tumor response was assessed with Response Evaluation Criteria In Solid Tumors version 1.1 and adverse events with Common Terminology Criteria for Adverse Events version 4.0. Imaging results showed partial response in 8 patients (42%), stable disease in 7 (37%), and progressive disease in 4 (21%). Median overall survival times after radioembolization and diagnosis of the primary tumor were 8.1 (95% CI, 4.8-12.5) and 20.8 (95% CI, 14.2-29.0) months, respectively. Radioembolization did not produce major hepatic toxicity, and changes in liver enzyme levels were rarely grade ≥ 3 during the 12-week follow-up. The exceptions were 3 patients with grade 3 increased alkaline phosphatase (week 2) and bilirubin levels (week 4), increased bilirubin level (week 12), and decreased albumin level (week 12), respectively. Most reported complications were grade ≤ 2, with 2 patients showing short-term radioembolization-related grade 3 abdominal distention, abdominal pain, fatigue, or ascites. Yttrium-90 radioembolization provided a meaningful survival benefit in patients with liver metastases from pancreatic adenocarcinoma that progressed despite previous therapies. Adverse events and liver toxicity were tolerable and only occasionally severe (grade ≥ 3).


Analysis of tryptic digests of bovine beta-casein by reversed-phase high-performance liquid chromatography.
Reversed-phase high-performance liquid chromatography (RP-HPLC) was used to separate the tryptic peptides of beta-casein. A gradient of 0-50% acetonitrile in 0.1% trifluoroacetic acid at a flow-rate of 0.8 ml/min resolved ten of the thirteen peptides. A modified gradient resolved the three peptides eluted at ca. 25% acetonitrile. RP-HPLC proved superior to high-voltage paper electrophoresis in analysis time, resolution and flexibility. The methods developed for the analysis of proteolysis of the milk protein, beta-casein, are now being applied to study the action of extracellular proteases from dairy bacteria on milk proteins.


Competition, differential mortality, and their effect on the spatial pattern of a desert perennial, Eriogonum inflatum Torr and Frem (Polygonaceae).
Eriogonum inflatum Torr and Frém. (Polygonaceae) experiences unusually high population turnover for a desert perennial. For example, 20% of the individuals in the study population were dead but still rooted. Pairs of nearest neighbors which included one dead individual tended to be closer to one another than pairs of live nearest neighbors. Thus, deaths are nonrandom. Individuals which are too close to one another are most vulnerable. Nevertheless, the deaths of 20% of the individuals had no effect on the intensity of the spatial pattern of the population; survivors were just as highly aggregated as survivors and dead individuals together. I conclude that competitor-induced mortality will not have predictable effects on the spatial pattern of plant populations which consist of a mosaic of individuals of different ages and sizes.


Long-term treatment with calcitriol (1,25(OH)2 vit D3) retards a biomarker of hippocampal aging in rats.
Based on a literature implicating altered calcium homeostasis in brain aging and Alzheimer's Disease (AD) and evidence of decreased vitamin D action in AD subjects, the possibility was tested that calcitriol (1,25(OH)2 vitamin D3), the active form of vitamin D3, might reduce markers of brain aging in rats. Animals were treated 5x weekly for prolonged periods (6-12 months) with either calcitriol in doses sufficient to elevate serum calcium and phosphate (20 ng/rat), calcitonin (1.5 IU/rat) or vehicle, in three separate long-term experiments on aging rats. New stereological methods (physical disector) of cell counting were used to evaluate neuronal density, a reliable biomarker of hippocampal aging in rats. In two experiments utilizing Brown-Norway x F344 hybrid rats (BN x F344), 8 months and 12 months of chronic treatment with calcitriol resulted in a higher density of CA1 neurons in the middle regions of the hippocampus, compared to vehicle or calcitonin treatment. However, one study with aging F344 rats was terminated early because of extensive strain-specific pathology and no effect of calcitriol on neuronal density was observed. These studies suggest that, under some conditions, hormonal treatments that regulate calcium homeostasis can modulate markers of brain aging.


Theoretical investigation on the adsorption configuration and (•)OH-initiated photocatalytic degradation mechanism of typical atmospheric VOCs styrene onto (TiO2)n clusters.
In this study, the adsorption mechanism and hydroxyl radical ((•)OH)-initiated photocatalytic degradation mechanism of styrene onto different (TiO2)n clusters were investigated using density functional theory. Styrene, a typical model atmospheric volatile organic compound (VOC), was found to be readily adsorbed onto (TiO2)n clusters through its vinyl group with strong chemisorption. This suggests that (TiO2)n clusters (sub 1 nm) are able to effectively adsorb and trap styrene. Adsorbed styrene is then easily attacked by (•)OH to form a series of vinyl-OH-adducts. Conversely, phenyl-OH-adducts and H-abstraction products are very difficult to form in this system. Kinetics calculations using canonical variational transition state theory show that temperature has little effect on the rate constants during photocatalytic degradation process. The presence of TiO2 does not change the degradation mechanism of styrene, but can accelerate its photocatalyic degradation rate, and the rate will increase as TiO2 cluster size increases; as such, the TiO2 nano-clusters catalyst should have the photocatalytic ability to effectively degrade styrene. This theory-based study offers insights into the catalytic effect of TiO2 catalyst and the photocatalytic degradation mechanism of benzene series air pollutants at the molecular level.


Acquired hemophilia A developing in the perioperative period of pancreatoduodenectomy: a report of two cases.
Acquired hemophilia A (AHA) is a rare disease characterized by a prolonged activated partial thromboplastin time (aPTT) and the production of coagulation factor VIII inhibitors. We encountered two cases of AHA in the perioperative period of pancreatoduodenectomy (PD). Case 1: A 76-year-old woman with intraductal papillary mucinous carcinoma developed acute cholecystitis 5 days before PD. Despite immediate improvement in her acute cholecystitis with biliary drainage and antibiotics, her aPTT level was prolonged (55.9 s). PD was performed as scheduled. On postoperative day (POD) 2, she developed intra-abdominal hemorrhaging that required reoperation. However, intra-abdominal bleeding and concomitant anemia persisted after reoperation. On POD 13, she was diagnosed with AHA based on the detection of an inhibitor of coagulation factor VIII. Despite hemostatic and immunosuppressive treatment, including massive blood transfusion, her general condition gradually worsened due to continuous bleeding and secondary infections. She ultimately died of multiple organ failure on POD 71. Case 2: An 82-year-old man received PD for distal cholangiocarcinoma. On POD 3, a small amount of blood via abdominal drainage was observed. On POD 4, his aPTT level was prolonged (61.5 s). On POD 8, subcutaneous hemorrhaging of the median wound was observed, and corticosteroids were administered under suspicion of AHA on POD 9. On POD 15, an inhibitor of FVIII was detected, and he was diagnosed with AHA. On POD 17, the aPTT level had normalized, and an inhibitor of FVIII was undetectable. On POD 41, he was discharged without any serious hemorrhagic events. AHA may be more frequent than previously reported. When unexplained prolonged aPTT or bleeding symptoms are observed, it is important to keep AHA in mind during the perioperative period of invasive surgery.


Giant energy-storage density with ultrahigh efficiency in lead-free relaxors via high-entropy design.
Next-generation advanced high/pulsed power capacitors rely heavily on dielectric ceramics with high energy storage performance. However, thus far, the huge challenge of realizing ultrahigh recoverable energy storage density (Wrec) accompanied by ultrahigh efficiency (η) still existed and has become a key bottleneck restricting the development of dielectric materials in cutting-edge energy storage applications. Here, we propose a high-entropy strategy to design "local polymorphic distortion" including rhombohedral-orthorhombic-tetragonal-cubic multiphase nanoclusters and random oxygen octahedral tilt, resulting in ultrasmall polar nanoregions, an enhanced breakdown electric field, and delayed polarization saturation. A giant Wrec ~10.06 J cm-3 is realized in lead-free relaxor ferroelectrics, especially with an ultrahigh η ~90.8%, showing breakthrough progress in the comprehensive energy storage performance for lead-free bulk ceramics. This work opens up an effective avenue to design dielectric materials with ultrahigh comprehensive energy storage performance to meet the demanding requirements of advanced energy storage applications.


Long-distance movement of helical multipartite phytoviruses: keep connected or die?
All living organisms have to preserve genome integrity to ensure the survival of progeny generations. Viruses, though often regarded as 'non living', protect their nucleic acids from biotic and abiotic stresses, ranging from nuclease action to radiation-induced adducts. When the viral genome is split into multiple segments, preservation of at least one copy of each segment is required. While segmented and monopartite viruses use an all-in-one strategy, multipartite viruses have to address in the cell at least one of each viral particle in which the split positive stranded RNA genome is individually packaged. Here, we review and discuss the biology of multipartite helical RNA phytoviruses to outline our current hypothesis on a coordinated genomic RNA network RNP complex that preserves an all-in-one strategy and genome integrity.


Quantitative structure-activity relationships for small non-peptide antagonists of CXCR2: indirect 3D approach using the frontal polygon method.
The chemokine receptor, CXCR2, plays an important role in recruiting granulocytes to sites of inflammation and has been proposed as an important therapeutic target. A number of CXCR2 antagonists have been synthesized and evaluated; however, quantitative structure-activity relationship (QSAR) models have not been developed for these molecules. Most CXCR2 antagonists can be grouped into four related categories: N,N'-diphenylureas, nicotinamide N-oxides, quinoxalines, and triazolethiols. Based on these categories, we developed a QSAR model for 59 nonpeptide antagonists of CXCR2 using a partial 3D comparison of the antagonists with local fingerprints obtained from rigid and flexible fragments of the molecules. Each compound was represented by calculated structural descriptors that encoded atomic charge, molar refraction, hydrophobicity, and geometric features. We obtained good conventional R(2) coefficients, high leave-one-out cross-validated values for the whole dataset (R(cv)(2)=0.785), as well as for the dataset divided into subsets of triazolethiol derivatives (R(cv)(2)=0.821) and joint subset of N'-diphenylureas, nicotinamide N-oxides, N,N'-diphenylureas, and quinoxaline derivatives and quinoxalines derivatives (R(cv)(2)=0.766), indicating a good predictive ability and robustness of the model. Additionally, charge distribution was found to be a significant contributor in modeling whole dataset. Using our model, structural fragments (submolecules) responsible for the antagonist activity were also identified. These data suggest the QSAR models developed here may be useful in guiding the design of CXCR2 antagonists from molecular fragments.


Earlier Tracheostomy Reduces Complications in Complete Cervical Spinal Cord Injury in Real-World Practice: Analysis of a Multicenter Cohort of 2001 Patients.
It is believed that early tracheostomy in patients with traumatic cervical spinal cord injury (SCI) may lessen the risk of developing complications and reduce the duration of mechanical ventilation and critical care stay. This study aims to assess whether early tracheostomy is beneficial in patients with traumatic cervical SCI. We conducted a retrospective cohort study using data from the American College of Surgeons Trauma Quality Improvement Program database from 2010 to 2018. Adult patients with a diagnosis of acute complete (ASIA A) traumatic cervical SCI who underwent surgery and tracheostomy were included. Patients were stratified into those receiving early (at or before 7 days) and delayed tracheostomy. Propensity score matching was used to assess the association between delayed tracheostomy and the risk of in-hospital adverse events. Risk-adjusted variability in tracheostomy timing across trauma centers was investigated using mixed-effects regression. The study included 2001 patients from 374 North American trauma centers. The median time to tracheostomy was 9.2 days (IQR: 6.1-13.1 days), with 654 patients (32.7%) undergoing early tracheostomy. After matching, the odds of a major complication were significantly lower for early tracheostomy patients (OR: .90; 95% CI: .88-.98). Patients were also significantly less likely to experience an immobility-related complication (OR: .90; 95% CI: .88-.98). Patients in the early group spent 8.2 fewer days in the critical care unit (95% CI: -10.2 to -6.61) and 6.7 fewer days ventilated (95% CI: -9.44 to -5.23). There was significant variability in tracheostomy timeliness between trauma centers with a median odds ratio of 12.2 (95% CI: 9.7-13.7), which was not explained by case-mix and hospital-level characteristics. A 7-day threshold to implement tracheostomy seems to be associated with reduced in-hospital complications, time in the critical care unit, and time on mechanical ventilation.


Bilirubin oxidation products (BOXes): synthesis, stability and chemical characteristics.
Bilirubin oxidation products (BOXes) have been a subject of interest in neurosurgery because they are purported to be involved in subarachnoid hemorrhage induced cerebral vasospasm. There is a growing body of information concerning their putative role in vasospasm; however, there is a dearth of information concerning the chemical and biochemical characteristics of BOXes. A clearer understanding of the synthesis, stability and characteristics of BOXes will be important for a better understanding of the role of BOXes post subarachnoid hemorrhage. We used hydrogen peroxide to oxidize bilirubin and produce BOXes. BOXes were extracted and analyzed using conventional methods such as HPLC and mass spectrometry. Characterization of the stability of BOXes demonstrates that light can photodegrade BOXes with a t1/2 of up to 10h depending upon conditions. Mixed isomers of BOXes have an apparent extinction coefficient of epsilon = 6985, and a lambda(max) of 310 nm. BOXes are produced by the oxidation of bilirubin, yielding a mixture of isomers: 4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide (BOX A) and 3-methyl-5-oxo-4-vinyl-(1,5-dihydropyrrol-2-ylide-ne)acetamide (BOX B). The BOXes are photodegraded by ambient light and can be analyzed spectrophotometrically with their extinction coefficient as well as with HPLC or mass spectrometry. Their small molecular weight and photodegradation may have made them difficult to characterize in previous studies.