The relationship between the perfusion deficit, infarct size and time after experimental coronary artery occlusion.
It is well known that coronary occlusions of short duration do not produce infarcts in the dog heart, but permanent occlusions always do. The aim of this paper was to investigate with quantitative direct measurements the determinants of infarct size within these two extremes. We measured left ventricular MV2, coronary and collateral blood flow and infarct size after occlusion times varying between 45 minutes and 24 hours. MVO2 was kept low in one group by establishing low heart rates with a synthetic opiate. In another group, MV2 was kept elevated by giving synthetic catecholamines (dobutamine) that stimulated contractility and heart rate. Under the described experimental conditions LV-coronary blood flow reflected the true demand for blood and oxygen. The ratio of collateral blood flow over coronary blood flow (both measured with tracer microspheres) was therefore a good approximation of the supply-demand ratio (SD). Since collateral flow was inhomogeneously distributed across the left ventricular wall, the SD-ratio showed similar variations. As the collateral blood flow increased with elapsed time after coronary occlusion, the SD-ratio improved. Since high LV-O2-demand increased coronary flow but exerted practically no influence on collateral flow, this situation influenced the SD-ratio in a negative way. Decreased O2-demand had the opposite effect. The SD-ratio is thus a valid expression of the relative and absolute blood flow deficit as influenced by the local and general O2-demand. We found significant and characteristic correlations between the SD-ratio and infarct which was only influenced by time. A blood flow deficit of 90% (i.e., collateral flow = 10% of required flow) produced a 50%-infarct (relative to the risk-region) with a 45-min occlusion but a 90%-infarct with occlusion times of 3 hrs and longer. If the perfusion deficit is only 0.5 (collateral flow = 50% of required flow), no infarct is detectable at occlusion times shorter than 3 hrs. Small perfusion deficits of only 20% below required flow caused infarctions at 24 hrs and longer. In the group where the SD-ratio was closer to unity because of a low overall LV-O2-consumption (bradycardia), infarcts at t = 24 hrs were significantly smaller than in the group with a high LV-MVO2.


Perception of recently graduated Dutch dentists of their education.
The curriculum of the three dental schools in the Netherlands consists of a three-year bachelor's and three-year master's course. The education programmes focus inter alia on clinical dental reasoning, thinking and acting scientifically, general oral healthcare activities, and communication and (inter)professional cooperation. This study examined how recently graduated dentists, in the light of their work experience, evaluate their education in retrospect. All 1074 dentists who graduated between 2012 and mid-2017 were invited by e-mail to answer a web survey. Of those, 314 (29%) took part in the study. The majority of dentists were positive about their knowledge of general and clinical oral healthcare fields when they graduated (70% and 68%, respectively). Fewer dentists were satisfied with their skills in terms of some specific procedures (50%) and clinical professional areas (33%). By far, the majority (85%) were satisfied with the educational skills of their teachers. The majority (70%) felt that their education fitted in well with their professional practice. Nevertheless, 60% thought a year's trainee work experience would be a good idea. The overall evaluation of dentists who have their own practices was less positive than those who do not. Knowledge and skills relating to managing a practice were not sufficiently addressed in the programme. The introduction of a practical internship would be desirable, preferably during the education. But when they look back, the majority of recently graduated dentists in the Netherlands are generally positive about the education they received.


Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells.
Loss of alveolar type 2 cells (AEC2s) and the ectopic appearance of basal cells in the alveoli characterize severe lung injuries such as idiopathic pulmonary fibrosis (IPF). Here we demonstrate that human alveolar type 2 cells (hAEC2s), unlike murine AEC2s, transdifferentiate into basal cells in response to fibrotic signalling in the lung mesenchyme, in vitro and in vivo. Single-cell analysis of normal hAEC2s and mesenchymal cells in organoid co-cultures revealed the emergence of pathologic fibroblasts and basaloid cells previously described in IPF. Transforming growth factor-β1 and anti-bone morphogenic protein signalling in the organoids promoted transdifferentiation. Trajectory and histologic analyses of both hAEC2-derived organoids and IPF epithelium indicated that hAEC2s transdifferentiate into basal cells through alveolar-basal intermediates that accumulate in proximity to pathologic CTHRC1hi/TGFB1hi fibroblasts. Our study indicates that hAEC2 loss and expansion of alveolar metaplastic basal cells in severe human lung injuries are causally connected through an hAEC2-basal cell lineage trajectory driven by aberrant mesenchyme.


Removal of dental implants displaced into the maxillary sinus: a retrospective single-center study.
The use of dental implants in the prosthetic rehabilitation of the posterior atrophic maxilla might be a challenge procedure because of low bone quantity and quality. This study aimed to report cases of implant displacement or migration into the maxillary sinus treated from 2008 to 2021. All patients with unintentional insertion and/or displacement of dental implants into the maxillary sinus cavity that underwent surgical removal were included. Variables assessed included the patients' characteristics, past medical history, clinical and radiological findings at presentation, surgical approach (transoral, transnasal, combined), and outcome. A total of forty patients (23 male, 17 female) underwent surgical removal of dental implant displaced in the maxillary sinus. The mean age was 52,3 + 11,3 years. Seven patients presented with oro-antral fistula (OAF). In 15 cases, an ostium obstruction was diagnosed. Twenty-five patients underwent transoral surgery under local anesthesia. Eleven patients were treated solely via transnasal endoscopic approach, and four patients who had an associated OAF underwent surgery through a combined transnasal and transoral approach. All patients healed uneventfully without complications. These results and recent literature validate that transoral and transnasal approach, or a combination of these procedures, can be used safely to treat complications following displacement/migration of dental implants in the maxillary sinus. Early surgical removal minimizes sinus inflammation and prevents more invasive procedures. Each procedure presents specific indications that must be carefully evaluated prior to treatment choice to optimize intervention outcomes.


Energy allocation changes in overwintering adults of the common pistachio Psylla, Agonoscena pistaciae Burckhardt & Lauterer (Hemiptera: Psyllidae).
The common pistachio psylla, Agonoscena pistaciae Burckhardt & Lauterer (Hemiptera: Psyllidae), is known as the key pest of pistachio orchards in Iran. This pest passes the winter as adults. In this study, energy allocation changes in relation to ambient temperature were investigated in field-collected adults by measuring total body sugar, trehalose, glucose, sorbitol, myoinositol, glycogen, lipid, and protein contents. Glycogen content decreased with decrease in ambient temperature. The decrease in glycogen content was proportional to the increase in total body sugar, trehalose, myoinositol, and sorbitol contents. In January, with mean ambient temperature of 5.4°C, glycogen content was at the lowest level, whereas total body sugar, trehalose, glucose, and sorbitol were at the highest level. Total body sugar, trehalose, myoinositol, and sorbitol contents increased as temperature decreased from 22.7°C in October to 5.4°C in January. In conclusion, low molecular weight carbohydrates and polyols may play a role in winter survival and adaptation to cold of the common pistachio psylla by providing the required cryoprotection. Also, overwintering adults of the common pistachio psylla may store energy in the form of lipid for later utilization during the overwintering.


Pharmacological modification of oxygen affinity improves deformability of deoxygenated sickle erythrocytes: a possible therapeutic approach to sickle cell disease.
1. The formation of polymerized haemoglobin S in sickle cells is critically dependent on the concentration of deoxygenated haemoglobin so that compounds which increase the oxygen affinity of haemoglobin S are potential anti-sickling agents. 2. BW12C [5-(2-formyl-3-hydroxyphenoxy)pentanoic acid] and BWA589C [4-(2-formyl-3-hydroxyphenoxymethyl)benzoic acid] are aromatic benzaldehydes that cause a dose-dependent left-shift of the oxygen saturation curve of haemoglobin S by stabilization of its oxy-(R)-conformation. 3. A 5 micron pore filtration method, which is highly sensitive to polymerization of haemoglobin S, was used to demonstrate a significant improvement in the deformability of deoxygenated sickle erythrocytes at concentrations (0.75-1.5 mmol/l] of BW12C and BWA589C that are achievable in vivo. Both compounds may therefore be of value for the treatment of sickle cell disease. 4. Filtration of sickle cells through pores of 5 microns diameter is a sensitive technique for evaluating the rheological effects of potential anti-sickling compounds.


Mechanistic considerations and biomarkers level in nickel-induced neurodegenerative diseases: An updated systematic review.
The environment has been implicated to be a strong determinant of brain health with higher risk of neurodegeneration. The drastic rise in the prevalence of neurodegenerative diseases (NDDs) including Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), multiple sclerosis (MS) etc., supports the idea that environmental factors may play a major role in NDDs aetiology. Nickel is one of the listed environmental metals reported to pose a serious threat to human health. This paper reported available studies on nickel level in NDDs covering both animal and human studies. Different databases were searched for articles reporting the main neurotoxicity mechanisms and the concentration of nickel in fluids and tissues of NDDs patients compared to controls. Data were extracted and synthesized by ensuring the articles were related to nickel and NDDs. Various mechanisms were reported as oxidative stress, disturbances in mitochondrial membrane potential, trace elements homeostasis destabilization, etc. Nickel was found elevated in biological fluids as blood, serum/plasma and CSF and in the brain of NDDs, as a consequence of unintentional exposure thorough nickel-contaminated air, food, water, and skin contact. In addition, after exposure to nickel, the concentration of markers of lipid peroxidation were increased, while some antioxidant defence systems decreased. Thus, the reduction in the exposure to nickel contaminant may hold a promise in reducing the incidence of NDDs.


Instillation of coarse ash particulate matter and lipopolysaccharide produces a systemic inflammatory response in mice.
Coronary ischemic events increase significantly following a "bad air" day. Ambient particulate matter (PM10) is the pollutant most strongly associated with these events. PM10 produces inflammatory injury to the lower airways. It is not clear, however, whether pulmonary inflammation translates to a systemic response. Lipopolysaccharide (LPS) is a proinflammatory molecule often associated with the coarse fraction of PM. It was hypothesized that PM>2.5 from coal plus LPS induce pulmonary inflammation leading to a systemic inflammatory response. Mice were intratracheally instilled with saline, PM (200 microg), PM + LPS10 (PM + 10 microg LPS), or PM + LPS100 (PM + 100 microg LPS). Eighteen hours later, histologic analysis was performed on lungs from each group. Pulmonary and systemic inflammation were assessed by measuring the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in the pulmonary supernatant and plasma. In a follow-up study, the effects of LPS alone were assessed. Histologic analysis revealed a dose-dependent elevation in pulmonary inflammation with all treatments. Pulmonary TNF-alpha and IL-6 both increased significantly with PM + LPS100 treatment. Regarding plasma, TNF-alpha significantly increased in both PM + LPS10 and PM + LPS100 treatments. For plasma IL-6, all groups tended to rise with a significant increase in the PM + LPS100 group. The results of the follow-up study indicate that the responses to PM + LPS were not due to LPS alone. These results suggest that coarse coal fly ash PM>2.5 combined with LPS produced pulmonary and systemic inflammatory responses. The resulting low-level systemic inflammation may contribute to the increased severity of ischemic heart disease observed immediately following a bad air day.


Stimulus avoidance and perceptual adaptation: a vicious cycle paradigm?
Restricting the encountered range of stimuli on a particular stimulus dimension changes a person's perceptual frame of reference, or adaptation level, for such stimuli. The present experiment explores the effect of stimulus avoidance on perceptual adaptation and subsequent avoidance. Results converge with previous findings to indicate that avoidance of danger signals reduces perceptual adaptation level for those signals. In the present experiment, subjects first avoided high-pitched danger-signal tones, thus restricting the range of tone stimuli they encountered, and subsequently overestimated the pitches of low-pitched safety-signal tones. They consequently avoided the low tones as if they were high-pitched danger signals. Perceptual adaptation was evident in subjects' tone pitch ratings only if they had rated the tones throughout their avoidance trials.


A developmentally modified neurone-specific marker in rodent cerebellum.
Out of several monoclonal antibodies secreted by hybridomas resulting from the fusion of a mouse myeloma cell line with spleen cells from mice immunized with cerebellar membranes from 12 day old rats, one, called 11.9, produced an unusual immunolabelling pattern when tested on sections of rat cerebellum. The cerebellar distribution of the antigenic sites recognized by this antibody using an immunoperoxidase technique at the optical and ultrastructural levels is described in detail in this report. The immunoreaction product was found in the adult rat to be associated with the microtubules and the zone immediately beneath the plasma membrane of parallel fibres. In young animals the density of immunostaining appears to be higher than in the adult, and the staining is detectable in addition in the perikaryal cytoplasm of granule cells. Biochemical studies using the Western immunoblot technique demonstrate that the antigens consist of two polypeptides of molecular weights 120 and 185 kD. The possible relation of the antigens to cytoskeletal structures is discussed and the labelling pattern is compared with that produced by other known monoclonal antibodies.


β-Carotene regulates glucose transport and insulin resistance in gestational diabetes mellitus by increasing the expression of SHBG.
The aim of this work was to study the effect and mechanism of β-carotene on insulin resistance and glucose transport in gestational diabetes mellitus (GDM). Placental tissue and venous blood of 26 GDM patients and 18 normal women were collected. Mice fed a high-fat diet were established as GDM models and treated with β-carotene, from which peripheral blood and placenta tissue were collected. HTR-8/SVneo cells were treated with 10-7 mol/L insulin for 48 h and established as insulin resistance cell models. The expression of SHBG, GLUT1, GLUT3, GLUT4, IRS-1, IRS-2, PI3Kp85α, and p-CREB/CREB in placental tissues and HTR-8/SVneo cells was detected. Insulin resistance index was calculated from the values of fasting blood glucose and fasting insulin. The glucose consumption of insulin-resistant cells was calculated by detecting the glucose content of the supernatant. The cyclic adenosine monophosphate (cAMP) kit was applied to measure the concentration of cAMP in cells. SHBG was lowly expressed in GDM. β-Carotene treatment upregulated SHBG in the placenta of GDM mice and in insulin-resistant HTR-8/SVneo cells. Overexpression of SHBG upregulated GLUT3, GLUT4, and IRS-1 and enhanced glucose consumption in insulin-resistant cells. β-Carotene treatment promoted the expression of SHBG, GLUT4 and IRS-1 and increased glucose consumption in insulin-resistant cells underexpressing SHBG. Silencing of SHBG decreased the levels of cAMP and pCREB/CREB but β-carotene treatment increased their expression despite SHBG silencing in insulin-resistant cells. β-Carotene promotes glucose transport and inhibits insulin resistance in GDM by increasing the expression of SHBG.


Lead and sudden infant death. Investigations on blood samples of SID babies.
To investigate a potential relationship between an elevated lead burden and sudden infant death (SID), the lead concentrations (Pb-B) were determined in 41 blood samples from SID babies and compared with the Pb-B of 5 babies who died traumatically and 77 living control babies. Several factors that may influence the Pb-B were taken into consideration, especially a dependence of the Pb-B on age and social class. Moreover, a post-mortem water shift occurs in the blood. Even taking these factors into consideration the distribution of the Pb-B's of the SID group was found to differ on a highly significant level (greater than 99.9%) from the control group. Five Pb-B's of the SID group were higher than the highest lead concentration found in blood from the control babies. Negative influences of lead on the pre- and postnatal maturation of the brain are discussed in the search for a possible causal connection between an elevated lead burden and the occurrence of SID.


Intimate partner violence and its association with women's reproductive health in Pakistan.
To determine the prevalence of intimate partner violence in Pakistan and its association with reproductive health outcomes. A cross-sectional survey was conducted in 8 hospitals in Lahore and Sialkot between October 2008 and January 2009. Information from randomly selected ever-married women of reproductive age was collected via a structured interview. Psychologic, physical, and sexual violence was categorized as "no" or "severe" violence. Associations between reproductive health outcomes and violence were assessed by multivariate logistic regression. Among 373 women interviewed, 75.9% reported severe psychologic, 34.6% reported severe sexual, and 31.9% reported severe physical violence at least once in marital life. Women who experienced severe physical violence were more likely to have their husband's noncooperation in using contraceptives (adjusted odds ratio [AOR], 3.31; 95% confidence interval [CI], 1.93-5.68), poor prenatal care (AOR, 2.11; 95% CI, 1.23-3.69), unplanned pregnancies (AOR, 2.29; 95% CI, 1.39-3.76), and poor self-reported reproductive health (AOR, 2.95; 95% CI, 1.71-4.91) as compared with non-abused women. Similar associations existed for other types of violence. The results highlight the magnitude of violence and its association with reproductive health of women. Urgent action is needed to mitigate the violence and its consequential damage to health.


The effect of cromakalim on the smooth muscle of the guinea-pig urinary bladder.
1. The actions of cromakalim were studied on the detrusor muscle from guinea-pig urinary bladder. Cromakalim reduced the frequency and amplitude of spontaneous contractile activity of the smooth muscle of the guinea-pig urinary bladder at 5 x 10(-8)M and abolished the activity at concentrations above 5 x 10(-7)M. 2. Electrophysiological experiments demonstrated that cromakalim increased membrane conductance, caused a dose-dependent hyperpolarization of the cell membrane and loss of spike activity. These events are consistent with the opening of K+ channels. 3. The effects of 10(-6)M and 10(-5)M cromakalim on the contractile responses to carbachol, potassium and transmural nerve stimulation were studied. Cromakalim did not prevent the detrusor from responding to these agents, although it significantly reduced the contractile response to K+ at concentrations below 70 mM. 4. Uptake and efflux experiments using 86Rb+ were unable to demonstrate any significant effect on transmembrane movement produced by cromakalim (10(-5)M). 5. 43K+ efflux showed a dose-dependent increase in the rate constant on addition of cromakalim. The difference in the selectivity for K+ over Rb+ was confirmed in dual label uptake experiments. 6. Substitution experiments in which the K+ ions in the tissue were gradually replaced by Rb+ demonstrated that cromakalim had a progressively decreasing effect on spontaneous activity as internal K+ was lowered. When all the K+ was replaced by Rb+, cromakalim no longer inhibited spontaneous activity, confirming that the channel opened by cromakalim appears relatively impermeant to Rb+.


Rectorrhagia revealing colonic metastasis from an ovarian primary, an exceptional case report.
Ovarian cancer is a gynecological cancer with a very poor prognosis despite the improvement of therapeutic means, of which metastases at the colic level are exceptional. We report an exceptional case which makes it possible to enrich the poor literature published on the subject. Through this article, we present a very rare case of colonic metastases from ovarian cancer. Biological monitoring and rectal bleeding allowed this rare secondary location to be discovered. Resection then anastomosis allowed our patient to heal. The objectives of this work are threefold: i), to report this very rare case ovarian metastasis ii), to highlight nulliparity as a risk factor in our patient iii), to report that our therapeutic management interrupted and delayed because of COVID 19. Our case report shows that we have to take into consideration this very rare presentation and this even in the absence of true clinical sign. Our work reported also another case of colonic metastasis of a primary ovarian in the very rare case described in the literature and emphasizes the importance of surgical management.


Correction to: Striatal-frontal network activation during voluntary task selection under conditions of monetary reward.
Conflict of interest statement: Although co-author Marie T. Banich is the Editor-in-Chief of Cognitive, Affective, and Behavioral Neuroscience, Stan Floresco served as the action editor for this manuscript.


New insight on interfacial charge transfer at graphitic carbon nitride/sodium niobate heterojunction under piezoelectric effect for the generation of reactive oxygen species.
Piezocatalytic removal of metronidazole (MET) using graphitic carbon nitride (g-C3N4, GCN)/sodium niobate (NaNbO3) heterojunction was investigated under ultrasonication. Herein, optimized GCN(50)/NaNbO3 heterojunction achieved 87.2% MET removal within 160 min (k = 0.0138 min-1). A new pathway for the generation of reactive oxygen species (ROS) via GCN(50)/NaNbO3 piezocatalytic heterojunction was identified. The type-II heterojunction formulated using optimized GCN(50)/NaNbO3 was found to generate hydroxyl radical (.OH); however, it was thermodynamically not feasible. The main reasons are; (i) piezopotential generated converted type-II to S-scheme heterojunction and resulted in the participation of high oxidizing potential holes in valence band (VB) of NaNbO3, and (ii) formation of depletion region at the GCN-water interface and subsequent improvement in the redox potential of holes, and (iii) piezopotential generated at NaNbO3 provided bias to GCN and established a piezo-electrocatalytic system. The higher screening of piezopotential in presence of external ions was found to reduce the generation of .OH. Overall, self-powered NaNbO3 has great ability to improve interfacial charge transfer at GCN(50)/NaNbO3 to form ROS.


Interaction of plasma gelsolin with tropomyosin.
Horse plasma gelsolin labelled with benzophenone-4-isothiocyanate can be photochemically cross-linked to rabbit cardiac tropomyosin. The cross-linking proceeds with greater efficiency in calcium-containing buffers. Further evidence for interaction between these proteins is provided by retention of fluorescently labelled gelsolin on tropomyosin-agarose affinity columns and by the ability of tropomyosin to cause an increase in the fluorescence intensity of gelsolin labelled with fluorescein-5-isothiocyanate. Both of these effects require the presence of calcium ions.


Novel vaccination protocol consisting of injecting MUC1 DNA and nonprimed dendritic cells at the same region greatly enhanced MUC1-specific antitumor immunity in a murine model.
In order to induce specific antitumor immunity in mice, we attempted to immunize C57BL/6 mice with DNA vaccine encoding MUC1 polypeptide. When the mice immunized with MUC1 DNA were challenged with EL4-muc, MUC1-transfected syngeneic lymphoma cells, they completely rejected tumors. When DNA vaccine was given to the EL4-muc tumor-bearing mice, this vaccination was insufficient to suppress tumor growth in the mice. However, activated, but nonprimed dendritic cells (DCs) obtained from syngeneic mice and MUC1 DNA vaccine were given simultaneously to the same site of EL4-muc tumor-bearing mice, tumor growth was markedly suppressed accompanying prolongation of survival time. MUC1 antigen was detected on the DCs at the vaccination site and in regional nodes in the mice which received MUC1 DNA vaccine and DCs. These mice showed markedly enhanced cellular immune responses specific for MUC1 compared to those in mice vaccinated with MUC1 DNA alone. No significant difference in titers of antibodies to MUC1 between the two groups was observed. These results suggest that nonprimed DCs inoculated at the DNA vaccine site are essential for eliciting strong antitumor cellular immunity to suppress tumor growth efficiently in DNA-vaccinated mice. This animal model is useful for developing DNA vaccine for anti-cancer immunotherapy.


The metatarsal osteotomy: a 10-year follow-up on the second, third and fourth metatarsal osteotomies and a new approach to the fifth metatarsal osteotomy.
The metatarsal osteotomy, a relatively simple procedure, provides a great amount of correction and relief with a limited amount of bone resection. Postoperative pain and edema are minimal, and disability and loss of time from employment are eliminated as patients are able to walk immediately in a surgical shoe. If biomechanical management is not adequate in relieving discomfort, then a 10-year study of more than 1000 cases indicates that the osteotomy is the procedure of choice.


Myeloproliferative disorder by TKO.
In this issue of Cell Stem Cell, Viatour et al. (2008) delete all three members of the retinoblastoma tumor suppressor gene family in hematopoietic stem cells, resulting in a myeloproliferative disorder. The disease was cell autonomous and resulted from alterations in the primitive hematopoietic cells.


[Cerebral metastasis of a "ghost" bronchopulmonary tumor].
Carcinoma of unknown primary (CUP) is the metastasis of epithelial malignancy whose origin remains unknown. Bronchial carcinoma is the most common cause (45%), however, in more than a quarter of cases, its origin is unknown and the choice of therapy often justifies a histopathological precision brought by the immuno-histochemistry. We present a rare case of cerebral metastasis, revealing an unknown lung cancer after a comprehensive review. This is a patient aged 53 years, chronic smoker, who presented a year and a half ago a sudden loss of consciousness with afebrile tonic-clonic seizure of spontaneous resolution. Clinical examination was unremarkable. Brain imaging by MRI has objectified the presence of two parietal tissue formations, which stereotactic biopsy with histological and immuno-histochemical favored metastasis of lung adenocarcinoma origin. An etiologic in search of the primitive lung remained negative (chest X-ray of face, chest CT and bronchoscopy with sampling upper gastrointestinal endoscopy). The rest of the etiologic, looking for another primitive, remained negative. The diagnosis of a bronchogenic carcinoma with brain metastasis is therefore withheld. The patient received two brain radiotherapies (gamma kniff) with regression of the two nodular formations. We have not given specific treatment and have called for very close monitoring of the patient who remained stable after 18 months. Through this observation, we stress the interest of the histology and immuno-histochemistry of carcinoma of unknown primary (CUP) to the diagnosis, guide therapy and determine prognosis.


Assesment of Prelacrimal Recess in Patients With Maxillary Sinus Hypoplasia Using Cone Beam Computed Tomography.
The prelacrimal recess approach, is frequently preferred in creating a minimally invasive surgical corridors. The aim of this study was to evaluate the Prelacrimal recess (PLR) anatomy using Cone Beam Computed Tomography in patients with Maxillary Sinus Hypoplasia. The paranasal Cone Beam Computed Tomography series of 84 adults were analyzed retrospectively. The antero-posterior and mesio-distal widths of the PLR and the antero-posterior width of the naso-lacrimal duct were measured. The patients were divided into three groups according to the antero-posterior width of PLR to evaluate the feasibility of prelacrimal recess approach as Type 1 (0-3 mm), Type 2 (>3-7 mm) and Type 3 (>7 mm). The mean antero-posterior width of PLR was 3.11 ± 1.49mm in the patients and 4.77 ± 1.76 mm in the controls. The mean mesio-distal width of PLR was 7.64 ± 1.49 mm in the patients and 3.17 ± 2.05 mm in the controls. The mean antero-posterior width of naso-lacrimal duct was 9.58 ± 2.80 mm in the patients and 9.46 ± 2.42 mm in the controls. The width of the antero-posterior PLR in patients with Maxillary Sinus Hypoplasia was found to be significantly lower in comparison to individuals with normal maxillary sinuses in the measurements performed on paranasal Cone Beam Computed Tomography scans. Hence, while planning a Functional Endoscopic Sinus Surgery with prelacrimal recess approach for maxillary sinus, the anatomical structure of the naso-sinusoidal region should be carefully analyzed, and individual anatomical variations such as Maxillary Sinus Hypoplasia should not be ignored.


From herbicide to flame retardant: The lamellar-like phosphorus-bridged amitrole toward high fire safety epoxy resin with light smoke and low toxicity.
In an attempt to alleviate the harmful impact of the flammability of epoxy resin on the environment, amitrole, a herbicide, has been converted to a novel flame retardant (PBA) with lamellar morphology through organophosphorus modification. This material has been utilized to fabricate fire safe epoxy thermosets (EP). EP containing 7.5 wt% PBA undergoes quick self-extinguishment upon ignition. This blend displays a high limiting oxygen index (LOI) value of 34%. More importantly, hazardous products (heat, smoke, toxic gases including CO/CO2) released during combustion of EP, are strongly suppressed in the presence of PBA. The mechanical properties of EP-PBA blends are comparable to those of virgin EP. The tensile strength of EP containing PBA is 90% of that of unmodified EP. The flexural strength of PBA blends is somewhat greater than that for EP containing no additive. A tactful strategy for the transformation of amitrole, a potential environmental contaminant to a benign flame retardant for polymers has been developed.


Development of immune responsiveness to Ascaris suum antigens in pigs vaccinated with ultraviolet-attenuated eggs.
Pigs fed Ascaris suum eggs attenuated by short wave ultraviolet-radiation developed resistance to challenge infection. Per os inoculation of pigs on three successive weeks with 10,000 eggs irradiated to total exposures of 150,100 and 75 microW-min/cm2, respectively, resulted in an 88% reduction in the number of larvae recovered from the lungs 7 days after challenge with 10,000 infective eggs. Peripheral blood lymphocytes (PBL) from vaccinated pigs were specifically stimulated in vitro to incorporate tritiated thymidine by egg hatching fluid (Ea) and by excretory-secretory products obtained from cultures and from cultures of third-stage larvae developing to fourth-stage (L3-4). PBL were also specifically stimulated by living L2. Ea and L2 stimulated pig PBL significantly at 7 days after the first inoculation; responses to L2-3 and L3-4 developed 7 days after a second inoculation. The antigen-responsive cells in the PBL population were non-immunoglobulin-bearing lymphocytes. Antibodies to Ea and L2-3 were not detected in the serum of vaccinated pigs, and only 3 of 7 pigs had low concentrations of serum antibodies to L3-4.


Detection of hazardous chemical using dual-wavelength Raman spectroscopy in the ultraviolet region.
This study proposes a stand-off Raman spectroscopy system using dual-wavelength in the ultraviolet (UV) region to detect hazardous chemicals. The Raman spectrum generated by the UV excitation source avoids solar background noise during daytime for chemical detection as the spectrum is in the solar blind range. Wavelengths of 213 and 266 nm by 5th and 4th harmonics are generated from Nd:YAG laser. However, Raman spectra of chemicals exhibit different signal-to-noise ratios for both the excitation wavelengths; therefore, to detect such chemicals, Raman spectra by two sources are required. Raman spectra were acquired using a dual-wavelength laser and spectrometer with a single grating and detector at the wavelengths of 213 and 266 nm simultaneously. The Raman spectra of sulfuric acid, 2-chloroethyl ethyl sulfide, and dimethyl methylphosphonate were acquired and analyzed, thus highlighting the application of dual-wavelength Raman spectroscopy. For efficient chemical detection in the field, we have ensured that the system developed in this study is robust.


[The influence of inhomogenity on strength of bones (author's transl)].
The authors experiments (n = 50) and calculation (n = 1000) with human hollow bone revealed physical and chemical data which were compared. It was shown that the physical and chemical properties are different in the diaphysis and epiphysis. These regularities are the consequence of the physical and chemical inhomogenities. These findings can be explained as a mechanism of protection.


Nonodontogenic Tumors of the Jaws.
Nonodontogenic tumors of the jaws are common in the pediatric population, accounting for approximately 70% of pediatric jaw tumors. This article focuses on the clinical characteristics and management of the benign nonodontogenic tumors (nonaggressive and aggressive) of the jaws most commonly encountered in children.


Comparative safety profiles of hirulog and heparin in patients undergoing coronary angioplasty. The Hirulog Angioplasty Study Investigators.
Several new anticoagulants and antiplatelet agents have been developed for use in coronary angioplasty, but almost all have been associated with an increased incidence of bleeding complications. Hirulog, a direct thrombin inhibitor, has several theoretical advantages over heparin. It is unclear, however, whether the use of hirulog as a substitute for heparin in angioplasty would result in a higher incidence of bleeding or other side effects. The safety profile of hirulog was compared with that of heparin in a randomized, double-blind trial in 4312 patients who were scheduled to undergo angioplasty for unstable or postinfarction angina. The goal of anticoagulation was to achieve an activated clotting time of approximately 350 seconds with hirulog (bolus dose of 1.0 mg/kg body weight followed by a 4-hour infusion of 2.5 mg/kg per hour and a 14- to 20-hour infusion of 0.2 mg/kg per hour) or heparin (bolus dose of 175 units/kg followed by an 18- to 24-hour infusion of 15 units/kg per hour). Adverse events were recorded prospectively by study personnel and confirmed independently by clinical monitors blinded to treatment assignment. Compared with heparin in an intention-to-treat analysis, hirulog therapy was associated with either equivalent or lower rates of side effects. Most of the side effects of hirulog and heparin were related to hemorrhagic complications such as intravascular puncture site hemorrhage (29.1% vs 61.6%; p < 0.001), hematuria (16.6% vs 20.6%; p = 0.001), bleeding requiring red cell transfusion (3.7% vs 8.6%; p < 0.001), or hematemesis (0.8% vs 1.9%; p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


The epidemiology and resuscitation effects of cardiopulmonary arrest among hospitalized children and adolescents in Beijing: an observational study.
To investigate the epidemiology and resuscitation effects of cardiopulmonary arrest among hospitalized children and adolescents in Beijing. A prospective multicentre study was conducted in four hospitals in urban/suburban areas of Beijing. Patients aged 1 month-18 years with cardiopulmonary arrest and received cardiopulmonary resuscitation (CPR) who were consecutively hospitalised during the study period (1 September 2008-31 December 2010) were enrolled. Data was collected and analyzed using the "in-hospital Utstein style". Neurological outcome was assessed with the pediatric cerebral performance category (PCPC) among patients who survived. 201 of 108,673 hospitalized patients (0.18%) had cardiopulmonary arrest during their hospitalization. Of these, 174 patients underwent CPR. The most common causes of cardiopulmonary arrest were the diseases of respiratory system (29.3%) and circulatory system (19.0%). The most common initial rhythm was bradycardia (72.4%). About 108 patients (62.1%) had restoration of spontaneous circulation (ROSC). Forty-nine patients (28.2%) survived to hospital discharge, 25 (14.5%) survived 6 months post discharge, and 21 (12.1%) survived 1 year post discharge. Out of the 21 patients who survived 1 year after hospital discharge, 18 had good neurological outcome. Multivariate logistic regression analysis showed age, duration of CPR and endotracheal intubation performed before cardiopulmonary arrest were independent factors of cardiopulmonary resuscitation effect. The prevalence of in-hospital cardiopulmonary arrest in children and adolescents is low. The long-term result of children and adolescents survived from cardiopulmonary resuscitation is quite good. Age, CPR duration and endotracheal intubation performed before cardiopulmonary arrest were independent factors of cardiopulmonary resuscitation effect.


Recent advances in the study of sepsis-induced depression.
Progress in medicine such as the use of anti-infective drugs and development of the advanced life support equipment has greatly improved the survival rate of patients with sepsis. However, the incidence of sepsis-related diseases is increasing. These include severe neurologic and psychologic disorders, cognitive decline, anxiety, depression, and post-traumatic stress disorder. Cerebral dysfunction occurs via multiple interacting mechanisms, with different causative pathogens having distinct effects. Because sepsis-related diseases place a substantial burden on patients and their families, it is important to elucidate the underlying pathophysiologic mechanisms to develop effective treatments.


World Association for the Advancement of Veterinary Parasitology (WAAVP): Second edition of guidelines for evaluating the efficacy of anthelmintics for dogs and cats.
These revised guidelines have been developed to assist in the design, execution, and interpretation of studies to assess the efficacy of anthelmintic drugs against internal parasites in dogs and cats. The design and execution of studies are outlined and discussed. Considerations for specific targeted parasites are included. Information is provided on the principles of selection of animals, procedures for randomization, housing, feeding, necropsy procedures, and record keeping for dose determination dose confirmation studies and field studies. Complementary to the WAAVP general anthelmintic guidelines, these species-specific guidelines should assist investigators in the evaluation of anthelmintic drugs in dogs and cats by using comparable and standardized procedures in studies with appropriate numbers of animals.


Impact of residual inflammation on myocardial recovery and cardiovascular outcome in Takotsubo patients.
Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo syndrome (TTS). In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. Three hundred eighty-five patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP <5.2 mg/L, CRP range 5.2 to 19 mg/L, and CRP >19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP >19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Follow up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow up (61.7% vs. 60.7% vs. 57.9%; P = 0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; P = 0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.87; 95% confidence interval: 1.08 to 3.25; P = 0.025). Residual high inflammatory response was associated with impaired LVEF at follow up and was evidenced as an independent factor of cardiovascular events. All together, these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR.


Mixed conductive and sensorineural hearing loss in LP/J mice.
Air and bone conduction thresholds for the detection of a compound action potential response were measured in mice of the LP/J inbred strain, which has been proposed as a possible model for human otosclerosis. Thresholds were compared with control data from CBA/Ca mice. Evidence of a mixed sensorineural and conductive hearing loss was obtained in LP/J mice. Few signs of hair cell degeneration or middle-ear bony lesions were found in 20-day old mice, although they generally showed raised thresholds to both air and bone conducted stimuli. The reason for the observed sensorineural component of the hearing loss at this age is not clear, since endocochlear potentials were normal in mice of this strain. By 225 days of age, hair cell loss was extensive and there was clearly excess bone growth in all middle-ear specimens studied, particularly on the incus and the cochlear wall facing the middle ear. Microbiological analysis of LP/J specimens revealed no evidence of a middle-ear infection specific to these mice which might explain the pathology.


Acceptability of Long Versus Short Firearm Safety Education Videos in the Emergency Department: A Pilot Randomized Controlled Trial.
Safe firearm storage is protective against pediatric firearm injuries. We sought to compare a 3-minute versus 30-second safe firearm storage video in terms of acceptability of video content and use in the pediatric emergency department (PED). We conducted a randomized controlled trial in a large PED (from March to September 2021). Participants were English-speaking caregivers of noncritically ill patients. Participants were surveyed about child safety behaviors (including firearm storage), then shown 1 of 2 videos. Both videos described safe storage principles; the 3-minute video included temporary firearm removal and a survivor testimonial. The primary outcome was acceptability, measured by responses on a 5-point Likert scale (strongly disagree to strongly agree). A survey at 3 months evaluated information recall. Baseline characteristics and outcomes were compared between groups using Pearson chi-squared, Fisher exact, and Wilcoxon Mann Whitney tests as appropriate. Absolute risk difference for categoric variables and mean difference for continuous variables are reported with 95% confidence interval (CI). Research staff screened 728 caregivers; 705 were eligible and 254 consented to participate (36%); 4 withdrew. Of 250 participants, most indicated acceptability in terms of setting (77.4%) and content (86.6%), and doctors discussing firearm storage (78.6%), with no difference between groups. More caregivers viewing the longer video felt the length appropriate (99.2%) compared with the shorter video (81.1%, difference 18.1%, 95% CI 11.1 to 25.1). We show that video-based firearm safety education is acceptable among study participants. This can provide consistent education to caregivers in PEDs and needs further study in other settings.


Role of serum FSH measurement on bone resorption in postmenopausal women.
In vitro and animals models have shown follicle-stimulating hormone (FSH) effects on osteoclastic function, and FSH levels seem to influence bone loss independently of estrogen concentrations in humans. Our aim was to evaluate the role of serum FSH measurement in the assessment of bone resorption in postmenopausal women. We conducted a cross-sectional study including 92 postmenopausal healthy women aged 56.2 (3.6) and 7.2 (4) years since menopause. Serum FSH, luteinizing hormone (LH), estradiol (E2) and bone turnover markers as osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) were measured. We analyzed the relationship between serum levels of gonadotropins, E2, and bone turnover markers. Serum levels of OC and CTX were positively related to FSH (r = 0.234, P = 0.047 and r = 0.384, P = 0.003) and LH (r = 0.319, P = 0.012 and r = 0.273, P = 0.038). There was no relationship with E2 levels. When gonadotropins levels were divided into quartiles, we found significant differences in bone turnover markers between the first and the fourth quartile. OC levels were higher in the highest quartile of FSH (P = 0.024) and LH (P = 0.001). Serum CTX was also higher in the highest quartile of FSH (P = 0.004) and LH (P = 0.039). FSH levels could explain approximately 14.7% of the chances in CTX. In summary, gonadotropins were related to bone turnover in postmenopausal healthy women. Moreover, the rise in FSH appears to contribute to higher bone resorption. Our results suggest that the measurement of FSH could be usefulness to perform a more comprehensive assessment of bone loss in these women.


Adenosine deaminase in body fluids: a useful diagnostic tool in tuberculosis.
The performance of a colorimetric ADA determination in body fluids other than serum in the diagnosis of tuberculosis was assessed in 1063 patients from whom pleural (600), peritoneal (136), pericardial (77), or cerebrospinal (250) fluids were obtained. In exudative pleuroperitoneal and pericardial effusions, an ADA decision level of 0.71 mu kat/L displayed a sensitivity of 1.00, and was higher than those of histologic (0.83) and bacteriologic (0.62) studies. At this level, ADA reached a specificity of 0.92 and efficiency of 0.94. In cerebrospinal fluid, an ADA catalytic concentration above 0.15 mu kat/L strongly suggests tuberculous meningitis in patients older than 7 years (sensitivity 1.00, specificity 0.99 and efficiency 0.99). ADA results obtained with a UV-method were closely correlated with those of the colorimetric method in pleuroperitoneal effusions (r = 0.989) and in cerebrospinal fluids (r = 0.905). Sample blanks should be processed, otherwise false positive results may be found in non-tuberculous cerebrospinal fluids (5.3%) and pleuroperitoneal effusions (3.8%).


Increase in vulnerability of atrial fibrillation in an acute intermittent hypoxia model: importance of autonomic imbalance.
The underlying mechanism of atrial fibrillation (AF) in association with hypoxia remains unclear. This study aimed to investigate the AF vulnerability in an acute intermittent hypoxia model and ascertained the mechanism. In 15 anesthetized open-chest dogs (10 experimental and 5 control), multiple-electrode catheters were sutured to the surface of atria, pulmonary veins and superior vena cava. The ventilators were adjusted to simulate the intermittent hypoxia for 1h. The heart rate, blood pressure, blood gas, heart rate variability (HRV), effective refractory period (ERP) and window of vulnerability (WOV) as a measure of AF inducibility were measured. As the hypoxia prolonged, the pH, PaO2 and SaO2 progressively decreased, while the PaCO2 increased (P<0.05 for all). In the first 30 min of hypoxia, the HRV indexes associated with sympathetic activity (LF) and parasympathetic activity (HF) both increased but the ratio of LF/HF stayed unchanged. The ERP and WOV were not affected. In the second 30 min of hypoxia, the parasympathetic activity (HF) further increased while the ratio of LF/HF subsequently decreased. Meanwhile, the ERP shortened, and the WOV significantly increased (P<0.05 for all). All the changes that were caused by hypoxia were reversed by 1-h re-ventilation. AF vulnerability increases in the acute intermittent hypoxia model in which autonomic imbalance may play an important role. The treatment targeting autonomic imbalance may be considered when encountering this kind of AF such as in sleep apnea.


Simulated single-cycle kinetics improves the design of surface plasmon resonance assays.
Instruments based on the surface plasmon resonance (SPR) principle are widely used to monitor in real time molecular interactions between a partner, immobilized on a sensor chip surface and another one injected in a continuous flow of buffer. In a classical SPR experiment, several cycles of binding and regeneration of the surface are performed in order to determine the rate and the equilibrium constants of the reaction. In 2006, Karlsson and co-workers introduced a new method named single-cycle kinetics (SCK) to perform SPR assays. The method consists in injecting sequentially increasing concentrations of the partner in solution, with only one regeneration step performed at the end of the complete binding cycle. A 10 base-pair DNA duplex was characterized kinetically to show how simulated sensorgrams generated by the BiaEvaluation software provided by Biacore™ could really improve the design of SPR assays performed with the SCK method. The DNA duplex was investigated at three temperatures, 10, 20 and 30 °C, to analyze fast and slow rate constants. The results show that after a short obligatory preliminary experiment, simulations provide users with the best experimental conditions to be used, in particular, the maximum concentration used to reach saturation, the dilution factor for the serial dilutions of the sample injected and the duration of the dissociation and association phases. The use of simulated single-cycle kinetics saves time and reduces sample consumption. Simulations can also be used to design SPR experiments with ternary complexes.


Diagnostic tests, treatment and follow-up in heart failure patients--is there a gender bias in the coherence to guidelines?
To relate clinical data in a consecutive cohort of patients admitted with heart failure in Sweden to demographic data and the use of diagnostic tests, medical treatment, care process and mortality. Retrospective investigation of all charts concerning patients discharged with primary diagnosis of heart failure in two Swedish hospitals during the second half of 1995 was undertaken. Records from 187 men and 192 women were analyzed, median age was 78 years. During hospital stay 75% of the patients, regardless of gender, were examined with chest radiography. Echocardiography was performed in 59% of all patients, more often in men than in women (68% vs. 55%, P<0.011). The proportion of patients receiving ACE-inhibitors was higher if echocardiography had been performed, in both men (38% vs. 72%, P<0.001) and women (38% vs. 55%, P<0.033). Mean hospital stay was 6.4 days. After discharge 57% of the patients were referred to the general practitioners (GP), 21% to the hospital outpatient clinic. Young age (P<0.001), male gender (P<0.01) and treatment with beta-blocking agents (P<0.035) were independently related to referral to hospital outpatient clinic. Within the group referred to the GPs, 62% of the patients had a follow-up visit within 3 months after discharge while 49% had visited the hospital outpatient clinic. The 1-year mortality rate was high, 30%. Patients admitted with heart failure in Sweden are old and carry a poor prognosis. In spite of the poor prognosis, only approximately half of the patients are followed-up within 3 months after discharge. There is, in contrast to practice guidelines, an underuse of diagnostic tests of left ventricular function and medical treatment is often suboptimal. These unsatisfactory findings were more pronounced in women.


Pain response of neonates to venipuncture.
To study the physiological and behavioral response to pain. 80 healthy neonates requiring bilirubin estimation, blood sugar etc, were randomly assigned to receive a venous puncture. All parameters were recorded 10 minutes prior, during and 10 minutes after the procedure. Evaluated NIPS score and RR. HR, NIBP and O2 saturation observed on Datex-Ohmeda multimonitor. After the venepuncture, heart rate (p<0.001) and blood pressure (p<0.001) were significantly increased in both the groups but more significant increase was present in Group I (>2.5 kg) as compared to Group II (>2.5 kg). Respiratory rate was also increased but more significant in Group II (p<0.001) whereas oxygen saturation was decreased in both the groups but more significant in Group I (p<0.001). Median Neonatal Infant Pain Scale (NIPS) score was higher in both the Groups (p<0.001). The outcome measures appear to be reliable indices of term neonates responses to painful stimulation. NIPS are suitable instruments for neonatal pain evaluation.


Tranexamic versus aminocaproic acids in patients with total hip arthroplasty: a retrospective study.
Recently, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) have been applied in total hip arthroplasty (THA). However, doubts in clinicians' minds about which medicine is more efficient and economical in THA need to be clarified. Therefore, this study compared the efficacy and cost of the intraoperative administration of TXA and EACA per surgery in decreasing perioperative blood transfusion rates in THA. This study enrolled patients who underwent THA between January 2019 to December 2020. A total of 295 patients were retrospectively divided to receive topical combined with intravenous TXA (n = 94), EACA (n = 97) or control (n = 104). The primary endpoints included transfusions, estimated perioperative blood loss, cost per patient and the drop in the haemoglobin and haematocrit levels. Patients who received EACA had greater total blood loss, blood transfusion rates, changes in HGB levels and mean cost of blood transfusion per patient (P < 0.05) compared with patients who received TXA. In addition, both TXA and EACA groups had significantly fewer perioperative blood loss, blood transfusion, operation time and changes in haemoglobin and haematocrit levels than the control group (P < 0.05). Cost savings in the TXA and EACA groups were 736.00 RMB and 408.00 RMB per patient, respectively. The application of perioperative antifibrinolytics notably reduces the need for perioperative blood transfusions. What's more, this study demonstrated that TXA is superior to EACA for decreasing blood loss and transfusion rates while at a lower cost per surgery. These results indicate that TXA may be the optimum antifibrinolytics for THA in Chinese area rather than EACA.


The impact of the "grim reaper" national AIDS educational campaign on the Albion Street (AIDS) Centre and the AIDS Hotline.
The national educational programme on the acquired immunodeficiency syndrome (AIDS) caused a dramatic increase in the number of heterosexual persons who presented for human immunodeficiency virus (HIV) antibody testing at the Albion Street (AIDS) Centre. There was also a marked increase in the number of intravenous drugs abusers who presented, although the proportion of this high-risk group that has been tested remains low. There was no increase in the number of homosexual men who presented for testing. The increase in the number of telephone calls that were received by the Centre's AIDS Hotline was due to an interest in HIV-antibody testing, rather than an interest in information about safer sexual practices. The campaign was seen to have achieved its primary objective, namely, to alert sexually-active persons of the potential spread of the virus from the high-risk groups. However, it is clear that future educational campaigns need to target specific high-risk groups such as intravenous drug abusers.


Synergistic effect of ultrasonication and sulfate radical on recovering cobalt and lithium from the spent lithium-ion battery.
Ultrasonication has been mechanically applied widely in the recycling of spent lithium-ion (SLI) batteries while its influence on chemical pathways has barely been reported. In this study, ultrasonication and sulfate radicals were used in a coupling system to obtain efficient recoveries of Co and Li from SLI batteries. The synergistic effect of ultrasonication and sulfate radicals on recycling was quantitatively analysed by significance analysis and surface responses in a central composite design. The employment of persulfate significantly affected the whole recycling process during the sonication. Factors including acoustic time, operating powers, and temperature all had a significant effect on the recoveries of Co and Li. The maximum recovery efficiencies of Co and Li of 97.33% and 99.25%, respectively, and the minimum loss rate of Al of 4.13% were simultaneously obtained by the fitting predictor. The optimal combination of factors for the sonication system included an acoustic time (min) of 5.5, an operating power (W) of 168, a temperature (°C) of 86, and a ratio of cathode foil to S-solution (mg/mL) of 1:60. A moiety of cathode active material was directly separated from the aluminium collector by sulfate radical-related reactions. Co and Li cations dissolved from LiCoO2 by carbon dioxide radicals were reprecipitated by excess oxalate. The research demonstrated the positively synergistic influence caused by ultrasonication and sulfate radicals on achieving efficient recoveries of Co and Li from SLI batteries, explicitly expanding the technical choices for the recycling procedure.


METTL3 inhibition ameliorates liver damage in mouse with hepatitis B virus-associated acute-on-chronic liver failure by regulating miR-146a-5p maturation.
Hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) is a clinical syndrome of severe liver damage. HBV infection is affected by N6-methyladenosine (m6A) RNA modification. Here, we investigated whether methyltransferase-like 3 (METTL3)-mediated m6A methylation can affect ACLF. Human hepatic cells (THLE-2) were treated with lipopolysaccharide (LPS) to induce cell damage. Proliferation, apoptosis and m6A modification were measured by MTT assay, flow cytometry and Dot blot assay. Our results showed that HBV infection significantly enhanced the levels of m6A modification and elevated the expression of METTL3 and mature-miR-146a-5p in THLE-2 cells, which was repressed by cycloleucine (m6A inhibitor). METTL3 overexpression enhanced m6A modification and promoted mature-miR-146a-5p expression. METTL3 overexpression promoted HBV replication and apoptosis, enhanced the levels of pro-inflammatory cytokines, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), and repressed cell proliferation in THLE-2 cells, which attributed to repress miR-146a-5p maturation. Moreover, a severe liver failure mouse model was established by HBV infection to verify the impact of METTL3 knockdown on liver damage in vivo. HBV-infection led to a severe liver damage and increase of apoptosis in hepatic tissues of mice, which was abolished by METTL3 knockdown. METTL3 knockdown reduced METTL3 expression and impeded miR-146a-5p maturation in HBV-infected mice. In conclusion, this work demonstrates that METTL3 inhibition ameliorates liver damage in mouse with HBV-associated ACLF, which contributes to repress miR-146a-5p maturation. Thus, this article suggests a novel therapeutic avenue to prevent and treat HBV-associated ACLF.


Topological engineering of terahertz light using electrically tunable exceptional point singularities.
The topological structure associated with the branch point singularity around an exceptional point (EP) can provide tools for controlling the propagation of light. Through use of graphene-based devices, we demonstrate the emergence of EPs in an electrically controlled interaction between light and a collection of organic molecules in the terahertz regime at room temperature. We show that the intensity and phase of terahertz pulses can be controlled by a gate voltage, which drives the device across the EP. Our electrically tunable system allows reconstruction of the Riemann surface associated with the complex energy landscape and provides topological control of light by tuning the loss imbalance and frequency detuning of interacting modes. Our approach provides a platform for developing topological optoelectronics and studying the manifestations of EP physics in light-matter interactions.


Identification and Analysis of OVATE Family Members from Genome of the Early Land Plants Provide Insights into Evolutionary History of OFP Family and Function.
Mosses, liverworts, hornworts and lycophytes represent transition stages between the aquatic to terrestrial/land plants. Several morphological and adaptive novelties driven by genomic components including emergence and expansion of new or existing gene families have played a critical role during and after the transition, and contributed towards successful colonization of terrestrial ecosystems. It is crucial to decipher the evolutionary transitions and natural selection on the gene structure and function to understand the emergence of phenotypic and adaptive diversity. Plants at the "transition zone", between aquatic and terrestrial ecosystem, are also the most vulnerable because of climate change and may contain clues for successful mitigation of the challenges of climate change. Identification and comparative analyses of such genetic elements and gene families are few in mosses, liverworts, hornworts and lycophytes. Ovate family proteins (OFPs) are plant-specific transcriptional repressors and are acknowledged for their roles in important growth and developmental processes in land plants, and information about the functional aspects of OFPs in early land plants is fragmentary. As a first step towards addressing this gap, a comprehensive in silico analysis was carried out utilizing publicly available genome sequences of Marchantia polymorpha (Mp), Physcomitrella patens (Pp), Selaginella moellendorffii (Sm) and Sphagnum fallax (Sf). Our analysis led to the identification of 4 MpOFPs, 19 PpOFPs, 6 SmOFPs and 3 SfOFPs. Cross-genera analysis revealed a drastic change in the structure and physiochemical properties in OFPs suggesting functional diversification and genomic plasticity during the evolutionary course. Knowledge gained from this comparative analysis will form the framework towards deciphering and dissection of their developmental and adaptive role/s in early land plants and could provide insights into evolutionary strategies adapted by land plants.


Gait analysis in a mouse model resembling Leigh disease.
Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease.


Protection of guinea pigs against Leptospira interrogans serovar Lai by LipL21 DNA vaccine.
In this study, the full lipL21 gene fragment encoding outer membrane protein LipL21 was cloned from L. interrogans serovar Lai and inserted into eukaryotic expression vector pcDNA3.1(+). The guinea pigs were immunized with pcDNA3.1(+)-lipL21, pcDNA3.1(+) or PBS. Six weeks after the second immunization, the splenocytes were isolated to detect their proliferative ability by lymphocyte transformation experiments. In addition, microscopic agglutination test was used for quantitative detection of specific antibodies. The rest guinea pigs were challenged intraperitoneally with L. interogans sorevar Lai. Then, protective effect was evaluated on the basis of survival and histopathological lesions in the kidneys, lungs, and liver. The lipL21 gene was successfully expressed in COS-7 cells through recombinant pcDNA3.1(+)-lipL21. The titer of specific antibodies substantially increased, and the stimulation index of splenocytes increased significantly. Hence, the pcDNA3.1(+)-lipL21 could protect the immunized guinea pigs from homotypic Leptospira infection. Furthermore, no obvious pathologic changes were observed in the pcDNA3.1(+)-lipL21 immunized guinea pigs. The results showed that the protective effect with pathogenic strains of Leptospira was shared by LipL21 mediated through a plasmid vector. Consequently, these results indicated that the lipL21 DNA vaccine was a promising candidate for the prevention of leptospirosis.


Effect of rehydration on textural properties, oral behavior, kinetics and water state of textured wheat gluten.
To reduce the rehydration time and improve the quality of textured wheat gluten (TWG), the effects of steam pretreatment and water temperature (45 °C, 65 °C, and 85 °C) on the rehydration of TWG were investigated. Four different models were used to describe the rehydration kinetics: Peleg, Weibull, first-order, and exponential association models, with the Weibull model found to give the best fit. High temperature induced deterioration of textural properties and oral processing behavior and increased the rehydration loss ratio, while steam pretreatment reduced these negative changes. Morphological results showed that the surface and cross-sectional structure were conducive to water diffusion with steam pretreatment. Low-field nuclear magnetic resonance and infrared thermal results indicated that steam pretreatment promoted the diffusion of water and reduced the time required to reach thermal equilibrium. This work provides a fast rehydration method for TWG to help in the future production of high-quality meat analogues.


Ankle lateral ligament reconstruction for chronic instability.
To report the outcome of a technique combining direct anatomic reconstruction of the anterior talofibular ligament (ATFL) with augmented reconstruction using the peroneus brevis tendon fixed by a bio-absorbable interference screw. 13 men and 2 women aged 17 to 36 (mean, 24) years with recurrent inversion injuries of the right (n=5) and left (n=10) ankles underwent lateral ankle reconstruction by a single surgeon. All patients had a positive anterior drawer test and heel eversion stress test, and some degree of tenderness to palpation over the anterolateral joint capsule. All patients had complete or partial tear of the ATFL and the calcaneofibular ligament, except for one. The torn ligaments were repaired anatomically and reinforced with a split peroneus brevis tendon rerouted through the fibula and fixed with a bioabsorbable interference screw. The outcome was assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and the Foot and Ankle Outcome Score (FAOS) at 6 months. The mean time from injury to surgery was 40.5 months. The mean follow-up duration was 13.6 (range, 6-26) months. No patient had surgical or wound complications. The mean AOFAS ankle and hindfoot score was 91.5 (median, 93; range, 79-100). The mean FAOS was 78.8 (median, 77; range, 61-100). 10 patients had no limitation in both daily and recreational activities; 3 had limitation in recreational activities, and 2 had limitation in both. 12 patients had normal and 3 had moderate limitation in hindfoot motion. One patient had hindfoot instability. The combination of augmented and direct anatomic reconstructions enables early mobilisation despite limitation in hindfoot motion and is a viable option for chronic hindfoot instability.


The paradox of left ventricular assist device unloading and myocardial recovery in end-stage dilated cardiomyopathy: implications for heart failure in the elderly.
Dilated cardiomyopathy (DCM) is a common debilitating condition with limited therapeutic options besides heart transplantation or palliation. It is characterized by maladaptive remodeling of cardiomyocytes, extracellular collagen matrix (ECCM) and left ventricular (LV) geometry which contributes to further dysfunction. LV assist devices (LVADs) can reverse adverse remodeling in end-stage DCM. However, there is a disconnect between the benefits of prolonged unloading with LVAD at molecular and cellular levels and the low rate of bridge to recovery (BTR). Potential explanations for this paradox include insufficient reverse ECCM remodeling and/or excessive reverse cardiomyocyte remodeling with atrophy. LVAD therapy is associated with decreased collagen turnover and cross-linking and increased tissue angiotensin II (AngII), whereas LVAD combined with angiotensin-converting enzyme inhibition results in decreased tissue AngII and collagen cross-linking, normalizes LV end-diastolic pressure volume relationships and is associated with modestly higher rates of BTR. Much remains to be learned about ventricular reverse remodeling after LVAD. This can be facilitated through systematic collection and comparison of recovered and unrecovered myocardium. Importantly, vigilant monitoring for ventricular recovery among LVAD patients is needed, particularly in older patients receiving LVAD for destination therapy. In addition, prospective multicenter trials are needed to clarify the potential benefit of concomitant heart failure therapy with selective β2 agonism on ventricular recovery.


Massive parallel sequencing in individuals with multiple primary tumours reveals the benefit of re-analysis.
Multiple primary cancers, defined as three or more primary tumours, are rare, and there are few genetic studies concerning them. There is a need for increased knowledge on the heritability of multiple primary cancers and genotype-phenotype correlations. We have performed whole-genome/exome sequencing (WGS/WES) in ten individuals with three or more primary tumours, with no previous findings on standard clinical genetic investigations. In one individual with a clinical diagnosis of MEN1, a likely pathogenic cryptic splice site variant was detected in the MEN1 gene. The variant (c.654C > A) is synonymous but we showed in a cDNA analysis that it affects splicing and leads to a frameshift, with the theoretical new amino acid sequence p.(Gly219Glufs*13). In one individual with metachronous colorectal cancers, ovarian cancer, endometrial cancer and chronic lymphocytic leukaemia, we found a likely pathogenic variant in the MLH1 gene (c.27G > A), and two risk factor variants in the genes CHEK2 and HOXB13. The MLH1 variant is synonymous but has previously been shown to be associated to constitutional low-grade hypermethylation of the MLH1 promoter, and segregates with disease in families with colorectal and endometrial cancer. No pathogenic single nucleotide or structural variants were detected in the remaining eight individuals in the study. The pathogenic variants found by WGS/WES were in genes already sequenced by Sanger sequencing and WES in the clinic, without any findings. We conclude that, in individuals with an unequivocal clinical diagnosis of a specific hereditary cancer syndrome, where standard clinical testing failed to detect a causative variant, re-analysis may lead to a diagnosis.


Antibiotic resistance patterns of bacterial bile cultures during pancreatic surgery-a single center analysis and systematic review.
Septic complications after pancreatic surgery are common. However, it remains unclear if and how a shift of the microbiological spectrum affects morbidity. The aim of the present study was to assess the microbiological spectrum and antibiotic resistance patterns and their impact on outcome. We conducted a retrospective study including patients undergoing pancreatic surgery at our center between 2005 and 2018. A systematic literature review and descriptive meta-analysis of the published and original data was performed according to the PRISMA guidelines. A total of 318 patients were included in the analysis. Patients with biliary drainage had a significantly higher incidence of bacterobilia (93% vs. 25%) and received preoperative antibiotics (46% vs. 12%). The analyzed bile cultures showed no resistance to piperacillin/tazobactam, fluoroquinolones, or carbapenems. Resistance to cefuroxime was seen in 58% of the samples of patients without biliary drainage (NBD) and 93% of the samples of those with drainage (BD). In general, there was no significant difference in overall postoperative morbidity. However, superficial surgical site infections (SSIs) were significantly more common in the BD group. We included a total of six studies and our own data (1627 patients) in the descriptive meta-analysis. The percentage of positive bile cultures ranged from 53 to 81%. In patients with BD, the most frequent microorganisms were Enterococcus spp. (58%), Klebsiella spp. (29%), and E. coli (27%). Almost all studies demonstrated resistance to first- and second-generation cephalosporins and to third- and fourth-generation cephalosporins for patients with BD. A change in perioperative antibiotic strategy according to local resistance patterns, especially after BD, might be useful for patients undergoing pancreatic surgery. Appropriate perioperative antibiotic coverage may help to prevent abdominal infectious complications and especially superficial SSIs.


Searching for Computational Strategies to Accurately Predict pKas of Large Phenolic Derivatives.
Twenty-two reaction schemes have been tested, within the cluster-continuum model including up to seven explicit water molecules. They have been used in conjunction with nine different methods, within the density functional theory and with second-order Møller-Plesset. The quality of the pKa predictions was found to be strongly dependent on the chosen scheme, while only moderately influenced by the method of calculation. We recommend the E1 reaction scheme [HA + OH(-) (3H2O) ↔ A(-) (H2O) + 3H2O], since it yields mean unsigned errors (MUE) lower than 1 unit of pKa for most of the tested functionals. The best pKa values obtained from this reaction scheme are those involving calculations with PBE0 (MUE = 0.77), TPSS (MUE = 0.82), BHandHLYP (MUE = 0.82), and B3LYP (MUE = 0.86) functionals. This scheme has the additional advantage, compared to the proton exchange method, which also gives very small values of MUE, of being experiment independent. It should be kept in mind, however, that these recommendations are valid within the cluster-continuum model, using the polarizable continuum model in conjunction with the united atom Hartree-Fock cavity and the strategy based on thermodynamic cycles. Changes in any of these aspects of the used methodology may lead to different outcomes.


Vibrational assignments and isomerization rate-constants from time-dependent F.t.-i.r. spectra of sugars.
Time-dependent F.t.-i.r. absorption spectra of alpha-D-galactose, alpha-D-fucose, alpha-D-glucose-1-d1, alpha-D-glucose-2-d1, and alpha-D-glucose-5,6,6-d3 were measured. The spectral changes were interpreted in terms of anomeric isomerization, and possible vibrational origins were suggested. The intensity changes seen for alpha-fucose were found to follow a reversible first-order rate-equation and the rate constants obtained from different vibrational bands were found to be consistent among themselves and in reasonable agreement with those obtained by other techniques.


Enrichment of extremely noisy high-throughput screening data using a naïve Bayes classifier.
The noise level of a high-throughput screening (HTS) experiment depends on various factors such as the quality and robustness of the assay itself and the quality of the robotic platform. Screening of compound mixtures is noisier than screening single compounds per well. A classification model based on naïve Bayes (NB) may be used to enrich such data. The authors studied the ability of the NB classifier to prioritize noisy primary HTS data of compound mixtures (5 compounds/well) in 4 campaigns in which the percentage of noise presumed to be inactive compounds ranged between 81% and 91%. The top 10% of the compounds suggested by the classifier captured between 26% and 45% of the active compounds. These results are reasonable and useful, considering the poor quality of the training set and the short computing time that is needed to build and deploy the classifier.


Bone marrow endothelial cells increase the invasiveness of human multiple myeloma cells through upregulation of MMP-9: evidence for a role of hepatocyte growth factor.
The migration of multiple myeloma (MM) cells from the circulation into the bone marrow (BM) implicates that they must have the capacity to cross the BM endothelium including the subendothelial basement membrane. In this study, human CD138+ MM cells were immunomagnetically isolated from BM samples of MM patients and their invasion through Matrigel, that is, a reconstituted basement membrane, was determined. We demonstrated that primary MM cells have the capacity to transmigrate through basement membrane and that this invasiveness was considerably increased when assessed on Matrigel filters coated with BM endothelial cells (EC) (4LHBMEC line) (transendothelial invasion). The isolated MM cells were shown by zymography to secrete matrix metalloproteinase (MMP)-9 and anti-MMP-9 antibodies inhibited transendothelial invasion, indicating that MMP-9 is involved in this process. BM EC were found to increase the MMP-9 secretion in MM cells, indicating that EC enhance MM cell invasion through stimulation of MMP-9 secretion. BM EC were found to produce hepatocyte growth factor (HGF), and this cytokine also stimulated MMP-9 secretion in MM cells, while anti-HGF antibodies significantly inhibited EC-stimulated MM cell invasion. In summary, our findings provide evidence that MM cell-BM EC interactions enhance the invasion of human MM cells through stimulation of MMP-9 secretion.


Prognostic Indicators for Survival and Athletic Outcome in Critically Ill Neonatal Foals.
Equine neonatal intensive care units have expanded knowledge and understanding of the normal and abnormal physiology of the equine neonate, resulting in successful treatment of critically ill equine neonates. The overall survival rate has increased tremendously since the early 1980s, from a little more than 50% to 80% or more for most facilities. The severely septic foal and the very premature foal still remain large treatment challenges, but less severely septic foals and foals challenged by adverse peripartum events such as dystocia and placentitis are surviving to hospital discharge and performing to the owners' expectation in larger numbers.


Tacrolimus therapeutic drug monitoring in Tunisian renal transplant recipients: effect of post-transplantation period.
Most previous studies having focused on therapeutic drug monitoring of tacrolimus in renal transplant recipients have assessed the clinical response of patients. The aim of this study is to investigate the influence of post-transplant delay on tacrolimus dose, trough levels (C0) and dose/C0 ratio in a Tunisian renal transplant population. A retrospective study including 110 renal transplant patients has been performed. Tacrolimus trough concentrations were adjusted according to the target range proposed by the European consensus conference on tacrolimus optimization. Samples for determination of tacrolimus blood level were subdivided according to the post-transplantation period into three groups. The initial dose required was 0.17 ± 0.05 mg/kg/day during the first 3 months after transplantation. A reduction of 36 and 65% of tacrolimus initial dose during the second (3-12 months) and third period after transplantation (>12 months), respectively, was required to maintain the concentration level within therapeutic range. These results were different from those found in other studies performed in different populations. We hypothesize that these differences in dosing requirement may be due to an interethnic polymorphism in the expression of enzymes involved in tacrolimus metabolism. These results could provide a simple therapeutic strategy to optimize tacrolimus prescription after renal transplantation in Tunisian population.


LncRNA MALAT1 inhibits apoptosis of endometrial stromal cells through miR-126-5p-CREB1 axis by activating PI3K-AKT pathway.
Endometriosis is a common, chronic and painful disease in women, whose pathogenesis remains not entirely clear. Long non-coding RNA (lncRNA) MALAT1 participates in the development of endometriosis. This study further investigated the regulation of MALAT1-miR-126-5p-CREB1 axis in the pathological process of endometriosis. MALAT1, miR-126-5p, and CREB1 levels in human endometrial stromal cells (HESCs) were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Protein levels were determined by Western blotting. Cell viability and apoptosis was assessed by MTT assay and annexin V-FITC staining, respectively. The interactivity between miR-126-5p and MALAT1 (or CREB1) was assessed by dual luciferase reporter system. Knockdown of MALAT1 or CREB1 restrained proliferation and induced apoptosis as confirmed by upregulating cleaved caspase-3 and Bax, and down-regulating Bcl-2 in HESCs, while inhibition of miR-126-5p presented the opposite results. Moreover, silencing of MALAT1 triggered apoptosis of HESCs via targeting miR-126-5p. In addition, miR-126-5p directly regulated CREB1 expression via binding to its 3' non-coding region. Finally, miR-126-5p inhibitor-mediated apoptosis inhibition was restrained by CREB1 silencing via inactivation of PI3K-AKT pathway in HESCs. Taken together, our study firstly demonstrates that MALAT1 regulates apoptosis of HESCs through miR-126-5p/CREB1 axis mediated PI3K/AKT pathway. Our findings explained the pathogenesis of endometriosis and offered promising therapeutic option for endometriosis.


Sex, rebellion and decadence: the scandalous evolutionary history of the human Y chromosome.
It can be argued that the Y chromosome brings some of the spirit of rock&roll to our genome. Equal parts degenerate and sex-driven, the Y has boldly rebelled against sexual recombination, one of the sacred pillars of evolution. In evolutionary terms this chromosome also seems to have adopted another of rock&roll's mottos: living fast. Yet, it appears to have refused to die young. In this manuscript the Y chromosome will be analyzed from the intersection between structural, evolutionary and functional biology. Such integrative approach will present the Y as a highly specialized product of a series of remarkable evolutionary processes. These led to the establishment of a sex-specific genomic niche that is maintained by a complex balance between selective pressure and the genetic diversity introduced by intrachromosomal recombination. Central to this equilibrium is the "polish or perish" dilemma faced by the male-specific Y genes: either they are polished by the acquisition of male-related functions or they perish via the accumulation of inactivating mutations. Thus, understanding to what extent the idiosyncrasies of Y recombination may impact this chromosome's role in sex determination and male germline functions should be regarded as essential for added clinical insight into several male infertility phenotypes. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.


In vivo distribution of organophosphate antidotes: autoradiography of [14C]HI-6 in the rat.
In order to visualize the distribution of HI-6 in the rat after iv administration, autoradiographic experiments were carried out with [14C]HI-6, labeled at the carbon of the carboxamide moiety. Autoradiography clearly confirms penetration of HI-6 into the central nervous system. Considerable radioactivity was found in the cerebrum, the cerebellum, and the choroid plexus. No significant activity was detected in the pontomedullary region or the spinal cord. Peripherally, [14C]HI-6 is observed in large amounts in kidneys, heart, liver, nose, bladder, testes, and marrow-containing bone. The gastrointestinal tract was largely devoid of any radioactivity. The relative absence of HI-6 in the pontomedullary region renders centrally mediated influences of HI-6 on hemodynamic and respiratory parameters less likely.


How Food Insecurity and Financial Difficulty Relate to Emotional Well-Being and Social Functioning.
Medically uninsured individuals living in poverty experience poor health and face social barriers that negatively affect their health. The purpose of this study was to examine the association between social barriers, particularly healthy food availability and financial difficulty, and well-being among uninsured free clinic patients in the United States. Data were collected using a self-administered paper survey at a free clinic from adult patients who spoke and read English or Spanish (N = 666) from January to April 2019. Better neighborhood healthy food availability is associated with better self-reported general health. Food security is related to better emotional well-being and social functioning. Having difficulty paying rent or a mortgage is linked to worse emotional well-being and social functioning. Providing health education programs may not be sufficient to promote healthy eating among underserved populations because of the social barriers that they experience, such as food insecurity and financial difficulty. Future research could be performed to determine how these social factors influence those of different social and cultural backgrounds than the participants in this study.


Superinduction of CYP1A1 transcription by cycloheximide. Role of the DNA binding site for the liganded Ah receptor.
Nuclear run-off experiments reveal that four distinct DNA domains, each of which contains a binding site for the liganded Ah receptor, can mediate the superinduction of transcription by 2,3,7,8-tetrachlorodibenzo-p-dioxin plus cycloheximide. Superinduction requires substantial inhibition of protein synthesis by cycloheximide. Gel retardation analyses of nuclear extracts and methylation protection studies in intact cells reveal no evidence for cycloheximide-sensitive protein-DNA interactions that might mediate the superinduction response. These observations suggest the existence of a labile protein(s) that acts to inhibit the function of the dioxin-responsive receptor/enhancer regulatory system via protein-protein interactions.


Study on prevention effect of Zishen Yutai pill combined with progesterone for threatened abortion in rats.
To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats. After pregnancy, 50 SPF female SD rats were selected and divided into control group, model group, progesterone group, Zishen Yutai pill group, and progesterone plus Zishen Yutai pill group (combination group), with 10 rats in each group. The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days. Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days. Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin, continuous for 10 days. Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days, and other treatments were the same as previous two groups. Abortion model were established then and live births, numbers of abortion and average rate of abortion were compared between the five groups. Peripheral blood was collected to detect the estradiol (E2) and progestational hormone (P), and obtain ratio of Th1/Th2 cytokines (IL-2, INF-γ, IL-4, IL-10). Significant more live births of rats were found in the control group compared with other four groups (P < 0.05) (P < 0.05). The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group, Zishen Yutai pill group and joint group (P < 0.05). The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group. The serum E2 level of P of rats in the control group, progesterone group, Zishen Yutai pill group and joint group were significant higher than that of abortion model group (P < 0.05). Serum levels of E2 and P of rats in the control group, progesterone group, Zishen Yutai pill group and joint group were not significant different (P > 0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group (P < 0.05). The maternal-fetal interface IL - 4/IL - 2, IL - 10/IL - 2 of model group were balanced deviating to Th1, while the IL-4/IL-2, IL-10/IL-2 of progesterone group, Zishen Yutai pill group and joint group were balanced deviating to Th2, and joint group' deviation was better than progesterone group and Zishen Yutai pill group (P < 0.05). Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion, which can obviously increase contents of maternal serums E2 and P, and regulate the Th1/Th2 balance with a remarkable effect.


Chronotropic incompetence and its relation to exercise intolerance in hypertrophic cardiomyopathy.
Diminished functional capacity is common in hypertrophic cardiomyopathy (HCM), although the underlying mechanisms are complicated. We studied the prevalence of chronotropic incompetence and its relation to exercise intolerance in patients with HCM. Cardiopulmonary exercise testing was performed in 68 patients with HCM (age 44.8 ± 14.6 years, 45 males). Chronotropic incompetence was defined by chronotropic index (heart rate reserve)/(220-age-resting heart rate) and exercise capacity was assessed by peak oxygen consumption (peak Vo(2)). Chronotropic incompetence was present in 50% of the patients and was associated with higher NYHA class, history of atrial fibrillation, higher fibrosis burden on cardiac MRI, and treatment with β-blockers, amiodarone and warfarin. On univariate analysis, male gender, age, NYHA class, maximal wall thickness, left atrial diameter, peak early diastolic myocardial velocity of the lateral mitral annulus, history of atrial fibrillation, presence of left ventricular outflow tract obstruction (LVOTO) at rest, and treatment with beta-blockers were related to peak Vo(2). Peak heart rate during exercise, heart rate reserve, chronotropic index, and peak systolic blood pressure were also related to peak Vo(2). On multivariate analysis male gender, atrial fibrillation, presence of LVOTO and heart rate reserve were independent predictors of exercise capacity (R(2) = 76.7%). A cutoff of 62 bpm for the heart rate reserve showed a negative predictive value of 100% in predicting patients with a peak Vo(2) <80%. Blunted heart rate response to exercise is common in HCM and represents an important determinant of exercise capacity.


The first successful crystallographic characterization of a cyclodextrin dimer: efficient synthesis and molecular geometry of a doubly sulfur-bridged beta-cyclodextrin.
Beta-cyclodextrin is transannularly disulfonylated at the 6(A)- and 6(B)-positions, and then converted to the corresponding 6(A),6(B)-diiodide and 6(A),6(B)-dithiol. Cross-coupling of the latter two species yields a single head-to-head-coupled beta-cyclodextrin dimer 5 with two sulfur linkers at adjacent 6-methylene carbons. NMR and X-ray analysis revealed the trans-type ("aversive") linkage of both beta-cyclodextrin units. In the solid-state structure of 5.5 MeOH.23 H(2)O, the undistorted cyclodextrin macrocycles feature almost parallel ring planes pointing away from each other, leaving 5 with a "handcuff-like" appearance of approximate C(2) symmetry. This work represents the first successful crystallographic study on a cyclodextrin dimer.


Clinical course of Crohn's disease first diagnosed at surgery for acute abdomen.
The severity of clinical activity of Crohn's disease is high during the first year after diagnosis and decreases thereafter. Approximately 50% of patients require steroids and immunosuppressants and 75% need surgery during their lifetime. The clinical course of patients with Crohn's disease first diagnosed at surgery has never been investigated. To assess the clinical course of Crohn's disease first diagnosed at surgery for acute abdomen and to evaluate the need for medical and surgical treatment in this subset of patients. Hospital clinical records of 490 consecutive Crohn's disease patients were reviewed. Patients were classified according to the Vienna criteria. Sex, extraintestinal manifestations, family history of inflammatory bowel diseases, appendectomy, smoking habit and medical/surgical treatments performed during the follow-up period were assessed. Kaplan-Meier survival method and Cox proportional hazards regression model. Of the 490 Crohn's disease patients, 115 had diagnosis of Crohn's disease at surgery for acute abdomen (Group A) and 375 by conventional clinical, radiological, endoscopic and histologic criteria (Group B). Patients in Group A showed a low risk of further surgery (Log Rank test p<0.001) and a longer time interval between diagnosis and first operation compared to Group B (10.8 years vs. 5.8 years, p<0.01, respectively). Furthermore, patients in Group A used less steroids and immunosuppressants (OR 0.3, p<0.0001; OR 0.6, p<0.004, respectively). Crohn's disease patients first diagnosed at surgery for acute abdomen showed a low risk for reintervention and less use of steroids and immunosuppressants during follow-up than those not operated upon at diagnosis. Early surgery may represent a valid approach in the initial management of patients with Crohn's disease, at least in the subset of patients with ileal and complicated disease.


Maternal metabolic status and in-vitro culture conditions during embryonic genome activation deregulate the expression of energy-related genes in the bovine 16-cells embryo.
The molecular consequences of the metabolic stress caused by milk production of dairy cows in the early embryo are largely unknown. The objective was to determine the impact of dam metabolic status or in vitro culture during embryonic genome activation (EGA) on the transcriptomic profiles of bovine 16-cell stage embryos. Two days after synchronized oestrus, in vitro produced 2- to 4-cell stage embryos were endoscopically transferred in pools of 50 into the oviduct ipsilateral to the corpus luteum of lactating (LACT, n = 3) or nonlactating (i.e. dried off immediately at calving; DRY, n = 3) dairy cows. On Day 4, the oviducts were flushed to recover the embryos. Pools of five Day-2 embryos (n = 5) and Day-4 16-cell stage embryos obtained in vitro (n = 3) or from LACT or DRY cows were subjected to RNAseq. Temporally differentially expressed genes (DEG; FDR<0.05) between Day-2 and Day-4 embryos were determined considering the differences between the three conditions under which EGA occurred. Also, DEG between Day-4 embryos derived from the three conditions were identified. Functional analysis of the temporal DEG demonstrated that genes involved in ribosome, translation and oxidative phosphorylation in the mitochondria were strongly more expressed in Day-4 than Day-2 embryos. Comparison of Day-4 embryos that underwent EGA in vitro, or in LACT or DRY cows, identified DEG enriching for mitochondrial respiration and protein translation, including the mTOR pathway. In conclusion, exposure of the embryo to an unfavourable maternal metabolic status during EGA influences its transcriptome and potentially the competence for pregnancy establishment.


Raman spectroscopy: a structural probe of glycosaminoglycans.
We report the first Raman spectroscopic study of the glycosaminoglycans chondroitin 4-sulfate, chondroitin 6-sulfate and hyaluronic acid, both in solution and in the solid state. To aid in spectral identification, infrared spectra were also recorded from films of these samples. Vibrational frequencies for important functional groups like the sulfate groups, glycosidic linkages, C-OH and the N-acetyl group can be identified from the Raman spectra. Certain differences in the spectra of the different glycosaminoglycans can be interpreted in terms of the geometry of the various substituents, while other differences can be related to differences in chemical composition.