Imparied thermal regulation in juvenile rats following perinatal methadone exposure.
Offspring of female rats injected daily with methadone (5 mg/kg) or saline were cross-fostered at birth to form groups exposed to methadone during gestation (G), lactation (L), or gestation and lactation (G-L); controls (C) were exposed only to saline. Rectal temperature, body weight and food consumption were measured from postnatal Days 36-51. Ambient temperature was maintained at 21 degrees C except for Days 42--45, when the temperature was 10 degrees C. Group G rats never differed from controls, but offspring in Groups L and G-L were hypothermic at room temperature; Group G-L rats exhibited a further temperature loss during the cold stress. There were no group differences in food consumption after Day 39, and all groups increased food intake while in the cold. Group differences in body weight were not reliable but Group G-L rats gained less weight than the rest during the experiment, whereas Group L rats gained more. These results indicate that, depending upon treatment schedule, perinatal methadone exposure is associated with hypothermia during the postweaning period. A prolonged withdrawal reaction from methadone may account for the impaired thermal regulation.


Parkinson's disease kinase LRRK2 coordinates a cell-intrinsic itaconate-dependent defence pathway against intracellular Salmonella.
Cell-intrinsic defences constitute the first line of defence against intracellular pathogens. The guanosine triphosphatase RAB32 orchestrates one such defence response against the bacterial pathogen Salmonella, through delivery of antimicrobial itaconate. Here we show that the Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2) orchestrates this defence response by scaffolding a complex between RAB32 and aconitate decarboxylase 1, which synthesizes itaconate from mitochondrial precursors. Itaconate delivery to Salmonella-containing vacuoles was impaired and Salmonella replication increased in LRRK2-deficient cells. Loss of LRRK2 also restored virulence of a Salmonella mutant defective in neutralizing this RAB32-dependent host defence pathway in mice. Cryo-electron tomography revealed tether formation between Salmonella-containing vacuoles and host mitochondria upon Salmonella infection, which was significantly impaired in LRRK2-deficient cells. This positions LRRK2 centrally within a host defence mechanism, which may have favoured selection of a common familial Parkinson's disease mutant allele in the human population.


A comparison of the pulmonary toxicity and chemotherapeutic activity of bleomycin-BAPP to bleomycin and pepleomycin.
The pulmonary toxicity and antitumor activity of a new bleomycin analog butylamino-3-propylamino-3-propylamine (Blm-BAPP) was investigated and compared with bleomycin and pepleomycin. Blm-BAPP was significantly more pulmonary toxic than bleomycin and had no greater activity against B16 melanoma than either bleomycin or pepleomycin. Although pepleomycin was as equitoxic as bleomycin in producing pulmonary fibrosis, doses of pepleomycin greater than 5 mg/kg were more lethal than bleomycin. Not only did the three drugs function similarly in vivo, but they behaved similarly in two in vitro test systems: microsome-catalyzed drug-mediated DNA deoxyribose cleavage and binding to DNA.


Factors influencing the responsiveness to inhaled glucocorticoids of patients with moderate-to-severe asthma.
Inhaled glucocorticoids (GCs) are the most effective control therapy for asthma. Although the clinical effects of inhaled GCs vary, there are few data on the differences in the responsiveness of individuals to inhaled GCs. The purpose of this study was to identify those factors that are associated with responsiveness to high-dose inhaled GCs in patients with moderate-to-severe asthma. This study was a prospective analysis. Outpatient clinics of tertiary hospitals. Eighty-six adult outpatients with moderate-to-severe asthma. Eighty-six patients with asthma who had initial FEV1 values of < 80% predicted after they had received inhaled GCs (fluticasone propionate, 1,000 microg/d) for 4 weeks. The primary end points were FEV1, FEV1/FVC ratio, forced expiratory flow (midexpiratory phase), and the score at presentation in the asthma-related quality-of-life questionnaire (AQLQ). The inhalation of GCs for 4 weeks had significant improvements in the FEV1% predicted and in the AQLQ score compared with the baseline values. Asthmatic patients with responses of > 12% (n = 46, 53.4%) in the change in FEV1 (deltaFEV1 = [FEV1 at 4 weeks--baseline FEV1]/baseline FEV1 x 100) also had significantly higher proportions of blood eosinophils and lower FEV1 values (in liters) prior to treatment. The change in FEV1 values correlated with the number of sputum eosinophils prior to GC inhalation (r = 0.242; p < 0.05) and correlated inversely with the FEV1 percent predicted values prior to GC inhalation (r = -0.462; p < 0.001). The FEV1 percent predicted and the blood and sputum eosinophil levels prior to GC inhalation are associated with the responsiveness to inhaled GCs in patients with moderate-to-severe asthma.


Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers.
The clinical outcome of contralateral prophylactic mastectomy (CPM) in women with a BRCA1 or BRCA2 mutation and a personal history of invasive breast cancer is unknown. We identified a cohort of 148 female BRCA1 or BRCA2 mutation carriers (115 and 33, respectively) who previously were treated for unilateral invasive breast cancer stages I-IIIa. In all, 79 women underwent a CPM, while the other women remained under intensive surveillance. The mean follow-up was 3.5 years and started at the time of CPM or at the date of mutation testing, whichever came last, that is, on average 5 years after diagnosis of the first breast cancer. One woman developed an invasive contralateral primary breast cancer after CPM, whereas six were observed in the surveillance group (P<0.001). Contralateral prophylactic mastectomy reduced the risk of contralateral breast cancer by 91%, independent of the effect of bilateral prophylactic oophorectomy (BPO). At 5 years follow-up, overall survival was 94% for the CPM group vs 77% for the surveillance group (P=0.03), but this was unexpectedly mostly due to higher mortality related with first breast cancer and ovarian cancer in the surveillance group. After adjustment for BPO in a multivariate Cox analysis, the CPM effect on overall survival was no longer significant. Our data show that CPM markedly reduces the risk of contralateral breast cancer among BRCA1 or BRCA2 mutation carriers with a history of breast cancer. Longer follow-up is needed to study the impact of CPM on contralateral breast cancer-specific survival. The choice for CPM is highly correlated with that for BPO, while only BPO leads to a significant improvement in overall survival so far.


Highlights from the history of hormonal cytology.
In 1847 Felix-Archimede Pouchet effectively launched the study of the physiology of cytology. Now 160 years later, the authors briefly trace the development of hormonal cytology to our present knowledge and practice. In the course of the paper the contribution of George Papanicolaou is stressed because of his monumental contribution to a major segment of medical practice of great emotive import.


The effectiveness of immunomodulatory therapies for patients with repeated implantation failure: a systematic review and network meta-analysis.
This meta-analysis analyzed the clinical pregnancy outcomes of repeated implantation failure (RIF) patients treated with immunomodulatory therapies. Publications (published by August 16, 2021) were identified by searching the PubMed, Embase, and Web of Science databases. The quality of the studies was evaluated with the Cochrane bias risk assessment tool, and a network meta-analysis was performed with Stata 14.0. The outcomes were clinical pregnancy rate (CPR), live birth rate (LBR), and implantation rate (IR). The results of our network meta-analysis of 16 RCTs (including 2,008 participants) show that PBMCs, PRP, and SC-GCSF can significantly improve the CPR compared with LMWH (PBMCs: OR 2.15; 95% CI 1.21-3.83; PRP: OR 2.38; 95% CI 1.08-5.24; SC-GCSF: OR 2.46; 95% CI 1.05-5.72). The LBR of PRP was significantly higher than those of IU-GCSF (OR 3.81; 95% CI 1.22-11.86), LMWH (OR 4.38; 95% CI 1.50-12.90), and intralipid (OR 3.85; 95% CI 1.03-14.29), and the LBR of PBMCs was also significantly better than that of LMWH (OR 2.35; 95% CI 1.14-4.85). Furthermore, PRP treatment significantly improved the IR compared with LMWH treatment (OR 2.81; 95% CI 1.07-7.4). The limited evidence from existing RCTs suggests that PBMCs and PRP are the best therapeutic options for RIF patients. However, owing to the quantity limitation, more top-quality research is required to obtain additional high-level evidence.


Acute Neurological Complications of Coronavirus Disease.
The coronavirus disease (COVID-19) pandemic has impacted many lives globally. Neurologic manifestations have been observed among individuals at various stages and severity of the disease, the most common being stroke. Prompt identification of these neurologic diagnoses can affect patient management and prognosis. This article discusses the acute neuroradiological features typical of COVID-19, including cerebrovascular disease, intracerebral hemorrhage, leukoencephalopathy, and sensory neuropathies.


Myelination of a fetus with Pelizaeus-Merzbacher disease: immunopathological study.
We report an autopsied case of a 21-gestational-week fetus with duplication of the proteolipid protein (PLP) gene (PLP1). An immunohistochemical study, which can detect the specific expression of PLP, myelin basic protein, myelin-associated glycoprotein, and platelet-derived growth factor receptor alpha subunit in brain tissues, showed that the myelination was almost the same as that of age-matched controls. This result suggests that the development and migration of the oligodendrocyte is normal in Pelizaeus-Merzbacher disease until midgestation. To our knowledge, this is the first report of the myelination of a fetus with duplication of the PLP1 gene.


A Case of Atraumatic, Streptococcal Pneumocephalus: A Rare Complication of Influenza B Infection.
BACKGROUND Pneumocephalus is a rare occurrence without trauma, neurosurgery, or intracranial pathology. It is an uncommon complication of bacterial meningitis, and it is usually diagnosed with a CT head. Bacterial pneumocephalus in the setting of influenza B virus infection is an extremely rare complication; however, vaccination against influenza and early diagnosis and treatment help prevent mortality. CASE REPORT A 51-year-old woman presented to the Emergency Department in early winter because of worsening mental status over seven days prior to presentation. She was not vaccinated against influenza. Before and upon presentation to our facility, she was diagnosed with influenza B virus infection and was positive for streptococcal meningitis. A CT head revealed pneumocephalus, likely due to Streptococcus infection. She was treated with antibiotics, and a repeat CT head showed resolution of the lesion. CONCLUSIONS Bacterial pneumocephalus in the background of influenza is an uncommon occurrence. Influenza vaccination and early diagnosis with a CT of the head and prompt initiation of antibiotics are essential in preventing mortality.


Plant uptake and transport models for neutral and ionic chemicals.
Models for predicting uptake and transport of chemicals in plants are applied in pesticide design, risk assessment, and environmental biotechnology. This review considers the theoretical basics of the most popular models, and discusses what they have in common. The line is drawn between models for neutral compounds, and models for weak and strong electrolytes. Neutral Compounds. Neutral compounds undergo only very few processes inside plants (lipophilic interactions, metabolism), in contrast to weak electrolytes. The models developed for neutral compounds are widely applied in the risk assessment of environmental contaminants, but are not of much use for weak electrolytes, such as pesticides. Weak electrolytes. A very important process for weak electrolytes is the 'ion trap', which traps chemicals that dissociate inside plant cells. This is considered in the popular models of Kleier, Satchivi and Briggs. Other relevant processes for electrolytes are electrophilic interactions, speciation and complex formation. None of the currently used models considers these processes. The accuracy of models for neutral compounds is satisfactory, but the prediction of electrolyte behavior inside plants is still quite difficult due to gaps in knowledge.


Self and non-self antigen in diabetic autoimmunity: molecules and mechanisms.
In this article, we have summarized current facts, models and views of the autoimmunity that leads to destruction of insulin-producing beta-cells and consequent Type 1 (insulin-dependent) diabetes mellitus. The presence of strong susceptibility and resistance gene loci distinguishes this condition from other autoimmune disorders, but environmental disease factors must conspire to produce disease. The mapping of most of the genetic risk (or disease resistance) to specific alleles in the major histocompatibility locus (MHC class II) has direct functional implications for our understanding of autoimmunity in diabetes and directly implies that presentation of a likely narrow set of peptides is critical to the development of diabetic autoimmunity. While many core scientific questions remain to be answered, current insight into the disease process is beginning to have direct clinical impact with concerted efforts towards disease prevention or intervention by immunological means. In this process, identification of the critical antigenic epitopes recognized by diabetes-associated T cells has achieved highest priority.


Seasonal variations, temperature dependence, and sources of size-resolved PM components in Nanjing, east China.
Size-segregated ambient particulate matter (PM) samples were collected seasonally in suburban Nanjing of east China from 2016 to 2017 and chemically speciated. In both fine (< 2.1 µm, PM2.1) and coarse (> 2.1 µm, PM>2.1) PM, organic carbon (OC) accounted for the highest fractions (26.9% ± 10.9% and 23.1% ± 9.35%) of all measured species, and NO3- lead in average concentrations of water-soluble inorganic ions (WSIIs). The size distributions of measured components were parameterized using geometric mean diameter (GMD). GMD values of NO3-, Cl-, OC, and PM for the whole size range varied from < 2.1 µm in winter to > 2.1 μm in warm seasons, which was due to the fact that the size distributions of semi-volatile components (e.g., NH4NO3, NH4Cl, and OC) had a dependency on the ambient temperature. Unlike OC, elemental carbon (EC), and elements, NH4+, NO3-, and SO42- exhibited an increase trend in GMD values with relative humidity, indicating that the hygroscopic growth might also play a role in driving seasonal changes of PM size distributions. Positive matrix factorization was performed using compositional data of fine and coarse particles, respectively. The secondary formation of inorganic salts contributing to the majority (> 70%) of fine PM and 20.2% ± 19.9% of speciated coarse PM. The remaining coarse PM content was attributed to a variety of dust sources. Considering that coarse and fine PM had comparable mass concentrations, more attention should be paid to local dust emissions in future air quality plans.


Efficacy of a combination febantel-praziquantel-pyrantel product, with or without vaccination with a commercial Giardia vaccine, for treatment of dogs with naturally occurring giardiasis.
To determine efficacy of treatment with a combination febantel-praziquantel-pyrantel product, with or without vaccination with a commercial Giardia vaccine, in dogs with naturally occurring giardiasis. Prospective trial. 16 Beagles naturally infected with Giardia duodenalis. During phase 1, 6 dogs were treated with the parasiticide for 3 days (4 were also vaccinated). Four weeks later, all 6 dogs were treated with the parasiticide again for 5 days and were bathed and moved to clean cages after the last treatment (phase 2). Nine dogs were treated with the parasiticide for 3 (n = 4) or 5 (5) days and bathed and moved to clean cages after the last treatment (phase 3). Fecal samples were collected twice weekly for 24 days after treatment and tested for cysts with a quantitative zinc sulfate flotation technique and for Giardia antigen with an immunoassay. Dogs in phase 1 were all shedding cysts again by day 24. In phase 2, only 1 dog shed cysts after treatment, and shedding was transient (day 17). In phase 3, neither cysts nor antigen was detected in fecal samples from 2 of 4 dogs treated for 3 days and 4 of 5 dogs treated for 5 days. In 18 of 57 (31.6%) fecal samples, cysts were seen, but results of the immunoassay were negative. Results suggest that when a combination febantel-praziquantel-pyrantel product is used to treat dogs with giardiasis, bathing and changing the environment after treatment may be more important in preventing recurrence than duration of treatment.


Sonographic-detected joint effusion compared with physical examination in the assessment of sacroiliac joints in spondyloarthritis.
An observational case-control study was designed to analyse the discriminative value of ultrasound (US)-detected joint effusion compared with physical examination in the assessment of sacroiliac joints (SIJ) in patients with spondyloarthropathy (SpA) with or without inflammatory back pain (IBP). 45 patients with SpA, classified according to European Spondylarthropathy Study Group criteria, and 30 healthy volunteers were studied. All patients had clinical evaluation of the SIJ, Bath ankylosing spondylitis (AS) metrology index, Bath AS disease activity index, Bath AS functional index, health assessment questionnaire, patient's and physician's visual analogue scale on global disease activity. Ultrasound showed joint effusion in 38.9% of SIJ of patients with SpA and in 1.7% of SIJ of controls (p<0.001). The presence of IBP was significantly associated with SIJ effusion assessed by US alone or plus at least one SIJ test. SIJ effusion assessed by US alone or plus at least one SIJ test had a positive likelihood ratio (LR) (2.67 and 4.04, respectively) for the presence of IBP higher than LR of single clinical tests. Positive sacral sulcus test, iliac gapping and midline sacral thrust test were associated with SIJ effusion assessed by US, but all clinical tests, singly and in various combinations, had a low LR for the presence of SIJ effusion assessed by US. The study suggests that high resolution sonography is useful in the assessment of SIJ involvement in SpA, resulting in images that are fast and inexpensive and may locate, complementing the physical examination, the origin of IBP.


BVDV, BHV-1 and BLV antibodies in dromedary camels of Turkey kept without and with ruminants.
Camels are the only animals bred to sustain the tradition of wrestling in Turkey and are reared within a limited set of geographic areas. Farmers of such animals may also be engaged in ruminant breeding. The current research was aimed at documenting bovine viral diarrhoea virus (BVDV), bovine herpesvirus-1 (BHV-1), and bovine leukaemia virus (BLV) infections in sera collected from dromedary camels in four different geographical regions of Turkey during the years 2019-2021. All samples were tested for BVDV, BHV-1 and BLV antibodies as well as BVDV antigen by ELISA. Antibodies against BVDV were found in 16.8% of the camel sera tested. However, none of the camels sampled were positive in terms of BHV-1 and BLV antibodies as well as BVDV antigen. The prevalence was observed higher in the herds in which ruminants were raised in addition to camels (OR = 4.583, 95% CI, 1.298-16.182), (p = 0.018), while the prevalence was observed lower in the herds in which only camels were raised. This study showed that BVDV infection was more prevalent than BHV-1 and BLV infections in Turkish dromedary camels. Herewith, the camels, being a susceptible species to numerous viral ruminant diseases, may also serve as an important source of BVDV infection for other ruminant animals in the same flock.


The kinetics of extraamniotically injected prostaglandins to induce midtrimester abortion.
In an attempt to improve the extraamniotic administration of prostaglandins in effecting abortion, the movement of injected prostaglandins in a high or low viscosity medium has been observed by radiological studies and radioimmunoassy of PGE and PGFalpha in amniotic fluid and maternal plasma in association with intrauterine tocographic responses. Results obtained suggest that the immediate response by the uterus is a reflection of the speed of absorption of prostaglandins from the chorio-decidual space and that this influences the outcome in inducing abortion within 24 hours. By giving the prostaglandins in a viscous medium a slower release of prostaglandins was produced in most cases, which probably accounts for the greater efficacy obtained using single injections of prostaglandins in this vehicle compared with normal saline.


Comparison of the dynamics and functional redundancy of the Arabidopsis dynamin-related isoforms DRP1A and DRP1C during plant development.
Members of the Arabidopsis (Arabidopsis thaliana) DYNAMIN-RELATED PROTEIN1 (DRP1) family are required for cytokinesis and cell expansion. Two isoforms, DRP1A and DRP1C, are required for plasma membrane maintenance during stigmatic papillae expansion and pollen development, respectively. It is unknown whether the DRP1s function interchangeably or if they have distinct roles during cell division and expansion. DRP1C was previously shown to form dynamic foci in the cell cortex, which colocalize with part of the clathrin endocytic machinery in plants. DRP1A localizes to the plasma membrane, but its cortical organization and dynamics have not been determined. Using dual color labeling with live cell imaging techniques, we showed that DRP1A also forms discreet dynamic foci in the epidermal cell cortex. Although the foci overlap with those formed by DRP1C and clathrin light chain, there are clear differences in behavior and response to pharmacological inhibitors between DRP1A and DRP1C foci. Possible functional or regulatory differences between DRP1A and DRP1C were supported by the failure of DRP1C to functionally compensate for the absence of DRP1A. Our studies indicated that the DRP1 isoforms function or are regulated differently during cell expansion.


Vibratory coherence as an alternative to radiography in assessing bone healing after osteodistraction.
Distraction osteogenesis is used in orthopedics to lengthen bones by cutting or breaking the bone and gradually separating the two pieces as new bone fills the intervening space. There is a need for early assessment of the degree of bone healing that allows for normal functioning without unwanted side effects. This study compared different techniques used to evaluate the degree of bone healing during mandibular osteodistraction in 21 rabbits. For each rabbit, the mandible was cut in a surgical procedure and then 72 h later distraction began at a rate of 3 mm per day. Bone formation at the distraction site was assessed by in vivo photodensitometry on head radiographs, an in vivo (nondestructive) vibratory coherence test across the distraction site, a postmortem, ex vivo (destructive) three-point bending mechanical test, and by postmortem, ex vivo (destructive) histological examination. Statistical analyses included analysis of variance and correlation coefficient tests. The findings revealed that the results of bone photodensity and the mechanical three-point test are highly and positively correlated with the results of the vibration test. The use of the vibration test may provide a substitute for or augment the routine use of radiography for in vivo evaluation and monitoring of bone healing.


Effect of adhesive systems and bevel on enamel margin integrity in primary and permanent teeth.
This study compared the effectiveness of self-etch and total-etch adhesive systems in bonding to the beveled and nonbeveled margins of primary and permanent teeth. This in vitro, factorial-designed study allowed evaluation of 3 factors: (1) tooth type; (2) presence of a bevel; and (3) adhesive type. Two preparations, each including a beveled and nonbeveled margin, were completed on buccal surfaces of 60 extracted molars (30 primary and 30 permanent). Preparations were randomly assigned to self-etch or a total-etch adhesive system and restored with resin composite. After thermocycling, teeth were stained with silver nitrate, sectioned, and measured for microleakage. Statistical analysis used a repeated measures analysis of variance. Beveled margins had less microleakage than nonbeveled margins for primary and permanent teeth (P < .001). Total-etch had less microleakage than self-etch adhesives on primary (53% less, P < .001) and on permanent teeth (22% less, P = .01). Self-etch had considerably more microleakage when enamel margins were not beveled. Comparably less microleakage, however, was found for total-etch and self-etch in restorations with beveled margins. Total-etch adhesive and beveled margins resulted in the least microleakage. Margin beveling has a greater effect in minimizing microleakage than the type of adhesive used.


Discovery of keratinases using bacteria isolated from marine environments.
Bacteria are important for the biodegradation of keratin. Thus, a workflow to isolate keratin-degrading bacteria utilizing an optimized azo-keratin assay was established. Deteriorated feather samples, collected in marine shoreline environments from the intertidal zone, yielded 50 unique bacterial isolates exhibiting keratin degradation when feather meal was supplied as keratin substrate. The majority of isolates, identified by 16S sequencing, belonged to genera previously reported to produce keratinases: Bacillus spp. (42%) and Stenotrophomonas spp. (40%). The remaining 18% represented the genera Alcaligenes, Chryseobacterium, Salinivibrio, Delftia, Stappia, and Microbacterium, genera not previously been associated with keratinase production. The workflow, also applied to 21 Bacilli from our in-house culture collection, additionally revealed four Bacilli with remarkable feather degradation potential. The industrial applicability of their associated keratinases was evaluated and the most active keratinase expressed in E. coli to confirm keratinase expression. Enriched keratinase fractions demonstrated activity up to 75°C and retained viability when stored lyophilized at 20°C for up to 200d.


Magnesium administration reverses the hypocalcaemia secondary to hypomagnesaemia despite low circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D.
The effect of parenteral administration of magnesium was studied in five patients with hypomagnesaemic hypocalcaemia. The initial metabolic state was characterized by a normal level of serum immunoreactive parathyroid hormone (iPTH), and by low or undetectable serum 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25 (OH)2D). A parathyroid response was elicited by the acute intravenous injection of magnesium chloride. In contrast, 1,25(OH)2D did not change up to 24 h after the injection. Intramuscular magnesium sulphate restored serum magnesium and calcium to normal, whereas iPTH was transiently increased. 25OHD remained low and unchanged. 1,25(OH)2D rose very slowly, but the correction of hypocalcemia began before any change in 1,25(OH)2D levels could be demonstrated. Thus, the early correction of hypocalcemia mainly depended on the restoration of an adequate parathyroid function independently of the secretion of 1,25(OH)2D.


Dural hemorrhage of the tentorium on postmortem cranial computed tomographic scans in children.
We analyzed four children with increased density of the tentorium on postmortem computed tomographic (CT) scans that suggested traumatic subarachnoid hemorrhage; but in which followup autopsy demonstrated an absence of subarachnoid hemorrhage. All cases had neither head injuries nor distinct intracranial abnormalities. Histological examinations showed extensive hemorrhage within the tentorium. These findings indicate that increased density of the tentorium on postmortem CT scan reflects 'dural hemorrhage' that may occur in children without intracranial abnormalities. Pediatricians and forensic pathologists should be aware of this phenomenon when using postmortem preautopsy CT scanning for diagnosis of child abuse.


Impact of malondialdehyde-modified low-density lipoprotein on clinical outcomes after fractional flow reserve-guided deferral of revascularization.
Cardiovascular events can occur after deferred revascularization, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) has been suggested to be an atherogenic marker. We investigated the relationship between serum MDA-LDL levels and clinical outcomes in patients with fractional flow reserve (FFR)-guided deferral of revascularization. Among 3084 patients undergoing coronary angiography, we retrospectively analyzed 127 patients with intermediate stenosis and deferred revascularization based on FFR > 0.80. Median follow-up interval was 30.4 months, and serum MDA-LDL was measured prior to the measurement of FFR. We evaluated the composite of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, ischemia-driven deferred lesion revascularization, and any revascularization. MACEs occurred in 18 (14.2%) patients. The MACE group presented with significantly higher MDA-LDL levels than the non-MACE group (134.9 ± 33.3 U/L vs. 95.6 ± 32.2 U/L, P < 0.001). In analysis of the receiver operating characteristics curve for the prediction of MACEs, MDA-LDL presented a significantly larger area under the curve than low-density lipoprotein-cholesterol (LDL-C; 0.810 vs. 0.687, P = 0.042). Univariate Cox regression analysis indicated a significant relationship between MACEs and MDA-LDL (per 10 U/L, HR 1.20; P = 0.004), as did the multivariate model (per 10 U/L, HR 1.17; P = 0.019). When compared according to the median LDL-C (98 mg/dL), the MACE group had significantly higher MDA-LDL in both the high (147.2 ± 27.3 U/L vs. 113.9 ± 31.2 U/L, P = 0.001) and low (103.2 ± 27.3 U/L vs. 80.2 ± 24.0 U/L, P = 0.045) LDL-C groups. Serum MDA-LDL levels were associated with cardiac events in patients with deferral of revascularization based on FFR.


Selective herbivory by Christmas beetles in response to intraspecific variation in Eucalyptus terpenoids.
Between-tree variation in the terpenoid composition in the foliage of six species of Eucalyptus was investigated in relation to its effects on herbivory by Christmas beetles (Anoplognathus spp.). All six eucalypt species showed considerable intraspecific variation in terpenoid composition; the cineole content ranged from 13% to 78% of the total oil in different E. melliodora trees, from 0% to 67% in E. conica, 3% to 79% in E. sideroxylon, 1% to 76% in E. camaldulensis, 3% to 60% in E. rubida and 20% to 79% in E. blakelyi. Levels of defoliation by Christmas beetles of nine E. melliodora and eight E. conica trees were quantified from frass traps placed under each tree, and were used to confirm the reliability of visual ratings of defoliation. Defoliation was assessed visually for all six species and was found to be unrelated to the total amount of terpenoids in the foliage of each tree, but strongly associated with the percentage of cineole in the terpenoid mixture. Levels of most terpenoid components were significantly inter-correlated, so it was not possible to determine which components directly affected defoliation. The dominant Christmas beetle at all sites was A. montanus.


Trapping efficiency of three carnivorous Pinguicula species.
In situ trapping efficiencies of Pinguicula alpina L., P. villosa L., and P. vulgaris L. were compared with each other and with those of artificial traps at a subarctic site in northern Sweden. P. vulgaris had the highest trapping efficiency i.e., 21-37 μg prey trapped cm-2 day-1 and apparently has some means of attracting prey. The other two species trapped about 14-18 μg cm-2 day-1, a value similar to that of paper traps mimicing plant leaves. By weight, Nematocera and Collembola were the dominant groups trapped by P. alpina. P. villosa trapped mainly Collembola, while small Nematocera dominated the prey caught by P. vulgaris. Mites (Acarina) were caught in high numbers but contributed only a small part of the total captured biomass owing to their low weight.


Contralateral nodal failures in oropharyngeal cancers after TORS and unilateral neck management: a retrospective study.
Report the incidence of contralateral nodal failure rates in well-lateralized oropharyngeal carcinoma treated with upfront surgery and unilateral neck management. Lateralized oropharyngeal carcinomas treated with upfront surgery using transoral robotic surgery (TORS) and unilateral neck management (unilateral neck dissection ± unilateral radiation treatment) were identified. Primary endpoint was contralateral regional control (CRC). Secondary endpoints were local control (LC), and overall survival (OS). Thirty-two patients were included. Pathologic T categories included 66% pT1, 31% pT2 and 3% pT3. Nodal diseases comprised 41% N0 and 47% N1 (AJCC 8th). Twenty-three (72%) patients had HPV related tumors. 3-years CRC, LC and OS were 100%, 96% (89-100) and 96% (CI 89-100). One patient developed a second primary with contralateral nodal disease. Only one patient died from another primary cancer. In selected patients with lateralized oropharyngeal cancer, treatment with TORS and ipsilateral management of the neck may be oncologically safe without significant risk of contralateral failure. Level 2.


Function of a separate NH3-pore in Aquaporin TIP2;2 from wheat.
Functional analysis of heterologously expressed TaTIP2;2 by means of stopped-flow spectrometric studies provide evidence for water and ammonia conductivity. A series of experiments under increasing pH indicate that the gaseous NH(3), rather than the ammonium ion NH(4)(+) was transported. Results from inhibitor studies strongly suggest that NH(3) is not transported in file with water, but through a separate pathway, which could be supplied by the 5th central pore in a tetramer conformation.


Ultra-high resolution imaging of the human brain using acquisition-weighted imaging at 9.4T.
One of the main goals of ultra-high field MRI is to increase the spatial resolution reached in structural and functional images. Here, the possibility to obtain in vivo images of the human brain with voxel volumes below 0.02mm(3) is shown at 9.4T. To optimize SNR and suppress ringing artifacts, an acquisition-weighted 3D gradient-echo sequence is used, which acquires more averages in the center than in the outer regions of k-space. The weighting function is adjusted to avoid losses in spatial resolution and scan duration compared to a conventional experiment with an equal number of scans and otherwise identical parameters. Spatial resolution and SNR of the weighted sequence are compared to conventionally acquired images by means of phantom and in vivo measurements, and show improved image quality with unchanged spatial resolution and an SNR increase of up to 36% in phantoms and 20%±5% in vivo. Ultra-high resolution images with a voxel volume of 0.014mm(3) (0.13×0.13×0.8mm(3)) from the human brain have sufficient SNR and show fine intracortical detail, demonstrating the potential of the technique. The combination of acquisition-weighted imaging and highly sensitive array coils at ultra-high fields thus makes it possible to obtain images with ultra-high spatial resolutions within acceptable scan times.


Analysis of risk factors for duodenal leak after repair of a duodenal perforation.
Repairing of a duodenal perforation is a well accepted procedure, but clinically, approximately 4% of patients develop duodenal leaks after perforation repair, increasing the risk of death. We retrospectively analyzed clinical data from 168 patients at our hospital to explore risk factors for duodenal leak after perforation repair and developed a nomogram for predicting postoperative duodenal leak. This retrospective case-control study totalled 168 patients undergoing repair of a duodenal perforation with omentopexy at the General Surgery Department, Dongnan Hospital of Xiamen University, from January 2012 to January 2022. The patients were divided into the non-leak group and the leak group. Risk factors were evaluated by analyzing the patient's sex, shock, diameter and anatomic position of the ulcer, use of NSAIDS and Glucocorticoid, history of drinking, diabetes, chronic diseases, age, time of onset of symptoms and lab tests. One hundred fifty-six patients (92.9%) who did not develop leaks after repair of a duodenal perforation were included in the non-leak group, and 12 (7.1%) developed leaks were included in the leak group. In univariate analysis, there were significant differences between the two groups referring to age, shock, NSAIDs, albumin, and perforation size (P < 0.05). The area under the ROC curve for perforation diameter was 0.737, the p-value was 0.006, the optimal cutoff point was 11.5, sensitivity was 58.3%, and specificity was 93.6%, the positive predictive value is 41.1%, and the negative predictive value is 98.0%. In the internal validation of the performance of the nomogram, the C-index and AUC of the model were 0.896(95%CI 0.81-0.98), demonstrating that the nomogram model was well calibrated. The study discussed the risk factors for postoperative duodenal leak in patients undergoing repair of a duodenal perforation, and a nomogram was constructed to predict the leak. Future prospective studies with large sample sizes and multiple centres are needed to further elucidate the risk of duodenal leak after repair of a duodenal perforation.


Review and Meta-analysis on the Impact of the ADRA2A Variant rs1800544 on Methylphenidate Outcomes in Attention-Deficit/Hyperactivity Disorder.
Methylphenidate is among the most prescribed medications for treating attention-deficit/hyperactivity disorder (ADHD). However, nearly half of pediatric patients with ADHD do not respond to methylphenidate treatment. Pharmacogenetic testing can aid in identifying patients for whom methylphenidate is unlikely to be safe or effective, leading to improved methylphenidate outcomes and increased use of alternative treatment options for ADHD. This article aimed to summarize findings from studies of the ADRA2A gene variant, rs1800544, and its association with methylphenidate outcomes in ADHD. We systematically reviewed and meta-analyzed available literature on the impact of rs1800544 on methylphenidate outcomes in ADHD. Fourteen studies met inclusion criteria for review, 9 of which were eligible for meta-analysis. The included studies compared methylphenidate outcomes in patients with ADHD categorized by rs1800544 genotype. G-allele carriers experienced significantly greater improvements in ADHD symptom scores (Swanson, Nolan, and Pelham Version-IV Scale or ADHD Rating Scale-IV) relative to noncarriers (odds ratio 3.08, 95% confidence interval 1.71-5.56, p = .0002) and greater response rates as measured by a ≥50% improvement in symptom scores (odds ratio 2.68, 95% confidence interval 1.23-5.82, p = .01); no significant difference in response rate as measured by Clinical Global Impressions score ≤2 was found. Stouffer's z-score method showed significant improvement across all methylphenidate outcomes in G-allele carriers relative to noncarriers (z = 3.03, p = .002). These findings suggest that carriers of rs1800544 may have improved ADHD outcomes following methylphenidate treatment. However, the extent to which these improvements are clinically impactful remain unclear. Additional studies are required to determine if rs1800544 carrier status should influence clinical recommendations for treatment of ADHD symptoms.


The regulation of IgG4. 1. An immunoassay to detect bee venom specific IgG4 subclass levels.
Serum IgG consists of 4 subclasses designated IgG1-4. IgG subclasses have differing structures and different functions. The levels of antigen specific immunoglobulin in each of the subclasses is difficult to quantitate accurately but may be of significant diagnostic and therapeutic value. IgG4 constitutes approximately 4% of total IgG level in the serum. We describe an immunoassay which is highly sensitive and specific for IgG4 directed against bee venom. The assay can be performed in a routine diagnostic laboratory enhancing its value as a clinical tool. It is potentially useful in identifying patients who fail to respond to standard immunotherapy with bee venom. This immunoassay format can also be adapted to other antigens.


[Rotavirus, adenovirus, astrovirus, calicivirus and small round virus particles in feces of children with and without acute diarrhea, from 1987 to 1988, in the greater São Paulo].
Between 1987 and 1988, 193 faecal specimens from children, with or without diarrhea, were submitted to enzyme immunoassay, polyacrylamide-gel electrophoresis and electronmicroscopy tests for virus detection. The positivity for Rotavirus, Adenovirus, Astrovirus, Calicivirus and Small Round Virus Particles (SRVP) was 11.3%, 3.1%, 2.1%, 1.0% and 4.1%, respectively, for the 97 children with acute diarrhea. Of the 96 children without diarrhea, 4.2% were positive for Rotavirus, 1.0% for Calicivirus and 7.3% for SRVP. Of 15 positive specimens for Rotavirus, 14 showed electrophoretic patterns proper to group A and 1 specimen of group C Rotavirus. The analysis of electrophorotypes demonstrated great heterogeneity of electrophoretic patterns and predominance of subgroup 2, "long". The association of virus, bacteria and parasites was present both in children with or without acute diarrhea.


Isolation and identification of a new anti-inflammatory cyathane diterpenoid from the medicinal fungus Cyathus hookeri Berk.
A new cyathane diterpene, named as cyathin I (1), as well as two known cyathane diterpenes (12R)-11a,14a-epoxy-13a,14b,15-trihydroxycyath-3-ene (2) and erinacine I (3), were isolated from the liquid culture of Cyathus hookeri Berk. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compounds 1-3 showed inhibition against nitric oxide production in macrophages with an IC50 value of 15.5, 52.3, and 16.8 μM, respectively.


Emerging Role of Mitochondrial DNA as a Major Driver of Inflammation and Disease Progression.
Inflammation benefits the host by promoting the elimination of invading pathogens and clearance of cellular debris after tissue injury. Inflammation also stimulates tissue repair and regeneration to restore homeostasis and organismal health. Emerging evidence suggests that mitochondrial DNA (mtDNA), the only form of non-nuclear DNA in eukaryotic cells, is a major activator of inflammation when leaked out from stressed mitochondria. Here, we review the current understanding on the role of mtDNA in innate immunity, discussing how dysregulated mtDNA metabolism can promote chronic inflammation and disease progression.


Regional oxygen saturation measured by two different oximetry monitors in infants and children undergoing living donor liver transplantation with bilirubin measurements: A prospective observational study.
Tissue oximetry devices use wavelengths in the 680-870 nm range to separate between oxygenated/deoxygenated hemoglobin. Conjugated bilirubin has an absorption peak at 730 nm. We hypothesized that ForeSight Elite using 5 wavelengths reduces interference from bilirubin and shows higher regional tissue oxygen saturation (rSO2 ) than INVOS 5100C incorporating 2 wavelengths. Infants and children undergoing living donor liver transplantation were included between March 2019 and September 2020. Cerebral and somatic rSO2 were measured, and real-time simultaneous data were collected. Additionally, measurements were collected at (1) baseline, (2) beginning of dissection phase, (3) beginning of anhepatic phase, (4) reperfusion phase, and (5) skin closure. Bilirubin level was available at baseline and at reperfusion. Hyperbilirubinemia was defined as bilirubin level ≥1.0 mg/dl. Thirty-three patients with median age of 27 months and median weight of 12 kg were included. Baseline bilirubin levels were higher compared to values at reperfusion (p = .021). A linear mixed effects model considering bilirubin as fixed and patient as random effect showed that there was a statistically significant difference in cerebral rSO2 readings in function of time (p = .031), device (p < .001), and bilirubin concentrations (p = .007) but not for hemoglobin (p = .347), SpO2 (p = .882), and arterial partial pressure of CO2 (Pa CO2 ) (p = .146). The model showed that there was a statistically significant difference in somatic rSO2 readings in function of device (p < .001) and bilirubin concentrations (p = .023) but not for time (p = .074), hemoglobin (p = .954), SpO2 (p = .108), and Pa CO2 (p = .775). Bland-Altman plot analyzing cerebral and somatic rSO2 between both devices showed respectively a mean absolute bias and 95% limits of agreement of 21.73% (-10.21 to 53.67) and 19.52% (-29.51 to 68.54). Oximetry devices emitting light at >2 wavelengths may overcome interference from hyperbilirubinemia providing higher rSO2 readings.


Cell signaling, beyond cytosolic calcium in eukaryotes.
Calcium functions as a secondary messenger within the cytosols of eukaryotes. This serves as a reference point to evaluate three related questions:Exploration of these three interrelated questions indicates the importance of more sensitive techniques and of a refined concept of information transfer and transduction. 1. Calcium, as well as cyclic AMP, also functions as a paracrine messenger; how specific and extensive is this use? 2. Calcium binding proteins and calcium extrusion mechanisms have been identified in prokaryotes; does it function as a messenger? 3. The concentrations of other divalent cations, especially zinc and magnesium, are well regulated and perturbations have specific physiological impacts; are these divalents involved in information transfer? Exploration of these three interrelated questions indicates the importance of more sensitive techniques and of a refined concept of information transfer and transduction.


The effect of radiofrequency thermal capsulorrhaphy on glenohumeral translation, rotation, and volume.
The purpose of this study is to evaluate the effects of radiofrequency (RF) thermal capsulorrhaphy on the kinematic properties of the glenohumeral joint as determined by changes in resistance to multidirectional translational forces, alteration in the range of internal and external rotation, and changes in glenohumeral joint volume. Nonablative RF thermal energy was used to contract the glenohumeral joint capsule in 6 cadaveric shoulders. Measurements of translation were made after application of a 30-N load in anterior, posterior, and inferior directions. The maximum arc of internal and external rotation after application of a 1-N-m moment was also determined for vented specimens before and after thermal capsulorrhaphy. The percent reduction in glenohumeral capsular volume was measured by use of a saline solution injection-aspiration technique. Capsular shrinkage resulted in reductions in anterior, posterior, and inferior translation. The largest percent reductions in anterior translation were seen in external rotation at 45 degrees (48%, P <.05) and 90 degrees (41%, P <.05) abduction. For inferior translation, the largest percent reductions were seen in internal rotation at 45 degrees (40%, P <.05) and 90 degrees (45%, P <.05) abduction. Reductions in posterior translation were noted in internal rotation at 45 degrees (27%, P <.05) and 90 degrees (26%, P <.05) abduction. Other changes in translation were observed but were not statistically significant. The maximum arc of humeral rotation was reduced by a mean of 14 degrees at 45 degrees abduction and 9 degrees at 90 degrees abduction. The mean percent reduction in capsular volume for all shoulders was 37% (range, 8%-50%). This could not be correlated with percent reductions in translation and rotation. This study demonstrated the significant effect of RF thermal capsulorrhaphy in reducing glenohumeral multidirectional translation and volume with only a small loss of rotation in cadaveric shoulders.


Site- and orbital-dependent charge donation and spin manipulation in electron-doped metal phthalocyanines.
Chemical doping offers promise as a means of tailoring the electrical characteristics of organic molecular compounds. However, unlike for inorganic semiconductors used in electronics applications, controlling the influence of dopants in molecular complexes is complicated by the presence of multiple doping sites, electron acceptor levels, and intramolecular correlation effects. Here we use scanning tunnelling microscopy to analyse the position of individual Li dopants within Cu- and Ni-phthalocyanine molecules in contact with a metal substrate, and probe the charge transfer process with unprecedented spatial resolution. We show that individual phthalocyanine molecules can host at least three distinct stable doping sites and up to six dopant atoms, and that the ligand and metal orbitals can be selectively charged by modifying the configuration of the Li complexes. Li manipulation reveals that charge transfer is determined solely by dopants embedded in the molecules, whereas the magnitude of the conductance gap is sensitive to the molecule-dopant separation. As a result of the strong spin-charge correlation in confined molecular orbitals, alkali atoms provide an effective way for tuning the molecular spin without resorting to magnetic dopants.


Radiosensitization by misonidazole during recovery of cellular thiols following depletion by BSO or DEM.
V79 cells have been depleted of their endogenous thiols by treatment with 100 microM BSO for 16-18 hr, or 0.5 mM DEM for 1 hr. The recovery of cellular thiols after removal of the drugs was determined by h.p.l.c. or flow cytometry and the sensitizer enhancement ratio for 100 microM misonidazole was measured as a function of time after removal of the drugs. The SER of 1.2 for control (hypoxic) cells increased to 1.8 for BSO treated (hypoxic) cells and 2.2 for DEM treated ones, when thiol levels were below 10% of controls. The SER and thiol levels returned to control values within 5 hr of removing DEM. After BSO there was little change during the first 5 hr and then a gradual return to normal values by 24 hrs. The major fall in the SER after removal of the drugs occurred as the cellular thiols increased to 60% of control values.


Sensitivity to topically applied vitamin E.
A search of the literature has not revealed any reports of allergic eczematous contact dermatitis due to the topical application of vitamin E. A case of contact allergy to synthetically produced alpha-tocopherol is herein reported. It is felt that this is a rare event in view of the fact that this vitamin is widely used topically in this country and abroad.


Improving the texture properties and protein thermal stability of Antarctic krill (Euphausia superba) by L-lysine marination.
The quality deterioration of Antarctic krill (Euphausia superba) after thermal processing limits its industrial application. This study sought to improve the texture characteristics of Antarctic krill after heat treatment through pre-soaking using l-lysine (Lys) solution and sodium tripolyphosphate (STPP). Moreover, the effects of Lys on heat-treated Antarctic krill were explored. Lys significantly reduced the cooking loss and improved the texture characteristics of Antarctic krill during heat treatment. The low-field nuclear magnetic resonance results showed that Lys reduced the water loss of Antarctic krill during heat treatment. Additionally, the surface hydrophobicity, Fourier transform infrared spectroscopy, and endogenous fluorescence spectroscopy results showed that Lys could inhibit the structural damage of Antarctic krill protein under the thermal denaturation condition and enhance the thermal stability of the protein. The scanning electron microscopy results showed that Lys could protect the structural integrity of Antarctic krill muscle fibers during heat treatment. The cooking loss in the Lys added groups was better than the sodium tripolyphosphate added group, and 2.0% Lys solution could minimize the cooking loss of Antarctic krill. The secondary and tertiary structures of the Antarctic krill protein were actively protected by Lys during heat treatment. Overall, the study will provide insights into the application of Lys in the food industry as a natural additive and an alternative to phosphate. © 2021 Society of Chemical Industry.


Applying circular posterior-hinged craniotomy to malignant cerebral edemas.
Malignant brain edemas are often fatal, regardless of whether they are treated conservatively with sedation, blood pressure management, mannitol-therapy, hyperventilation and hypothermia, or non-conservatively with routine trepanation. Unfortunately, temporal trepanation may result in significant brain damage through herniation of the cerebrum at the edges of the trepanation openings. In one case of a 26-year-old male with severe head injury, a circular posterior-hinged craniotomy (CPHC) was performed after an ineffective unitemporal trepanation for evacuation of an acute subdural hematoma. This ultimately successful operation prompted experimental and morphologic investigations on a new surgical procedure for lowering intracranial pressure (ICP). In 12 of 15 human cadavers, an experimentally ICP was lowered by a CPHC with between 9-21 mm of frontal elevation of the calvaria. Using computer simulation, the frontal elevations of the calvaria were "virtually" performed on 3D reconstructions from CT scans of skulls, and the intracranial volume gained was measured with a computer software program. The volume increase of the cranial cavity showed a relatively constant relation to the cranial capacity and was increased by 6.0% (+/-0.4%) or 78 cm(3) with a 10 mm elevation and by 12.4% (+/-0.7%) or 160 cm(3) with a 20 mm elevation. There were no significant differences with skulls of different ages or ethnic origin; however, a significant effect of gender (F = 7.074; P < or = 0.013) on the gained volume in percent of the cranial capacity for the 20 mm elevation was observed. This difference can be explained by the inverse relationship between volume increase and cranial capacity (r = -0.507; P < or = 0.004).


Exercise counselling by family physicians in Canada.
Exercise counselling is not frequently conducted by family physicians in several countries. Little is known about the exercise counselling practices of family physicians in Canada. The objective of this study was to assess physician confidence, current versus desired practice, and barriers related to the counselling of exercise by family physicians in Canada. The study was a cross-sectional survey that included a random selection of family physicians in six provinces. A total of 330 family physicians completed the questionnaire, resulting in a response rate of 61.1%. A family physician was defined as a physician who practices family medicine at least 75% of their practice time. A total of 58.2% believed only 0-25% of their patients would respond to their counselling and 42.4% felt "moderately knowledgeable" to exercise counsel. Only 11.8% counselled 76-100% of their patients about exercise, but 43.3% thought they should be counselling 76-100% of their patients. Barriers to exercise counselling that rated most important included lack of time (65.7%) and lack of exercise education in medical school (64.8%). Family physicians indicated their current level of exercise counselling is suboptimal and confidence levels in exercise counselling were not high. Future educational opportunities for physicians may assist in improving exercise counselling.


pH-labile artificial natural killer cells for overcoming tumor drug resistance.
Natural killer (NK) cells exert cytotoxic effects against infected or stressed cells, such as tumor cells, without the limitation of major histocompatibility complex (MHC) I. NK cells secrete perforins to form tunnels to mediate the entry of granzyme into target cells. This strategy, selected by natural evolution, provides a feasible method for the delivery of antitumor drugs against intracellular targets, and avoids drug-resistant mechanisms in tumor cells, such as the pumping out of drugs mediated by multidrug resistance. We constructed pH-labile artificial NK cells (ANKC) based on nature to mediate high levels of drugs in tumor cells to overcome tumor drug resistance. Mesoporous silicon nanoparticles (MSNs) modified with benzaldehyde were designed to function as scaffolds for ANKC. Doxorubicin (Dox), a model antitumor drug, was loaded into the pores of MSNs. Melittin, a pore-forming peptide, was utilized as the gate for mesopores with an acid-labile Schiff base linkage. pH-labile ANKC released melittin and Dox in slightly acidic tumor microenvironments. Melittin, like perforin, assembled tunnels on the plasma membrane or endosome, ensuring the intracellular transportation of Dox. Dox, similar to granzyme, induced the apoptosis of tumor cells. The combinational treatment partially eased the drug resistance mechanism, such as pumping out of drugs, by continuous intracellular drug accumulation mediated by melittin pores. The pH-labile ANKC demonstrated significant Dox enrichment in drug-resistant MCF-7/Adr cells and MCF-7/Adr-based xenograft tumors in a mouse model, which eventually contributed to efficient inhibition of the proliferation and growth of MCF-7/Adr tumors. PH-labile ANKC provided a potential strategy to treat drug-resistant tumors.


Melatonin (MEL) and its use in neurological diseases and insomnia: Recommendations of the French Medical and Research Sleep Society (SFRMS).
The French Medicine and Research Sleep Society had organized a consensus conference about sleep/wake circadian rhythms and their disorders. During this conference a subgroup of 11 sleep doctors/researchers looked specifically at the use of MEL in different pathologies. This article gives a summary of the main results of MEL therapy in some neurological diseases and insomnia approved by this consensus group. Exogenous MEL, which crosses the blood-brain barrier, has been used as a treatment in its two available forms: an immediate release form that principally shows a chronobiotic action and a long release form that mimics the physiological MEL secretion rhythm and is used to replace reduced physiological secretion. MEL secretion decreases frequently with age, mostly in elderly insomniacs and dementia patients. Results of level A studies show that MEL therapy, used as an add-on treatment, has beneficial effects in mild cognitive impairment (MCI) and Alzheimer patients with sleep disorders in improving sleep quality and in regulating the sleep/wake rhythm. MEL has to be prescribed as early as possible and for a long period, at a dose of 2 to 5 or 10 mg. It may have a beneficial effect on cognitive function in MCI but shows no effect in moderate to severe Alzheimer's disease. It should be emphasized that there are no serious side effects with MEL treatment. In these diseases, light therapy used 12 hours before melatonin treatment has a positive synergic effect. In REM sleep behavior disorder, immediate release MEL should be prescribed first as its side effect profile is much better than clonazepam shortly before bedtime. MEL has a good efficacy on clinical symptoms and PSG REM sleep without atonia episodes and is well tolerated. In Parkinson disease with sleep disorders and without REM sleep behavior disorder, MEL seems to improve subjective sleep quality but no conclusions can be drawn. There is insufficient scientific proof for using MEL as a prophylactic treatment in primary headache, migraine and cluster headache. In epileptic patients, MEL can be safely used to regulate the sleep/wake rhythm and to improve insomnia but more randomized controlled studies are necessary. In primary or no-comorbid insomnia, only a 2 mg dose of slow release MEL, 1 to 2 hours before bedtime, over a period of 3 to 12 weeks, is recommended. It decreases sleep onset latency, improves quality of sleep, morning alertness and quality of life without serious side effects and without withdrawal symptoms.


Galectin-3 expression in papillary microcarcinoma of the thyroid.
Galectin-3 is a beta-galactoside binding protein, recently recognized as a promising molecular marker of thyroid malignancy. As reported in several studies, galectin-3 is highly expressed in papillary thyroid carcinoma, but its expression has not been investigated in papillary microcarcinoma, which is a variant of papillary thyroid carcinoma. Using a monoclonal antibody to galectin-3 and the avidin-biotin-peroxidase complex (ABC) immunohistochemical technique, we analysed galectin-3 expression in 63 cases of papillary microcarcinoma. The results showed immunohistochemical reactivity for galectin-3 in 51 (80.9%) cases. Intensity of staining varied from strong or moderate to weak. Galectin-3 localization was mostly cytoplasmic, but also membranous or nuclear in some cells. Immunohistochemical expression of galectin-3 was not found in 12 (19.1%) cases. Most galectin-3 negative microcarcinomas (10/12) were of the non-classical type, i.e. without papillary architecture. Neither the frequency nor the intensity of a positive reaction was related to tumour size. Galectin-3 gene is expressed at the protein level in most papillary microcarcinomas, although with slightly lower frequency than that reported for clinically evident papillary thyroid carcinoma. The presence of galectin-3 in clinically silent microcarcinomas may indicate that galectin-3 is not related to growth or aggressiveness of papillary thyroid microcarcinomas but rather plays some other role in thyroid tumour biology.


Influence of simultaneous targeting of the bone morphogenetic protein pathway and RANK/RANKL axis in osteolytic prostate cancer lesion in bone.
Metastasis to bone is the leading cause of morbidity and mortality in advanced prostate cancer patients. Considering the complex reciprocal interactions between the tumor cells and the bone microenvironment, there is increasing interest in developing combination therapies targeting both the tumor growth and the bone microenvironment. In this study, we investigated the effect of simultaneous blockade of BMP pathway and RANK/RANKL axis in an osteolytic prostate cancer lesion in bone. We used a retroviral vector encoding noggin (RetroNoggin) to antagonize the effect of BMPs and RANK:Fc, which is a recombinant RANKL antagonist was used to inhibit RANK/RANKL axis. The tumor growth and bone loss were evaluated using plain radiographs, hind limb tumor measurements, micro PET/CT ((18)FDG and (18)F-fluoride tracer), and histology. Tibias implanted with PC-3 cells developed pure osteolytic lesions at 2-weeks with progressive increase in cortical bone destruction at successive time points. Tibias implanted with PC-3 cells over expressing noggin (RetroNoggin) resulted in reduced tumor size and decreased bone loss compared to the implanted tibias in untreated control animals. RANK:Fc administration inhibited the formation of osteoclasts, delayed the development of osteolytic lesions, decreased bone loss and reduced tumor size in tibias implanted with PC-3 cells. The combination therapy with RANK:Fc and noggin over expression effectively delayed the radiographic development of osteolytic lesions, and decreased the bone loss and tumor burden compared to implanted tibias treated with noggin over expression alone. Furthermore, the animals treated with the combination strategy exhibited decreased bone loss (micro CT) and lower tumor burden (FDG micro PET) compared to animals treated with RANK:Fc alone. Combined blockade of RANK/RANKL axis and BMP pathway resulted in reduced tumor burden and decreased bone loss compared to inhibition of either individual pathway alone in osteolytic prostate cancer lesion in bone. These results suggest that simultaneous targeting of tumor cells and osteoclasts may be the most effective method of inhibiting the progression of established osteolytic metastatic lesions in vivo.


Effect of affective temperament on illness characteristics of subjects with bipolar disorder and major depressive disorder.
Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder (BD) or major depressive disorder (MDD) has been described. However, the strength of such relationship should be tested while considering other factors influencing the diagnosis of BD/MDD. Literature also lacks a comprehensive description of the interplay between affective temperament and characteristics of mood disorders. The aim of the present study is to address these issues. This is a multicentric observational study including 7 Italian university sites. Five-hundred-fifty-five euthymic subjects with BD/MDD were enrolled and further divided in those with hyperthymic (Hyper, N = 143), cyclothymic (Cyclo, N = 133), irritable (Irr, N = 49), dysthymic (Dysth, N = 155), and anxious (Anx N = 76) temperaments. Linear, binary, ordinal and logistic regressions were performed to assess the association between affective temperaments and i) diagnosis of BD/MDD; ii) characteristics of illness severity and course. Hyper, Cyclo and Irr were more likely to be associated with BD, together with earlier age of onset and presence of a first-degree relative with BD. Anx and Dysth were more associated with MDD. Differences in association between affective temperaments and characteristics of BD/MDD were observed for hospital admissions, phase-related psychotic symptoms, length and type of depression, comorbidity and pharmacological intake. Small sample size, cross-sectional design, recall biases. Specific affective temperaments were associated to certain characteristics of illness severity and course of BD or MDD. Evaluation of affective temperaments might help a deeper understanding of mood disorders.


Protocol to prepare phenanthrenequinone moieties-rich carbon materials through electrochemical oxidation.
The electrocatalytic behavior of carbon materials is related to the oxygen-containing groups, in that the type of groups determines the activity of carbon materials. Among them, phenanthrenequinone (PQ) moieties functionalized carbon materials are critical species in the catalysis field. Here, we prepare PQ moieties functionalized carbon materials through electrochemical oxidation. We provide the synthesis details of the PQ groups, an approach for the detection of PQ groups, and a performance evaluation for electrocatalytic oxygen evolution reaction (OER) under acidic conditions. For complete details on the use and execution of this protocol, please refer to Lu et al. (2022b).


Activation of Cytotoxic Natural Killer Cells After Aneurysmal Subarachnoid Hemorrhage.
Cell-mediated inflammation is critical in the development of cerebrovascular complications after aneurysmal subarachnoid hemorrhage. We analyzed the course for activated CD16brightCD56dim cytotoxic natural killer (NK) cells in cerebrospinal fluid of 15 patients. Patients were classified by occurrence of cerebral vasospasm (CV) and delayed cerebral ischemia. NK were monitored by flow cytometry between day 1 and 14 after hemorrhage. Twelve patients (80%) developed CV with a mean day of detection at 3.9 ± 1.6. In those patients, cell count for NK increased from 1.40 ± 1.42 cells/μL on day 1 to a peak of 11.66 ± 11.56 cells/μL on day 6.1 ± 2.9 (P = 0.001). An increase of mean cerebral blood flow velocity in transcranial Doppler from 71.33 ± 12.93 cm/second to 166.20 ± 20.19 cm/second (P < 0.01) and an increase in number of vascular axes affected by CV was detected (P < 0.01). In patients with grade 3 CV (n = 4, 33.3%), activated NK counts were significantly higher than in patients who did not have CV (23.18 ± 13.92 cells/μL vs. 0.02 ± 0.01 cells/μL; P = 0.029). NK counts were significantly different between patients with grade 1 and grade 3 CV (P = 0.04). Patients who did not have CV who showed low NK counts achieved better functional outcome (Glasgow Outcome Scale [GOS] score, 4.6 ± 0.6) at discharge than did patients with CV grade 2 (GOS score, 3.3 ± 0.5) and CV grade 3 (GOS score, 2.3 ± 0.5) who showed increased NK cell counts (CV grade 0 vs. CV grade 2, P = 0.048; CV grade 0 vs. CV grade 3, P = 0.001). Activated CD16brightCD56dim cytotoxic NKCSF cell counts showed a mean maximum (14.15 ± 12.21 cells/μL) when delayed cerebral ischemia occurred. The increase of activated CD16brightCD56dim cytotoxic NK cells in cerebrospinal fluid after aneurysmal subarachnoid hemorrhage suggests an increased risk of CV and delayed cerebral ischemia.


First Trimester Listeria monocytogenes Septicemia.
Little is known about fetal outcome after Listeria monocytogenes septicemia in the first trimester of pregnancy. A primigravida with L. monocytogenes septicemia at 9 weeks gestation was treated with amoxicillin. At 40 weeks gestation a healthy female infant was born. This case shows that fetal outcome can be normal after appropriate treatment of maternal L. monocytogenes septicemia during embryogenesis.


Effect of mouse interferon on retrovirus production by chronically infected rat cells.
Mouse interferon (IFN) inhibited retrovirus release by both mouse and rat cells with the same efficiency. However, the antiviral state developed more slowly in rat than in mouse cells, and after removal of IFN it also persisted for a longer time in rat than in mouse cells. Under conditions where IFN strongly inhibited virus production it had no effect on cell replication nor on cellular RNA or protein synthesis.


Colon perforation in an adolescent after short-term diclofenac intake.
Chronic intake of non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to cause side-effects distal to the duodenum. These include strictures, diaphragm-like lesions and perforations of the small and large intestines. This is the first case report on colon perforation occurring in an adolescent (16-year-old girl) after short-term diclofenac intake.


Use and outcomes of a cholesterol-lowering intervention for rural elderly subjects.
Few studies have evaluated the efficacy of cholesterol-lowering interventions in a community setting and have included a control or comparison group. As part of a preventive health demonstration project in rural Pennsylvania, Medicare beneficiaries underwent cholesterol screening to identify high-risk individuals with serum cholesterol levels > or = 240 mg/dL. These high-risk individuals were randomized to a cholesterol-lowering intervention through either local hospitals or physicians' offices or to a control group. Baseline and follow-up serum cholesterol levels collected two to three years later were compared according to service location (hospital versus physician's office), intervention attendance, degree of participation, baseline heart disease history, and cholesterol-lowering medication use at follow-up. Serum cholesterol levels decreased between 5.7% and 6.6% in the hospital-based and physician-based groups, as well as in a control group not offered the intervention. Participation rates did not differ between treatment groups, nor did participation affect serum cholesterol levels. Attendance level and heart disease history were not associated with a greater decrease in serum cholesterol levels. Individuals reporting cholesterol-lowering drug use at follow-up had significantly higher baseline serum cholesterol levels and a significantly greater decrease in total serum cholesterol (P < .0001) than those not on medication. Both nonpharmacological (diet) and pharmacological (drug) interventions will reduce serum cholesterol levels and heart attack risk. The study results suggest that, at least for older individuals, the impact of nonpharmacological interventions on the community is minimal. We conclude that only very aggressive treatment will significantly loser serum cholesterol levels in older individuals at risk for heart attack.


Changes in the epidemiology of gastroenteritis in a paediatric short stay unit following the introduction of rotavirus immunisation.
Acute gastroenteritis (AGE) has been a significant component of the clinical load in the short stay unit (SSU) at the Royal Children's Hospital (RCH) since its establishment in 2004. Since the introduction of routine rotavirus immunisation in Australia in 2007 there has been a clinical impression of a substantial reduction in AGE managed in the SSU. This study aimed to examine changes in the epidemiology of AGE in the SSU, and RCH overall, between 2005 and 2009 and explore whether this reflects a change specifically in AGE due to rotavirus. Discharge coding data for AGE from all inpatient wards, the SSU and emergency department (ED) at the RCH were examined. Stool virology results for the same period were analysed. Since 2007 there has been a 58% reduction in AGE admissions to the SSU. The median age of patients admitted to the RCH with rotaviral enteritis has increased from 1.3 years to 3.8 years. Presentations to the ED for AGE have fallen from 53 to 34 cases per 1000 attendances between 2004 and 2009, and admission rates from the ED have fallen from 23 to 13% of AGE presentations. Detection rates of rotavirus fell from 13.1 to 6.7% between 2005 and 2009. A marked decrease in AGE-related clinical activity and reduction in rotavirus detection at the RCH has occurred since the introduction of routine rotavirus immunisation in Australia. This has significant resource planning implications for units based on short stay models of care.


lncRNA SNHG4 promotes cell proliferation, migration, invasion and the epithelial-mesenchymal transition process via sponging miR-204-5p in gastric cancer.
Long non‑coding (lnc)RNAs and microRNAs (miRNAs/miRs) have physiological and pathological functions in various diseases, including gastric cancer (GC). The current study explored the association between lncRNA small nucleolar RNA host gene 4 (SNHG4) and miR‑148a‑3p, and their functions in GC cells. SNHG4 expression and overall survival data were analyzed using bioinformatics, and the interaction of SNHG4 and miR‑148a‑3p was predicted using starBase and confirmed via a dual‑luciferase reporter assay. Cell viability, colony formation ability and apoptosis rate were detected using Cell Counting Kit‑8, colony formation and flow cytometry assays, respectively. Cell migration and invasion were determined via wound‑healing and Transwell assays. mRNA and protein expression levels were determined via reverse transcription‑quantitative PCR and western blotting. The results demonstrated that in GC tissues and cell lines, SNHG4 was highly expressed, while miR‑204‑5p expression was decreased, and that the expression levels of SNHG4 and miR‑204‑5p were negatively correlated. The downregulated expression of SNHG4 decreased the effects of miR‑204‑5p inhibitor on promoting cell proliferation, migration, invasion and epithelial‑mesenchymal transition, but enhanced the inhibitory effect of miR‑204‑5p on GC cell apoptosis. The findings of the current study revealed the potential mechanism of the SNHG4‑miR‑204‑5p pathway in GC, which may be conducive to the development of novel drugs against GC growth.


Synthesis of some quinazolinones inspired from the natural alkaloid L-norephedrine as EGFR inhibitors and radiosensitizers.
A set of quinazolinones synthesized by the aid of L-norephedrine was assembled to generate novel analogues as potential anticancer and radiosensitizing agents. The new compounds were evaluated for their cytotoxic activity against MDA-MB-231, MCF-7, HepG-2, HCT-116 cancer cell lines and EGFR inhibitory activity. The most active compounds 5 and 6 were screened against MCF-10A normal cell line and displayed lower toxic effects. They proved their relative safety with high selectivity towards MDA-MB-231 breast cancer cell line. Measurement of the radiosensitizing activity for 5 and 6 revealed that they could sensitize the tumour cells after being exposed to a single dose of 8 Gy gamma radiation. Compound 5 was able to induce apoptosis and arrest the cell cycle at the G2-M phase. Molecular docking of 5 and 6 in the active site of EGFR was performed to gain insight into the binding interactions with the key amino acids.


Systematic Sonography Looking for Occult Wounds: accuracy of an abdominal ultrasound adjunct in penetrating trauma.
Systematic Sonography Looking for Occult Wounds (SSLOW) in trauma is a novel technique for the evaluation of intra-abdominal wounds in penetrating trauma. No data exist regarding the effectiveness. The objective of this study was to evaluate the accuracy of the SSLOW exam. This is a prospective collected case series conducted over a period of 10 months and took place at the Accident and Emergency Department (A&E) of the Georgetown Public Hospital Corporation (GPHC). The study enrolled patients presenting to the A&E who were 16 years old or greater with penetrating abdominal trauma. All patients with penetrating trauma received an E-FAST examination. If the E-FAST examination was negative, a SSLOW examination was completed. The sonographer evaluated for free fluid collection between the loops of bowel. The results of the SSLOW were compared to usual care (surgery consult, serial abdominal and E-FAST exams, laparotomy, and 7-day follow-up) and then categorized into four groups: true positive, false positive, true negative, and false negative. These results lead to four categorical values. From these results, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios were calculated. There were 5 (12%) true positives, 1 (2%) false positive, 37 (86%) true negatives, and zero (0%) false negative. The SSLOW was 100% sensitive (95% CI 5-100%) and 97% specificity (95% CI 74-96%). There was an 80% positive predictive value (95% CI 1.0-64% 95% CI) and 100% negative predictive value (95% CI 88-100%). The positive likelihood ratio was 8.4 (95% CI 3.69-19.1) and negative likelihood ratio was 0. The SSLOW examination may be a useful tool in the evaluation of penetrating abdominal injuries.


The 5-HT4 receptor subtype inhibits K+ current in colliculi neurones via activation of a cyclic AMP-dependent protein kinase.
1. The aim of the present study was to examine the effect of 5-hydroxytryptamine (5-HT) on K+ current in primary culture of mouse colliculi neurones and to identify the 5-HT receptor subtype that could be involved in this effect. 2. The voltage-activated K+ current of the neurones was partially blocked by 8-bromo adenosine 3':5'-cyclic monophosphate (8-bromo-cyclic AMP). This effect was mimicked by 5-HT and the action of 5-HT could be antagonized by H7, a non specific protein kinase inhibitor, and by PKI, the specific cyclic AMP-dependent protein kinase blocker. 3. A similar cyclic AMP-dependent blockade of the K+ current was found with renzapride (BRL 24,924) and other 5-HT4 receptor agonists such as cisapride, BIMU 8, zacopride and 5-methoxytryptamine (5-MeOT). ICS 205,930, the classical 5-HT4 receptor blocker, could not be used in this study because it inhibited the studied K+ current by itself. However, the novel 5-HT4 receptor antagonist, DAU 6285 blocked the effects of 5-HT and renzapride on the K+ current. 4. The current was insensitive to the 5-HT1 and 5-HT3 receptor agonists (8-hydroxy-2-(di-n-propylamino) tetralin, RU 24,969, carboxamidotryptamine, 2-CH3-5-HT) as well as to 5-HT1, 5-HT2 and 5-HT3 antagonists (methiothepin, ketanserin, ondansetron [GR 38,032]). Moreover, these antagonists did not affect the actions of the tested 5-HT4 receptor agonists. 5. The present results show that part of the voltage-activated K+ current in mouse colliculi neurones is cyclic AMP-sensitive and the blockade of the current by 5-HT involves the 5-HT4 receptor subtype.The putative implication of 5-HT4 receptors in neuronal plasticity, via a blockade of K+ channels, is discussed.


Ammonia volatilization and the effects of large grazing mammals on nutrient loss from East African grasslands.
Ammonia volatilization losses measured from soils at seven sites in the Serengeti National Park, Tanzania during the 1986 growing season ranged from 2.78±0.49% to 25.03±1.34% of nitrogen applied. Although peak ammonia losses ranged from 0.071±0.018 to 0.404±0.040 g N m-2 h-1, rates dropped to zero within four days, and calculations reveal that volatilization losses represent minor fluxes in the context of the system's nitrogen cycling. Volatilization losses were inversely correlated with grazing intensity experienced by a site, and it appears that large ungulates themselves contribute to nutrient conservation throught indirect interactive effects on system processes.


An innovative analysis of nasolabial dynamics of surgically managed adult patients with unilateral cleft lip and palate using 3D facial motion capture.
To compare dynamic nasolabial movement between end-of-treatment cleft and a matched non-cleft group in adult patients. Thirteen treated adult participants with unilateral cleft lip and palate had images taken using a facial motion capture system performing a maximum smile. Seventeen landmarks were automatically tracked. For each landmark pair, on either side of the midline, changes in the x, y, and z directions were used to analyze the magnitude of displacement and path of motion. An asymmetry score was developed at rest, mid-smile, and maximum smile to assess the shape of the mouth and/or nose. At maximum smile, displacement of right and left cheilion was clinically and statistically (p < 0.05) less in the cleft group. The lip asymmetry score was greater (p < 0.05) at each time point in the cleft group using the clinical midline. Using Procrustes superimposition, the differences were significant (p < 0.05) only at rest and mid-smile. The alar bases were displaced significantly less (p < 0.05) in the z direction in the cleft group. The asymmetry score of the alar base was significantly higher using the clinical midline than using Procrustes superimposition in patients with cleft conditions (p < 0.001). In the cleft group, at maximum smile, the right and left cristae philter moved significantly less (p < 0.05) in the x and z directions. There was an increase in asymmetry score of the corners of the mouth and alar bases from rest to maximum smile. The lips were similar in shape but oriented differently in the faces of patients with cleft conditions than in individuals without those conditions.


Fish oil supplementation attenuates myointimal proliferation of the abdominal aorta after balloon injury in diet-induced hypercholesterolemic rabbits.
The effects of supplementing with fish oil on the myointimal proliferation of the abdominal aorta after balloon injury were studied in control and in rabbits fed a 1% cholesterol-enriched diet, with and without 10% fish oil supplementation. Twenty-one animals in each group underwent a balloon injury of the abdominal aorta and left common iliac artery after 2 weeks of feeding. The animals remained on their respective diets thereafter. In 7 balloon-injured and 7 sham-operated animals of each group, the abdominal aorta was harvested 3 days later for the analysis of prostanoids, malondialdehyde, superoxide dismutase activity, [3H]thymidine uptake, and cholesterol levels. In the other 7 balloon-injured rabbits of each group, the tissue was harvested 3 weeks later for morphometric study. The fish oil-treated rabbits had the lowest aortic production of thromboxane B2 levels and the highest 6-keto-PGF1 alpha/thromboxane B2 ratios among the three groups after balloon injury. The aortic malondialdehyde levels of the cholesterol-fed rabbits were significantly higher than the other two groups (each P < 0.001) independent of balloon injury. The myointimal proliferation of the abdominal aorta and left common iliac artery in the fish oil-treated rabbits was less severe than in the cholesterol-fed animals (both P < 0.001) and was comparable with the controls. These results suggest that a fish oil supplement changes prostanoid metabolism to a favorable pattern and reduces lipid peroxidation on the abdominal aortic wall, thus attenuating myointimal proliferation after balloon injury in diet-induced hypercholesterolemic rabbits.


A study of the interhemispheric correlation during sleep in elderly subjects.
The interhemispheric relationship during sleep in elderly subjects was studied throughout the night by a minute-by-minute computation of two linear correlation coefficients between right and left EEG activities. One of these coefficients (X delta) related to the 1-4-Hz band activity, and the other (X sigma) to the 12.5-14.5-Hz band activity. For five of the six subjects examined, it was found that the rapid-eye-movement (REM) mean values of both coefficients were significantly different from the nonrapid-eye-movement (NREM) values. A comparison between this elderly group and a control group of young subjects, examined previously, did not reveal any significant shift, either for the REM or for the NREM mean values of the coefficients.


Metabolic syndrome and the risk of severe cancer events: a longitudinal study in Japanese workers.
Metabolic syndrome (MetS) is associated with cancer risk; however, little is known regarding its relationship with the risk of cancer-related premature death and long-term sick leave (LTSL), which can lead to a substantial loss in working years. The present study aimed to quantify the all-site and site-specific associations between MetS and the risk of severe cancer events (a composite outcome of LTSL and mortality due to cancer) in a large working population in Japan. We recruited 70,875 workers (59,950 men and 10,925 women), aged 20-59 years, who attended health check-ups in 2011 (10 companies) and 2014 (2 companies). All workers underwent follow up for severe cancer events until March 31, 2020. MetS was defined in accordance with the Joint Interim Statement. Cox regression models were used to quantify the association between baseline MetS and severe cancer events. During 427,379 person-years of follow-up, 523 participants experienced the outcome consisting of 493 LTSLs of which 124 eventually resulted in death, and 30 deaths without taking LTSL. The adjusted hazard ratios (HR) (95% confidence intervals [CI]) for composite severe events due to all-site, obesity-related, and non-obesity-related cancer among those with vs. without MetS were 1.26 (1.03, 1.55), 1.37 (1.04, 1.82), and 1.15 (0.84, 1.56), respectively. In cancer site-specific analyses, MetS was associated with an increased risk of severe events due to pancreatic cancer (HR, 2.06; 95% CI, 0.99-4.26). When mortality was treated solely as the endpoint, the association was significant for all-site (HR, 1.58; 95% CI, 1.10-2.26), and obesity-related (HR, 1.59; 95% CI, 1.00-2.54) cancer. Additionally, a greater number of MetS components was associated with a greater risk of both severe cancer events and cancer-related mortality (P trend < 0.05). Among Japanese workers, MetS was associated with an increased risk of severe cancer events, especially those due to obesity-linked cancer.


Bacterial endophthalmitis associated with exposed monofilament sutures following corneal transplantation.
Three cases of bacterial endophthalmitis following corneal transplantation resulted from suture abscesses that were initiated by loose or broken exposed sutures. Histopathologic examination clearly demonstrated that the infection gained access to the anterior chamber by following a deeply placed suture that traversed the posterior wound gap at the donor-host interface. We believe that exposed sutures may lead to significant postoperative complications and must be carefully observed.


Early MOnitoring of REsponse (MORE) to Golimumab Therapy: Results of a Multicentre, Prospective Observational Trial.
The therapeutic goal of clinical remission in patients with moderate to severe ulcerative colitis (UC) is achieved after biological therapy only in 16-39%. Individualization of therapeutic intervention would benefit from prediction of early response. The primary objective of our study was to assess golimumab (GLM) trough serum level of ≥2.5 μg/mL in combination with a reduction of faecal calprotectin (FC) of ≥50% at week 6 compared to baseline to predict clinical response at week 26 after regular GLM intake. Patients with moderate to severe active UC and planned GLM treatment were recruited for a prospective, multicentre, observational study in Germany. Prediction of clinical response was assessed by FC and GLM trough level. Missing data were imputed as therapy failure according to the last observation carried forward method. Fifty nine patients have been enrolled. 54% of patients were anti-TNF naïve. Clinical response at week 6 was a significant predictor for achieving clinical response at week 26 (odds ratio [OR] 10.97, confidence interval [CI], 2.96-40.68; p < 0.001). Moreover, patients with a GLM trough level of ≥2.5 μg/mL and a ≥50% reduction of FC at week 6 had an OR of 5.33 (95% CI, 0.59-47.84) to achieve clinical response at week 26. Clinical response at week 6 is the best predictive marker for achieving clinical response at week 26. Consideration of significant reduction of FC and trough GLM serum levels could improve prediction of response.


Zero valent iron mediated degradation of the pharmaceutical diazepam.
Parameters that influence the zero valent iron mediated degradation of the pharmaceutical diazepam (DZP) were evaluated including the iron concentration and its pre-treatment, the effect of complexation with EDTA and oxic versus anoxic condition. It was observed that acid pre-treatment of iron particles is important for degradation efficiency and that H(2)SO(4) is a better choice than HCl, resulting in higher degradation of DZP. Under oxic conditions, the degradation of DZP achieved 96% after 60 min using Fe(0) (25 g L(-1)) pre-treated with H(2)SO(4) in the presence of EDTA (119 mg L(-1)), while mineralization achieved around 60% after the same time. Under anoxic conditions, degradation occurred, however at lower extent, achieving 67% after 120 min. The addition of EDTA improved the treatment efficiency in 20% leading to 99% DZP degradation after 120 min. The first intermediates formed during DZP degradation were identified using LC/MS analysis and revealed the formation of mono- and di-hydroxylated products from DZP during Fe(0)/EDTA/O(2) degradation, which evidences that (·)OH was the main oxidizing species formed in this process.


Students' rights in a public institution.
This article describes the differences in public and private institutions, and how faculty knowing the differences can determine the rights to which students are entitled. It further provides cases to demonstrate the rights that nursing students have in a public institution.


Predictive factors for achieving low disease activity at 52 weeks after switching from tumor necrosis factor inhibitors to abatacept: results from a multicenter observational cohort study of Japanese patients.
This study aimed to identify predictive factors for achieving low disease activity (LDA) in rheumatoid arthritis (RA) patients switching from tumor necrosis factor inhibitors (TNFis) to abatacept (ABT). Patients who were registered in the multicenter observational Tsurumai Biologics Communication Registry (TBCR) were enrolled in this study. Predictive factors for LDA achievement at each time point were determined by univariate and multivariate logistic regression analyses. The cutoffs of 28-point count Disease Activity Score (DAS28)-C-reactive protein (CRP) and ΔDAS28-CRP from baseline up to 24 weeks for LDA achievement at 52 weeks were explored using receiver operating characteristic (ROC) curves. Of 2771 RA patients registered until 2013, 76 with moderate or high disease activity were selected. Twenty-six percent of the patients achieved LDA. Multivariate analysis confirmed that DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks were independent factors for LDA achievement at 52 weeks [odds ratio (OR) 0.26, 95% confident interval (CI) (0.12-0.56), OR 0.25, 95% CI (0.11-0.57), respectively]. The best cutoff values of DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks for LDA at 52 weeks were 3.9 (sensitivity 0.85, specificity 0.78) and -0.97 (sensitivity 0.70, specificity 0.70), respectively. Seventy-one percent of patients who achieved both of these cutoff values at 12 weeks achieved LDA at 52 weeks. Our findings suggest that the clinical course up to 12 weeks is important for predicting long-term outcomes when switching from TNFis to ABT.


Seven tumor markers in benign and malignant germ cell tumors of the ovary.
Seven tumor markers were analyzed clinically in 135 patients with germ cell tumors of the ovary who were treated in Tokai Ovarian Tumor Study Group, an association comprising Nagoya University and its affiliated hospitals, between January 1979 and September 1990. Positive rate of AFP was 100% (36/36) in yolk sac tumor, 61.9% (13/21) in immature teratoma, and 11.8% (2/17) in dysgerminoma, but there were no positive cases of mature cystic teratoma with malignant transformation (0/7) and mature cystic teratoma (0/31). Positive rate of CA125 was over 50% in all tumor types except mature cystic teratoma, which showed a positive rate of 23.7%. CA125 was useful for the screening of malignant germ cell tumors. CA19-9 showed a high positive rate in teratomatous tumors, which were immature teratoma, mature cystic teratoma with malignant transformation, and mature cystic teratoma. Dysgerminoma and yolk sac tumor, especially dysgerminoma, had a high positive rate of LDH. TPA and CEA were not considered useful tumor markers for germ cell tumors of the ovary.


Erratum: Corrigendum: Beating the thermodynamic limit with photo-activation of n-doping in organic semiconductors.
Nature Materials 16, 1209-1215 (2017); published online 13 November 2017; corrected after print 15 December 2017. In the version of this Article originally published, the source of 'ZADN' stated in the Methods should have read 'obtained as free research samples from Guangzhou ChinaRay OptoelectronicMaterials' instead of 'China-Ray'.


Adoption of measures by psychiatric hospitals to prevent SARS-CoV-2.
This article analyzes the scientific evidence on the measures adopted by psychiatric hospitals to prevent COVID-19 contamination among hospitalized people. It refers to a literature review in the MEDLINE/PUBMED, Web of Science, and EMBASE databases. There was the incorporation of studies describing measures used to prevent the spread of COVID-19 among patients admitted to psychiatric institutions. The research articles that evaluated patients in partial follow-up at health facilities were excluded. Between 13 selected studies, two thematic categories were established: Measures adopted to reduce the transmission of COVID-19 in the admission of psychiatric patients; Measures adopted to reduce the transmission of COVID-19 during hospitalization of psychiatric patients. There are similarities and differences in the measures adopted by psychiatric hospitals. It was noted that admission and isolation policy for 14 days was a consensus. However, the testing method for screening Sars-CoV-2 differs between the realities. Concerning hospitalization, there is a similarity in the use of technologies in the care of psychiatric patients. In contrast, there is no standardization in the measures taken since, due to their structure; psychiatric hospitals have restrictions on the adoption of distance rules.


[Complications of cardiac catheterisation in congenital heart disease. 30 years of experience. A new risk-adjusted score].
To present a risk-ajusted score of complications during cardias catheterization in congenital heart disease. observational, analitic, ambispective of 3.504 cases. The data analyzed included age, heart disease, type of procedure, major and minor complications. 3.504 procedures performed between october 1987 and may 2019. The variables were age, heart disease, procedere and clinical stege. Each patients was categorized as low risk 5 to 7 points, moderate risk 8 to 11 points and higt risk 12 to 22 points. The score was validated using the Hosmer-Lemeshow test and the ROC curve (Receiver Operating Characteristic). complications 177 (5%) 66 major (1.9%) and 111 minor (3.1%). Mortality was 0.4% (15 patients). The low-risk group (n = 825) had 1.5% complications; moderate risk (n = 2,221) 4.9%; high risk (n: 458) 12% (p < 0.001). The analysis of the retrospective data (n = 2953) was validated with prospective (n = 551) using the Hosmer-Lemeshow test, showed that the predicted values are similar to those observed. Complications continue to occur despite the evolution of the technique. The score was useful for stratifying patients and knowing the probability of complication before the procedere.


Epidemiological, bacteriological and molecular studies on caseous lymphadenitis in Sirohi goats of Rajasthan, India.
Corynebacterium pseudotuberculosis is the causative agent of caseous lymphadenitis (CL), a chronic debilitating disease of goats. In the present study, a total of 575 goats of Sirohi breed on an organized farm situated in the semi-arid tropical region of Rajasthan, India were clinically examined. Pus samples from superficial lymph nodes of 27 (4.7%) adult goats presenting clinical lesions suggestive of CL were collected for bacteriological and molecular analyses. Of these goats, 51.9% yielded C. pseudotuberculosis on the basis of morphological, cultural and biochemical characteristics. A polymerase chain reaction (PCR) assay targeting proline iminopeptidase gene specific to C. pseudotuberculosis was developed that confirmed all 14 bacterial isolates. The specificity of the PCR product was confirmed by sequencing of the 551-bp amplicon in both senses, showing 98-100% homology with published sequences. Thus, overall prevalence rate based on clinical, bacterial culture and PCR assay were found to be 4.7%, 2.4% and 2.4%, respectively. The PCR assay developed in this study was found to be specific and rapid, and could be used for confirmation of CL in goats as an alternative method to generally cumbersome, time-consuming and less reliable conventional methods.