Social context and loneliness in an epidemiological youth sample using the Experience Sampling Method.
Previous research has shown the relationship between loneliness and affect, as well as the relationship between trait loneliness and state loneliness. However, none has investigated how social context affects the association between loneliness and affect. The current study aims to examine the association between trait loneliness, state loneliness and momentary affects in different social contexts. Participants aged 15-24 were randomly recruited from a Hong Kong epidemiological study to participate in an Experience Sampling Method (ESM) study. The group was divided in two based on the mean trait loneliness score (UCLA Loneliness Scale) at baseline. State loneliness, momentary positive (PA) and negative affect (NA) and social context were assessed using ESM. Multilevel logistic regression was used to analyze the association between momentary affect, state loneliness and trait loneliness in various social contexts. HL (high lonely) and LL (low lonely) groups consisted of 79 participants (44.6%) and 98 participants (55.4%) respectively. HL group had lower PA and higher NA, as well as a higher state loneliness than LL group. HL group had a lower state loneliness when being with intimate company compared to alone. LL group only had a higher PA when being with intimate company compared to non-intimate company and alone respectively. Adolescents with high level of trait loneliness experienced higher PA, momentary loneliness and lower NA compared to those with low level of trait loneliness. The quality of social company is crucial in allowing one to experience different degrees of PA and momentary loneliness.


Design and synthesis of a selective EP4-receptor agonist. Part 2: 3,7-dithiaPGE1 derivatives with high selectivity.
To identify new highly selective EP4-agonists, further modification of the 16-phenyl moiety of 1 was continued. 16-(3-methoxymethyl)phenyl derivatives 13-(6q) and 16-(3-ethoxymethyl)phenyl derivatives 13-(7e) showed more selectivity and potent agonist activity than 1. 16-(3-methyl-4-hydroxy)phenyl derivative 18-(14e) demonstrated excellent subtype selectivity, while both its receptor affinity and agonist activity were less potent than those of 13-(6q). Structure-activity relationships (SARs) are also discussed.


The effect of hematocrit on visual platelet estimation.
Estimation of the number of platelets on Wright's-stained blood smear and from phase platelet counts on more than 1700 patients were analyzed to determine if there were statistical significance in various ranges of hematocrit values. F-test analysis showed no significant difference among these variations in hematocrit determinations.


Modern Elective Laparoscopic Cholecystectomy Carries Extremely Low Postoperative Infection Risk.
The studies that established historical rates of surgical infection after cholecystectomy predate the modern era of laparoscopy and routine prophylactic antibiotics. Newer studies have reported a much lower incidence of infections in "low-risk" elective, outpatient, laparoscopic cholecystectomies. We investigated the current rate of postoperative infections in these cases within a large, U.S. We retrospectively reviewed elective laparoscopic cholecystectomies from the 2016-2017 American College of Surgeons National Surgical Quality Improvement Program database. Our primary outcome was postoperative surgical site infection; secondary was Clostridium difficile infection. Logistic models evaluated the associations of patient and operation characteristics with these outcomes. Surgical infection occurred in 1.0% of cases (293/30,579). Cdifficile infection occurred in 0.1% (31 cases). In our adjusted multivariable models, other/unknown race/ethnicity, diabetes, hypertension, smoking, American Society of Anesthesiologists >2, operative minutes, and wound class 4 were associated with a significantly higher odds of surgical infection; no covariates were significantly associated with Cdifficile infection. In the setting of modern U.S. surgical practice, the incidence of infection after elective laparoscopic cholecystectomy is very low, on par with clean cases. Our study identified several patient characteristics that were strongly associated with surgical infection. Many of these are not included as risk factors in current guidelines for antibiotic prophylaxis and may help to identify those at higher risk for this rare complication.


[Natural resistance of the body in appendicular peritonitis in children].
It is found that in appendicular peritonitis, as the inflammatory process progresses, the protective functions of the organism are lowered, and the intensity of inflammatory changes is increased. The determination of the natural resistance status of the body in peritonitis in children may be used for an objective estimation of the process course, the efficacy of therapeutic measures and prognostication.


Fetal growth restriction inhibits childhood growth despite catch-up in discordant identical twins: an observational cohort study.
Research suggests that postnatal catch-up growth after fetal growth restriction (FGR) occurs frequently. Yet, postnatal growth in singletons may be influenced by multiple factors. Identical twins with discordant prenatal growth, termed selective FGR (sFGR), can be regarded as a natural experiment eliminating these sources of bias. Observational cohort study. Monochorionic twins with sFGR born between 2002 and 2017 (aged 3-17 years) were eligible. Growth measurements (height, weight, head circumference, and body mass index) were performed at follow-up. Detailed growth curves documented by a systematic primary care system in the Netherlands were collected. Measurements were converted to standard deviation scores (SDSs). A mixed-effects model was used to assess within-pair SDS difference and individual height SDS relative to target height SDS. Forty-seven twin pairs (94 children) were included at a median age of 11 (interquartile range 8-13) years. At the last measurement, smaller twins at birth had a lower height SDS [-0.6 vs -0.3, P < .001, median difference 0.5 (95%CI 0.4-0.7)], lower weight SDS [-0.5 vs -0.1, P < .001, median difference 0.8 (95%CI 0.5-1.0)], and lower head circumference SDS [-0.5 vs 0.2, P < .001, median difference 0.8 (95%CI 0.6-0.9)] compared to larger twins. These differences persisted until the age of 17. Smaller twins showed rapid catch-up growth in the first 2 years and reached their target height range between 8 and 11 years. Identical twins with discordant prenatal growth maintain a modest but significant difference in height, weight, and head circumference, indicating a persistent, inhibitory effect of an adverse intrauterine environment on childhood growth.


Exosomes derived from immunogenically dying tumor cells as a versatile tool for vaccination against pancreatic cancer.
Despite tremendous progress achieved in immunotherapy, many critical challenges in treating pancreatic ductal adenocarcinoma (PDAC) persist. Considering the poor vascularization of PDAC, after intramuscular administration exosomes can targeted deliver "cargos" to pancreatic tumors and bypass obstructions of the intrinsic overexpressed stroma through lymphatics. Herein, we propose a strategy to derive exosomes from immunogenically dying tumor cells and exploit their properties for several purposes, including antigen presentation, adjuvant supply, and "cargo" delivery of vaccines against pancreatic cancer via intramuscular injection. To enhance the immunostimulatory effects, the MART-1 peptide is modified to the exosomes to expand T-cell-related responses. Furthermore, CCL22 siRNA is electroporated into the exosomes (referred to as spMEXO) to hinder the CCR4/CCL22 axis between DCs and Tregs, thereby suppressing Treg expansion. Both in vitro and in vivo studies demonstrate that spMEXO can serve as an effective prophylactic vaccine to delay tumor growth, whereas combining spMEXO with PDAC first-line chemotherapeutics (co-administration of gemcitabine with albumin-paclitaxel) demonstrated significantly enhanced therapeutic effects in established PANC-02 tumors. Therefore, the present work provides an effective strategy to employ cancer vaccines through intramuscular injection in PDAC and highlights the potential of exosomes derived from immunogenically dying tumor cells as a versatile tool to develop nanovaccines for immunotherapy.


Convergent synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) by the H-phosphonate approach.
Phosphorodiamidate morpholino oligonucleotides (PMOs) are a promising type of antisense oligonucleotides, but their challenging synthesis makes them difficult to access. This research presents an efficient synthetic approach for PMOs using the H-phosphonate approach. The use of phosphonium-type condensing reagents significantly reduced coupling times compared with the current synthetic approach. Furthermore, phosphonium-type condensing reagents facilitated the fragment condensation of PMO, synthesizing up to 8-mer containing all four nucleobases with remarkable coupling efficacy. This is the first report on the convergent synthesis of PMOs. This approach would facilitate the large-scale synthesis of PMOs and accelerate their popularity and accessibility as a next-generation therapy.


Chromosome aberration frequencies and chromosome instability in mice after long-term exposure to low-dose-rate gamma-irradiation.
Chronological changes of chromosome aberration rates related to accumulated doses in chronically exposed humans and animals at a low-dose-rate have not been well studied. C3H female specific pathogen-free mice (8 weeks of age) were chronically irradiated. Chromosome aberration rate in mouse splenocytes after long-term exposure to low-dose-rate (LDR) gamma-rays was serially determined by conventional Giemsa method. Incidence of dicentrics and centric rings increased almost linearly up to 8000 mGy following irradiation for about 400 days at a LDR of 20 mGy/day. Clear dose-rate effects were observed in the chromosome aberration frequencies between dose rates of 20 mGy/day and 200 Gy/day. Furthermore, the frequencies of complex aberrations increased as accumulated doses increased in LDR irradiation. This trend was also observed for the incidences of micronuclei and trisomies of chromosomes 5, 13 and 18 in splenocytes, detected by micronucleus assay and metaphase fluorescence in situ hybridization (FISH) method, respectively. Incidences of 2-4 micronuclei and trisomy increased in mouse splenocytes after irradiation of 8000 mGy at a LDR of 20 mGy/day. These complex chromosome aberrations and numerical chromosome aberrations seem to be induced indirectly after radiation exposure and thus the results indicate that continuous gamma-ray irradiation for 400 days at LDR of 20 mGy/day induced chromosomal instability in mice. These results are important to evaluate the biological effects of long-term exposure to LDR radiation in humans.


Preliminary results of anatomic lung resection using energy-based tissue and vessel coagulative fusion technology.
Mechanical stapling devices have been established as the mainstay of therapy in the selective isolation and division of bronchial and vascular structures during anatomic lung resection. Few data are available regarding the application of energy-based tissue fusion technology during anatomic lung resection. In the present study, we evaluated the use of energy-based instruments for the division of the pulmonary arterial and venous branches during anatomic lung resection. Anatomic lung resection (segmentectomy or lobectomy) was performed using energy-based coagulative fusion technology. A low-profile jaw can be used to facilitate dissection in both open and video-assisted thoracic surgery cases, applying a seal 6 mm wide by 22 mm in length. Two energy applications were applied to the arterial and venous branches before vessel division. The bipolar tissue fusion system was used in 211 patients between 2008 and 2010 (104 lobectomies and 107 anatomic segmentectomies). Initially, we used a device with a smaller, curved jaw (n = 12), producing a 3.3- to 4.7-cm seal. No arterial dehiscences and 2 partial venous dehiscences that were recognized and controlled intraoperatively occurred. For the remaining cases, we used a new device with a larger jaw that applied a seal 6 mm wide by 22 mm in length. No arterial or venous dehiscences (vessel size range, 0.4-1.2 cm) occurred. The bipolar tissue fusion system provided safe and reliable control of pulmonary arterial and venous branches during anatomic lung resection. The use of energy-based tissue fusion technology represents a reasonable alternative to mechanical stapling devices during anatomic lung resection.


Global paediatric advanced life support: improving child survival in limited-resource settings.
Nearly all global mortality in children younger than 5 years (99%) occurs in developing countries. The leading causes of mortality in children younger than 5 years worldwide, pneumonia and diarrhoeal illness, account for 1·396 and 0·801 million annual deaths, respectively. Although important advances in prevention are being made, advanced life support management in children in developing countries is often incomplete because of limited resources. Existing advanced life support management guidelines for children in limited-resource settings are mainly empirical, rather than evidence-based, written for the hospital setting, not standardised with a systematic approach to patient assessment and categorisation of illness, and taught in current paediatric advanced life support training courses from the perspective of full-resource settings. In this Review, we focus on extension of higher quality emergency and critical care services to children in developing countries. When integrated into existing primary care programmes, simple inexpensive advanced life support management can improve child survival worldwide.


Diffusion approximations of the two-locus Wright-Fisher model.
Diffusion approximations are established for the multiallelic, two-locus Wright-Fisher model for mutation, selection, and random genetic drift in a finite, panmictic, monoecious, diploid population. All four combinations of weak or strong selection and tight or loose linkage are treated, though the proof in the case of strong selection and loose linkage is incomplete. Under certain conditions, explicit formulas are obtained for the stationary distributions of the two diffusions with loose linkage.


Phosphate transport in Neurospora. Derepression of a high-affinity transport system during phosphorus starvation.
In addition to the constitutive, low-affinity phosphate-transport system described previously, Neurospora possesses a second, high-affinity system which is derepressed during phosphorus starvation. At pH 5.8, System ii has a K1/2 of about 3muM and a Jmax of 5.2 mmol/1 cell water per min. System ii reaches maximal activity after about 2 h of growth in phosphorus-free minimal medium. Its formation is blocked by cycloheximide and, once made, it appears to turn over rapidly. Addition of cycloheximide to fully derepressed cultures results in the decay of System ii with a t1/2 of 14 min, very similar to the turnoacteriol. 95, 959-966) for tryptophan transport in Neurospora. Thus, these transport systems appear to be regulated by a balance between synthesis and breakdown, as affected by intracellular pools of substrate or related compounds.


Relativistic acceleration of charged particles in uniform and mutually perpendicular electric and magnetic fields as viewed in the laboratory frame.
We obtain exact solutions in the laboratory frame for the relativistic position, velocity, and energy of a charged particle moving in constant, uniform, and mutually perpendicular electromagnetic fields. We also obtain an exact equation relating the proper time and the laboratory time, and examine all these quantities in the large and small time limits. Working in the laboratory frame makes the accelerated motion that can occur when /E/ > or = c/B/ easier to analyze and understand.


A novel protein associated with citrus blight has sequence similarities to expansin.
A protein associated with citrus blight (CB), a disease of unknown cause, was partially characterized. The 12 kDa protein, designated p12, is diagnostic of CB and is present in leaves and xylem fluid from roots and stems of CB-affected trees. The protein, and up to six other CB-specific proteins, are readily detected by SDS-PAGE of xylem fluid from CB-affected trees. The partial N-terminal amino acid sequence of p12 was found to be unique based on database searches. A cDNA library from CB-affected root cambium was screened with a 60 bp fragment, obtained by PCR amplification of cDNA with degenerate primers designed using the amino acid sequence of p12, and two clones were selected. These clones were sequenced revealing a 674 nucleotide cDNA with a 393 nt ORF which included sequence predicted by the N-terminal amino acid sequence of p12. The amino acid sequence based on the p12 ORF was found to be up to 49% similar and 31% identical to expansins. Bacterial expression of the cloned ORF, which encodes an 11.8 kDa protein plus an N-terminal hydrophobic signal peptide, produced an immunoreactive protein of the expected size. By northern blot analysis, it was determined that p12 transcripts are present in root and stem cambium, but not in leaves of CB-affected trees, suggesting transport of the protein to leaves. Southern hybridization analysis of citrus genomic DNA indicated that p12 is a citrus encoded protein.


High-performance liquid chromatographic determination of rufloxacin and its main active metabolite in biological fluids.
A high-performance liquid chromatographic method is described for the determination of a fluoroquinolone, rufloxacin, and its N-desmethyl metabolite in plasma, urine and bile. Samples are chromatographed on a poly(styrene-divinylbenzene) column, the eluate being monitored with a fluorescence detector. The method was validated and a detection limit of 10 ng/ml for both rufloxacin and its metabolite in all the biological matrices considered was found. The method was successfully applied in pharmacokinetic studies.


Imaging of central nervous system emergencies in oncology.
Central nervous system (CNS) may be predisposed to devastating complications in cancer patients which may add to morbidity and mortality in this group. Majority of the complications are vascular in nature due to the altered coagulation profile and pro-inflammatory state in these patients. However, there are a host of other conditions which may affect the clinical course of these patients including metabolic and toxic encephalopathies, infections, and paraneoplastic syndromes. Moreover, multimodality management of these patients, which is often used in majority of the cancers, exposes them to treatment related complications. This pictorial review aims to enlighten the reader regarding the various complications affecting the CNS as seen at our tertiary cancer care institute. We aim to highlight the emergent nature of these complications and the need to identify them quickly and accurately on imaging which helps to institute early appropriate management and prevents further morbidity and mortality.


Modification of the American Burn Association injury severity grading system.
This study evaluated the regional burn health care system of the Commonwealth of Virginia using the criteria for optimal care of the burn patient designated by the American Burn Association. The data base for this evaluation was hospital records of seven hospitals in Virginia. The major shortcoming of the designated criteria was the grading system for the severity of burn injury. Using the criteria designated by the American Burn Association, a large number of minor burn injuries were judged erroneously to be major burn injuries. A modification of the American Burn Association's injury severity grading system is proposed which more precisely identifies the minor burn injury.


Functional and structural limb length discrepancies: evaluation and treatment.
The examining physician should have a high index of suspicion when evaluating patients with lower extremity and/or back pain so that the diagnosis of leg length inequality is not overlooked. If an organized and systematic physical examination is performed, the practioner will become more comfortable and competent in the diagnosis of limb asymmetry. Once the diagnosis of limb length asymmetry is made the further classification of functional versus structural limb length discrepancy will dictate what treatment will be indicated. The structural asymmetries are evaluated by the indirect method of measurement and treatment with a heel lift approximately half the measured asymmetry initially. The functional asymmetries are evaluated by the flexion and pronation tests and treated with a properly posted orthotic.


A combined neurofibroma-granular cell tumor of the middle cranial fossa.
A case of a combined neurofibroma-granular cell tumor in a 52 years old gunsmith is presented. The tumor developed after an intracranial trigeminal nerve operation 25 years previously. The solid tumor in the left middle cranial fossa had displaced and infiltrated the temporal lobe. It had expanded via the optic nerve into the left orbit, and further the apex partis petrosae was destroyed. The neurofibroma part shows histological aspects of malignancy, the granular cell tumor, considering its infiltrating and destructive growth, may be regarded as malignant as well. In intermingling portions of the tumor, transitional types of fiber-like and granular cells are prominent. In the peripheral zone of the tumor apparently reactively proliferated polynuclear astrocytes are seen with occasionally intracytoplasmatic lymphocytes (emperipolesis?). A short review of the literature and the theories concerning the histogenesis of the granular cell tumor is given. Whereas most authors in recent years suggest a Schwann cell origin, based on electron microscopic findings, this intermediate tumor type motivates us to postulate a mesodermal origin of the granular cell tumor. The question of viral influence is discussed briefly.


Anti-nociceptive activity of nitric oxide synthase inhibitors in the mouse: dissociation between the effect of L-NAME and L-NMMA.
The anti-nociceptive effect of selective inhibitors of nitric oxide synthase has been assessed in a formalin-induced paw-licking model in mice. L-NG-Nitro arginine methyl ester (L-NAME) but not L-NG-monomethyl arginine (L-NMMA) exhibited anti-nociceptive activity in both the early and late phases of paw licking following intraperitoneal administration. The effect on the late phase response was more pronounced. L-NAME (0.1-100 micrograms) and L-NG-nitro arginine base (L-NOARG; 10 micrograms) but not D-NAME (10 micrograms) were also anti-nociceptive following intracerebroventricular administration. L-NAME (10 micrograms) administered by this route did not influence locomotor activity. L-NMMA was inactive at doses up to 40 micrograms by this route. At higher doses (75-200 micrograms) L-NMMA produced a similar and non-dose related reduction in early/late phase paw-licking time. D-NMMA (100 micrograms) was inactive. The greater anti-nociceptive effect of L-NAME in this model accords with recently published biochemical data indicating that L-NAME is several orders of magnitude more potent than L-NMMA as an inhibitor of brain nitric oxide synthase. These data support the use of L-NAME as a selective tool to investigate the central pharmacological effects of nitric oxide.


Synthesis of glucose-templated lysine analogs and incorporation into the antimicrobial dipeptide sequence kW-OBn.
The synthesis of two glucose-templated (GlcT) lysine analogs GlcTK and GlcTk in which the side chain of D- and L-lysine (k and K) is conformationally constrained via incorporation into a D-glucose scaffold is described. A key-step in the synthesis is a high yielding, reductive ring opening of an exocyclic glucose-derived epoxide to form a alpha-hydroxy ester that can be converted into GlcTK and GlcTk. To demonstrate the use of these building blocks in peptide synthesis, we replaced D-lysine in the antimicrobial dipeptide sequence kW-OBn (W=L-tryptophan) and determined the antibacterial activity against various gram-positive and gram-negative organisms. Our results show that the replacement of D-lysine by unprotected GlcTk in dipeptide kW-OBn results in reduced antibacterial activity.


In vitro characterization and molecular dynamics simulation reveal mechanism of 14-3-3ζ regulated phase separation of the tau protein.
As a major microtubule-associated protein, tau is involved in the assembly of microtubules in the central nervous system. However, under pathological conditions tau assembles into amyloid filaments. Liquid droplets formed by liquid-liquid phase separation (LLPS) are a recently identified assembly state of tau and may have a major effect on the physiological function of tau and the formation of tau aggregates. 14-3-3 proteins are ubiquitously expressed in various tissues and regulate a wide variety of biological processes. In this work, we demonstrate that 14-3-3ζ is recruited into tau droplets and regulates tau LLPS by in vitro assays. While the mobility of tau molecules inside the droplets is not affected in the presence of 14-3-3ζ, the amount and size of droplets can vary significantly. Mechanistic studies reveal that 14-3-3ζ regulates tau LLPS by electrostatic interactions and hydrophobic interactions with the proline-rich domain and the microtubule-binding domain of tau. Surprisingly, the disordered C-terminal tail rather than the amphipathic binding groove of 14-3-3ζ plays a key role. Our findings not only provide a novel dimension to understand the interactions between 14-3-3 proteins and tau, but also suggest that 14-3-3 proteins may play an important role in regulating the LLPS of their binding partners.


Functional resistance training during walking: Mode of application differentially affects gait biomechanics and muscle activation patterns.
Task-specific loading of the limbs-termed as functional resistance training-is commonly used in gait rehabilitation; however, the biomechanical and neuromuscular effects of various forms of functional resistance training have not been studied systematically. This information is crucial for correctly selecting the appropriate mode of functional resistance training when treating individuals with gait disorders. To comprehensively evaluate the biomechanical (i.e., joint moment and power) and muscle activation changes with different forms of functional resistance training that are commonly used in clinics and research using biomechanical simulation-based analyses. We developed simulations of functional resistance training during walking using OpenSim (Gait2354, 23 degrees of freedom and 54 muscles) and custom MATLAB scripts. We investigated five modes of functional resistance training that have been commonly used in clinics or in research: (1) a weight attached at the ankle, (2) an elastic band attached at the ankle, (3) a viscous device attached to the hip and knee, (4) a weight attached at the pelvis, and (5) a constant backwards pulling force at the pelvis. Lower-extremity joint moments and powers were computed using inverse dynamics and muscle activations were estimated using computed muscle control while walking with each device under multiple resistance levels: normal walking with no resistance, and walking with 30, 60, and 90 Newtons of resistance. The results indicate that the way in which resistance is applied during gait training differentially affects the internal joint moments, powers, and muscle activations as well as the joints and phase of the gait cycle where the resistance was experienced. The results highlight the importance of understanding the joints and muscles that are targeted by various modes of functional resistance training and carefully choosing the best mode of training that meets the specific therapeutic needs of the patient.


Down-regulated lncRNA HOTAIR alleviates polycystic ovaries syndrome in rats by reducing expression of insulin-like growth factor 1 via microRNA-130a.
It has been found that long noncoding RNA HOTAIR, microRNA-130a (miR-130a) and insulin-like growth factor 1 (IGF1) expression are associated with ovarian cancer, thus, we hypothesised that the HOTAIR/miR-130a/IGF1 axis might associate with endocrine disorders and biological behaviours of ovarian granulosa cells in rat models of polycystic ovary syndrome (PCOS). PCOS rat models were established by injection of dehydro-isoandrosterone, followed by treatment of si-HOTAIR, oe-HOTAIR, miR-130a mimics or miR-130a inhibitors. Serum hormonal levels were determined to evaluate endocrine conditions. The effect of HOTAIR and miR-130a on activities of isolated ovarian granulosa cells was assessed, as well as the involvement of IGF1.In the ovarian tissues and granulosa cells of PCOS rat models, highly expressed HOTAIR and IGF1 and poorly expressed miR-130a were identified. In response to oe-HOTAIR, serum levels of E2 , T and LH were increased and serum levels of FSH were reduced; the proliferation of granulosa cells was reduced and apoptosis was promoted; notably, expression of miR-130a was reduced while expression of IGF1 was increased. The treatment of si-HOTAIR reversed the situation. Furthermore, the binding of HOTAIR to miR-130a and targeting relationship of miR-130a and IGF1 were confirmed. LncRNA HOTAIR up-regulates the expression of IGF1 and aggravates the endocrine disorders and granulosa cell apoptosis through competitive binding to miR-130a in rat models of PCOS. Based on our finding, we predict that competitive binding of HOTAIR to miR-130a may act as a novel target for the molecular treatment of PCOS.


The indirect effect of self-compassion in the association between autistic traits and anxiety/depression: A cross-sectional study in autistic and non-autistic adults.
Previous research on non-autistic adults suggests self-compassion may serve to reduce mental health problems and promote psychological well-being. Correlations between autistic traits and self-compassion have been observed in non-clinical populations. In this study, we were interested in extending previous research by exploring relationships between autistic traits, self-compassion and anxiety/depression in autistic adults without intellectual disability. The findings revealed that on average autistic people reported lower self-compassion than non-autistic people. Once we accounted for levels of self-compassion in our statistical model, this resulted in a complete loss of statistical significance in the relationships between autistic traits and anxiety/depression. Self-compassion may be a useful target for clinical intervention in autistic adults with co-occurring mental health difficulties.


Preference for human direct gaze in infant chimpanzees (Pan troglodytes).
We studied gaze perception in three infant chimpanzees (Pan troglodytes), aged 10-32 weeks, using a two-choice preferential-looking paradigm. The infants were presented with two photographs of a human face: (a) with the eyes open or closed, and (b) with a direct or an averted gaze. We found that the chimpanzees preferred looking at the direct-gaze face. However, in the context of scrambled faces, the infants showed no difference in gaze discrimination between direct and averted gazes. These findings suggest that gaze perception by chimpanzees may be influenced by the surrounding facial context. The relationship between gaze perception, face processing, and the adaptive significance of gaze perception are discussed from an evolutionary perspective.


[Need for psychosocial care in in-patients with tumour disease. Investigations conducted in a clinic specializing in tumour surgery].
Patients with tumour disease are in particularly stressful situation at all times. The aim of the present study was to find what proportion of patients on a surgical oncology ward would also benefit from psycho-oncological care. Within a period of 6 months (IIIrd and IVth quarters of 2004) 406 of our tumour patients were questioned with the aid of a method (Po-Bado) developed specifically for use with such patients. According to this inquiry, it can be assumed that 41.4% of tumour patients are in need of professional psycho-oncological support. Patients who are in hospital for diagnostic procedures to confirm or exclude the suspicion of tumour disease have a greater need for such support (48.7%) than do patients who have been admitted for a scheduled operation (37.3%). Correlations were found between the need for this therapy and different disease situations. The prevalence of need was highest among patients with a second tumour, in whom it was 66.7%. The type of tumour disease also had an influence whether psycho-oncological care was indicated. The study revealed that patients with malignant soft-tissue tumours (49%) and patients with tumours of the upper digestive organs (48.7%) find the mental stress more difficult to cope with than patients who are in hospital for treatment of malignant skin tumours (31.8%) or malignant tumours of the mammary gland (38.7%). These results suggest that an adequate psycho-oncologic diagnostic at the start of a stationary stay are reasonable. This is a precondition for a well-directed psycho-oncologic intervention in order to enhance the disease accomplishment but at the same time the target-oriented supply of psycho-oncologic care in hospitals is a limited resource.


Prevalence of gastroparesis in diabetic patients: a systematic review and meta-analysis.
Although there was no significant heterogeneity in the meta-publication, sensitivity analyses revealed significant heterogeneity. Overall, the prevalence was higher in women (N = 6, R = 4.6%, 95% CI 3.1%, 6.0%, and I2 = 99.8%) than in men (N = 6, R = 3.4%, 95% CI 2.0%, 4.7%, and I2 = 99.6the %); prevalence of type 2 diabetes (N = 9, R = 12.5%, 95% CI 7.7%, 17.3%, and I2 = 95.4%) was higher than type 1 diabetes (N = 7, R = 8.3%, 95% CI 6.4%, 10.2%, and I2 = 93.6%); the prevalence of DGP was slightly lower in DM patients aged over 60 years (N = 6, R = 5.5%, 95% CI 3.3%, 7.7%, and I2 = 99.9%) compared to patients under 60 years of age (N = 12, R = 15.8%, 95% CI 11 15.8%, 95% CI 11.4%, 20.2%, and I2 = 88.3%). In conclusion, our findings indicate that the combined estimated prevalence of gastroparesis in diabetic patients is 9.3%. However, the sensitivity of the results is high, the robustness is low, and there are significant bias factors. The subgroup analysis revealed that the prevalence of DM-DGP is associated with factors such as gender, diabetes staging, age, and study method.


Charting plant interactomes: possibilities and challenges.
Protein-protein interactions are essential for nearly all cellular processes. Therefore, an important goal of post-genomic research for defining gene function and understanding the function of macromolecular complexes involves creating 'interactome' maps from empirical or inferred datasets. Systematic efforts to conduct high-throughput surveys of protein-protein interactions in plants are needed to chart the complex and dynamic interaction networks that occur throughout plant development. However, no single approach can build a complete map of the interactome. Here, we review the utility and potential of various experimental approaches for creating large-scale protein-protein interaction maps in plants. Bioinformatics approaches for curating and assessing the confidence of these datasets through inter-species comparisons will be crucial in achieving a complete understanding of protein interaction networks in plants.


Studies on Culicoides species of Nigeria. VII. The biology of some Nigerian Culicoides species.
During field investigations into the biology of Culicoides species of Nigeria, 8,795 newly emerged Culicoides comprising of 20 species were caught with emergence traps at the Teaching and Research Farm of the University of Ibadan. Culicoides imicola Kieffer was the most predominant followed by C. quinquelineatus Goetghebuer and C. endelini Endeline. Two groups of Culicoides species were recognized. These were those breeding only during the rains with emergence peaks in June and August and those breeding throughout the year with low emergence during the dry season. Rainfall, temperature, relative humidity, the soil pH and its organic and mineral contents were found to influence Culicoides breeding. Low or traces of rainfall extended over 1-2 h were observed to be more favourable for Culicoides development than heavy rainfall which ended quickly within 1/2 h. A greater proportion of the Culicoides emerged during the night. It was concluded that the optimum temperature range for Culicoides emergence was 23-27 degrees C and optimum range of relative humidity 80-90%. Larvae were abundant on the soil throughout the year with a peak during the dry season; the seasonal abundance of pupae was similar to that of newly emerged adults. Although the fat-bodies of all the dissected newly emerged Culicoides were large, full and conspicious, those of about half of the Culicoides dissected in February and March contained larger, fuller and more conspicuous fat-bodies. It is suggested that the presence of such accumulated fatbodies during the onset of the rains immediately after the hot dry season signifies hibernation in these species.


Factors associated with elevated pulmonary arterial pressure levels on the echocardiographic assessment in patients with prior pulmonary embolism.
Factors associated with the detection of raised systolic pulmonary artery pressure (sPAP) levels in patients with a prior episode of pulmonary embolism (PE) are not well known. We used the RIETE Registry database to identify factors associated with the finding of sPAP levels ≥50 mm Hg on trans-thoracic echocardiography, in 557 patients with a prior episode of acute, symptomatic PE. Sixty-two patients (11.1%; 95% CI: 8.72-14.1) had sPAP levels ≥50 mm Hg. These patients were more likely women, older, and more likely had chronic lung disease, heart failure, renal insufficiency or leg varicosities than those with PAP levels <50mm Hg. During the index PE event, they more likely had recent immobility, and more likely presented with hypoxemia, increased sPAP levels, atrial fibrillation, or right bundle branch block. On multivariate analysis, women aged ≥70 years (hazard ratio [HR]: 2.0; 95% CI: 1.0-3.7), chronic heart or chronic lung disease (HR: 2.4; 95% CI: 1.3-4.4), atrial fibrillation at PE presentation (HR: 2.8; 95% CI: 1.3-6.1) or varicose veins (HR: 1.8; 95% CI: 1.0-3.3) were all associated with an increased risk to have raised sPAP levels. Chronic heart disease, varicose veins, and atrial fibrillation were independent predictors in women, while chronic heart disease, atrial fibrillation, a right bundle branch block or an S1Q3T3 pattern on the electrocardiogram were independent predictors in men. Women aged ≥70 years more likely had raised sPAP levels than men after a PE episode. Additional variables influencing this risk seem to differ according to gender.


Optimizing the extraction of bioactive compounds from pu-erh tea (Camellia sinensis var. assamica) and evaluation of antioxidant, cytotoxic, antimicrobial, antihemolytic, and inhibition of α-amylase and α-glucosidase activities.
The aims of this study were to quantify and optimize the extraction of total phenolic content (TPC), total flavonoids (TF) and antioxidant activity (AA) of aqueous pu-erh (Camellia sinensis var. assamica) extracts, as well as to compare the optimized pu-erh tea extract (OPT) with toasted mate (Ilex paraguariensis), black and green (Camellia sinensis) teas. The optimization process increased the TPC and the ferric reducing antioxidant power (FRAP). The results showed that the green tea extract presented the highest values for TPC and antioxidant capacity. The pasteurized OPT showed lower TPC and TF, and higher FRAP, DPPH and Cu2+ chelating ability compared to the non-pasteurized OPT. The lyophilized OPT showed inhibition of lipid peroxidation in Wistar rat brain homogenate and displayed antibiofilm activity against Enterococcus faecalis ATCC 25212 and 19433, and Staphylococcus aureus ATCC 25923. Additionally, lyophilized OPT presented cytotoxic and antiproliferative effects against tumor cell lines (Caco-2, A549 and HepG2), inhibited the production of reactive oxygen species in A549 and IMR90 cells, and presented antihemolytic activity in human erythrocytes. The lyophilized OPT inhibited α-glucosidase (IC50 = 47.0 µg/mL) and α-amylase at 30.0 mg/mL. The main compounds detected in OPT were gallic acid, caffeine and theobromine.


Paternal postnatal depression and received midwife, child health nurse, and maternal support: A cross-sectional analysis of primiparous and multiparous fathers.
Fathers want more professional and social support during the transition to fatherhood. It is unclear if these supports are associated with decreased depressive symptoms in fathers of infants. The aim of the current study was to assess if fathers' self-reported received professional and social support were related to changes in the odds for having depressive symptoms, with interaction terms focusing on differences of support based on the fathers' parity. In total, 612 fathers from Sweden completed a Facebook-advertised anonymous online survey. The Edinburgh Postnatal Depression Scale was used to detect depressive symptoms (≥10 points). Multiple imputation of missing data was performed. Logistic regressions were used, with interaction terms for fathers' parity. Around 21% of fathers had depressive symptoms. There were no associations between depressive symptoms frequencies and paternal parity. Fathers reported fewer depressive symptoms when they received professional support from the prenatal midwife (OR = .39, p = .007), labor/birth midwife/nurse team (OR = .42, p = .021), and child health nurse (OR = .25, p = .001), as well as social support from their partner and if they had a higher income (odds ratios vary in different models). Multiparous fathers received significantly less professional and social support and were less frequently invited to child health visits than primiparous fathers. The data collected was cross-sectional; therefore, causal links cannot be determined. Both primiparous and multiparous fathers should receive postnatal depression screenings and interventions to help reduce their depressive symptoms.


Endovascular salvage of failing arterio-venous fistulas utilising sirolimus eluting balloons: Six months results from the ISABELLA trial.
Aim of this pilot clinical study was to evaluate the safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-eluting balloon (SEB) for improving failing arterio-venous fistulas (AVF) patency in Asian haemodialysis patients. Prospective single-centre, multi-investigator, non-consecutive, non-blinded single arm trial. Forty end-stage renal failure Asian patients with a dysfunctional AVF underwent SEB angioplasty between May and November 2020. All stenotic lesions were prepared with high pressure non-compliant balloon angioplasty prior to SEB angioplasty. Endpoints of interest included target lesion primary patency and circuit access patency and safety through 30 days. All patients received dual antiplatelet therapy for 1 month and were followed up with Duplex ultrasound at 6 months. There was one subject dropout so final n = 39 patients (mean age 65.0 ± 11.9; males = 26 (66.7%)) and n = 43 target lesions treated. Main indication for intervention was dropping access flow (24/39; 61.5%) and most common target lesion was in the juxta-anastomosis (24/43; 54.5%). There was 100% technical and procedural success. There were no adverse events related to the SEB. Target lesion primary patency rates at 3 and 6 months were 39/41 (95.1%) and 28/39 (71.8%) respectively. Access circuit patency rates at 3 and 6 months were 35/37 (94.6%) and 22/35 (62.9%) respectively. There were 3 (7.7%) deaths all attributable to patients' underlying co-morbidities. Fistuloplasty using the novel Selution SLR™ SEB for dysfunctional AVF circuits seems a safe and effective modality in Asian haemodialysis patients at 6 months but larger randomised controlled studies are required now to determine its true efficacy against plain balloon angioplasty.


ECG-gated pulmonary artery CTA for evaluation of right ventricular function in patients with acute pulmonary embolism.
To evaluate right ventricular function in patients with acute pulmonary embolism (APE) using electrocardiogram-gated CTA and to discuss the clinical value of pulmonary artery CTA PATIENTS AND METHODS: Based on death risk evaluation, 86 APE patients were divided into high-risk group (n=46) and non-high-risk group (n=40). The CT pulmonary embolism (PE) index and parameters of right ventricular function were analyzed from the CTPA images and compared between the two groups. Potential correlation between the two was also discussed. CT PE index (median 24.69%) of the high-risk group was obviously higher than that of the non-high-risk group (median 8.58%) (P<.05). Except the diameter of superior vena cava, all other parameters of right ventricular function were significantly different between the two groups (P<.05). CT PE index was correlated with the parameters of right ventricular function. ECG-gated pulmonary artery CTA is suitable for assessing the severity of APE and right ventricular function.


Renal excretion of lactate and magnesium in mitral valve prolapse.
A strong positive correlation between urinary magnesium and lactate was found in 17 magnesium-depleted patients with echocardiographically proved mitral valve prolapse. The strong correlation over all the range of urinary magnesium values and the significantly increased excretion of lactate suggest urinary magnesium loss in this syndrome.


Where PI3K/Akt meets Smads: the crosstalk determines human embryonic stem cell fate.
Coordinated interactions between signaling networks govern the balance of cell fate decisions in human embryonic stem cells. In this issue, Singh et al. (2012) report that PI3K/Akt signaling switches Activin/Smad activity between pro-self-renewal and prodifferentiation by regulating ERK and GSK3β/β-catenin signaling.


CHD2-related epilepsy: novel mutations and new phenotypes.
The aim of this report was to refine the genotypes and phenotypes of chromodomain helicase DNA-binding protein 2 (CHD2)-related epilepsy. Seventeen patients with CHD2 mutations were enrolled. CHD2 mutations were identified by application of next-generation sequencing of epilepsy or whole exome sequencing. Sixteen mutations were identified, among which 15 have not yet been reported. Thirteen mutations were de novo. Age at seizure onset ranged from 3 months to 10 years 5 months. Seizures observed were generalized tonic-clonic, myoclonic, atonic, atypical absence, focal, and myoclonic-atonic. Epileptic spasms occurred in two patients. Developmental disability was present in 14 patients. Autism features were observed in seven patients. Video electroencephalogram was abnormal in 15 patients. Five patients were diagnosed with non-specific epileptic encephalopathy, two with epilepsy with myoclonic-atonic seizures, two with Lennox-Gastaut syndrome, two with febrile seizures plus, and one with West syndrome. Seizures were controlled in nine patients. Q1392TfsX17 may be a hot-spot mutation of CHD2. West syndrome was observed as a new phenotype of CHD2 mutation. The severity of the phenotypes of CHD2 mutations ranged from mild febrile seizures to severe epileptic encephalopathy. WHAT THIS PAPER ADDS: Q1392TfsX17 maybe the hot-spot mutation of CHD2. West syndrome could be a new phenotype of CHD2 mutation.


Impact of 5α-reductase inhibitor and α-blocker therapy for benign prostatic hyperplasia on prostate cancer incidence and mortality.
To investigate the use of 5α-reductase inhibitors (5ARIs) and α-blockers among men with benign prostatic hyperplasia (BPH) in relation to prostate cancer (PCa) incidence, severity and mortality. A retrospective 20-year cohort study in men residing in Saskatchewan, aged 40-89 years, with a BPH-coded medical claim between 1995 and 2014, was conducted. Cox proportional hazards regression was used to compare incidence of PCa diagnosis, metastatic PCa, Gleason score 8-10 PCa, and PCa mortality among 5ARI users (n = 4 571), α-blocker users (n = 7 764) and non-users (n = 11 677). In comparison with both non-users and α-blocker users, 5ARI users had a ~40% lower risk of a PCa diagnosis (11.0% and 11.4% vs 5.8%, respectively), and α-blocker users had an 11% lower risk of a PCa diagnosis compared with non-users. Overall, the incidence of metastatic PCa and PCa mortality was not significantly different among 5ARI or α-blocker users compared with non-users (adjusted hazard ratios [HR] of metastatic PCa: 1.12 and 1.13, respectively, and PCa mortality: 1.11 and 1.18, respectively, P > 0.05 for both drugs), but both 5ARI and a-blocker users had ~30% higher risk of Gleason score 8-10 cancer, adjusted HR 1.37, 95% confidence interval [CI] 1.03-1.82, P = 0.03, and adjusted HR 1.28, 95% CI 1.03-1.59, P = 0.02, respectively compared with non-users. The use of 5ARIs was associated with lower risk of PCa diagnosis, regardless of comparison group. Risk of high grade PCa was higher among both 5ARI users and α-blocker users compared with non-users; however, this did not translate into higher risk of PCa mortality.


Investigation of mutations in Fanconi anemia genes and malignancy predisposition in Brazilian patients.
This study proposed to identify Fanconi anemia (FA) mutations in Brazilian patients and to investigate their impact on clinical manifestations and malignancies onset. A total of 116 patients were screened for nine mutations in FANCA, FANCC, FANCG. Those with no mutations were investigated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing for FANCA, FANCC, FANCE, FANCF, FANCG, FANCD1/BRCA2. Genetic subtype was identified in 107/116 (78 FA-A, 8 FA-C, 13 FA-G, 8 FA-E), with only one mutation in 1/116, and no mutations in 9/116 patients. Before hematopoietic cell transplantation (HCT), malignancies were detected in 16/116 patients (14/78 FA-A, 01/08 FA-C, 01/08 FA-E), and 12 of them were hematological. Observed to expected ratio (O/E) of hematologic malignancy was 303.7 (95% CI = 148.6-458.7). This study allowed the identification of biallelic mutations in 91.4% of patients. FANCG and FANCC mutations had significantly earlier bone marrow failure onset, and FANCG severe cytopenia at diagnosis. Despite the inherent limitations of the small number of malignancy events in each genetic subtype, the hematologic malignancies O/E ratio was very high. Cumulative incidence of malignancy before HCT was higher in the third and fourth decades of life, considering HCT and death as competing risks. The cumulative incidence of HCT increased during the first decade, competing with malignancy development.


Retroelements in higher plants.
Representatives of several classes of retroelements have been characterized in a broad range of plant species, where they appear at variable and sometimes very high copy numbers. So far, only a very small number of plant elements have been shown to be active, and this activity seems to be restricted to specific situations of 'genomic shock'. Although it is not yet known whether the presence of retroelements is linked to the high level of variability found in plant genomes, it is now clear that retrotransposons are ancient and ubiquitous components of plant genomes, and could play an important role in plant evolution.


A Five-miRNA Panel Identified From a Multicentric Case-control Study Serves as a Novel Diagnostic Tool for Ethnically Diverse Non-small-cell Lung Cancer Patients.
Circulating microRNAs (miRNAs) are promising biomarkers for cancer detection. However, multiethnic and multicentric studies of non-small-cell lung cancer (NSCLC) are lacking. We recruited 221 NSCLC patients, 161 controls and 56 benign nodules from both China and America. Initial miRNA screening was performed using the TaqMan Low Density Array followed by confirming individually by RT-qPCR in Chinese cohorts. Finally, we performed a blind trial from an American cohort to validate our findings. RT-qPCR confirmed that miR-483-5p, miR-193a-3p, miR-25, miR-214 and miR-7 were significantly elevated in patients compared to controls. The areas under the curve (AUCs) of the ROC curve of this five-serum miRNA panel were 0.976 (95% CI, 0.939-1.0; P < 0.0001) and 0.823 (95% CI, 0.75-0.896; P < 0.0001) for the two confirmation sets, respectively. In the blind trial, the panel correctly classified 95% NSCLC cases and 84% controls from the American cohort. Most importantly, the panel was capable of distinguishing NSCLC from benign nodules with an AUC of 0.979 (95% CI, 0.959-1.0) in the American cohort and allowed correct prediction of 86% and 95% stage I-II tumors in the Chinese and American cohorts, respectively. This serum miRNA panel holds the potential for diagnosing ethnically diverse NSCLC patients.


Immune checkpoint activity regulates polycystic kidney disease progression.
Innate and adaptive immune cells modulate the severity of autosomal dominant polycystic kidney disease (ADPKD), a common kidney disease with inadequate treatment options. ADPKD has parallels with cancer, in which immune checkpoint inhibitors have been shown to reactivate CD8+ T cells and slow tumor growth. We have previously shown that in PKD, CD8+ T cell loss worsens disease. This study used orthologous early-onset and adult-onset ADPKD models (Pkd1 p.R3277C) to evaluate the role of immune checkpoints in PKD. Flow cytometry of kidney cells showed increased levels of programmed cell death protein 1 (PD-1)/cytotoxic T lymphocyte associated protein 4 (CTLA-4) on T cells and programmed cell death ligand 1 (PD-L1)/CD80 on macrophages and epithelial cells in Pkd1RC/RC mice versus WT, paralleling disease severity. PD-L1/CD80 was also upregulated in ADPKD human cells and patient kidney tissue versus controls. Genetic PD-L1 loss or treatment with an anti-PD-1 antibody did not impact PKD severity in early-onset or adult-onset ADPKD models. However, treatment with anti-PD-1 plus anti-CTLA-4, blocking 2 immune checkpoints, improved PKD outcomes in adult-onset ADPKD mice; neither monotherapy altered PKD severity. Combination therapy resulted in increased kidney CD8+ T cell numbers/activation and decreased kidney regulatory T cell numbers correlative with PKD severity. Together, our data suggest that immune checkpoint activation is an important feature of and potential novel therapeutic target in ADPKD.


Ionic liquids affect the adsorption of liposomes onto cationic polyelectrolyte coated silica evidenced by quartz crystal microbalance.
The worldwide use of ionic liquids (ILs) is steadily increasing, and even though they are often referred to as "green solvents" they have been reported to be toxic, especially toward aquatic organisms. In this work, we thoroughly study two phosphonium ILs; octyltributylphosphonium chloride ([P8444]Cl) and tributyl(tetradecyl)phosphonium chloride ([P14444]Cl). Firstly, the critical micelle concentrations (CMCs) of the ILs were determined with fluorescence spectroscopy and the optical pendant drop method in order to gain an understanding of the aggregation behavior of the ILs. Secondly, a biomimicking system of negatively charged unilamellar liposomes was used in order to study the effect of the ILs on biomembranes. Changes in the mechanical properties of adsorbed liposomes were determined by quartz crystal microbalance (QCM) measurements with silica coated quartz crystal sensors featuring a polycation layer. The results confirmed that both ILs were able to incorporate and alter the biomembrane structure. The membrane disrupting effect was emphasized with an increasing concentration and alkyl chain length of the ILs. In the extreme case, the phospholipid membrane integrity was completely compromised.


Protocol for using NoBadWordsCombiner to merge and minimize "bad words" from BLAST hits against multiple eukaryotic gene annotation databases.
Annotating protein-coding genes can be challenging, especially when searching for the best hits against multiple functional databases. This is partly because of "bad words" appearing as top hits, such as hypothetical or uncharacterized proteins. To help alleviate some of these issues, we designed a bioinformatics tool called NoBadWordsCombiner, which efficiently merges the hits from various databases, strengthening gene definitions by minimizing functional descriptions containing "bad words." Unlike other available tools, NoBadWordsCombiner is user friendly, but it does require users to have some general bioinformatics skills, including a basic understanding of the BLAST package and dash shell in Linux/Unix environments. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021a).


Single-stranded RNA viruses inactivate the transcriptional activity of p53 but induce NOXA-dependent apoptosis via post-translational modifications of IRF-1, IRF-3 and CREB.
To characterize the mechanisms underlying apoptosis induced by viral infection, transcriptional activation of genes encoding members of the 'BH3-only' family of proteins was analysed during the course of virus infection. Among these genes, only NOXA is transcriptionally activated by vesicular stomatitis virus (VSV), sendai virus (SV), measles virus, herpes simplex virus, or dsRNA and required for efficient apoptosis of cells. Transcriptional activation of NOXA by VSV or SV is independent of p53, but requires the presence of interferon regulatory factor 1 (IRF-1), IRF-3 and cAMP-responsive element binding protein (CREB). Binding to and transactivation of the NOXA promoter by each of these transcription factors is governed by post-translational modification involving different pathways for each factor. Thus, SV infection activates IRF-3 and CREB by phosphorylation triggered by Toll like receptor 3 signalling, and a pathway involving calcium-independent phopholipase A2, respectively. In addition transactivation induced by IRF-1 during viral infection correlates with a 10 kDa increase in its molecular weight, suggesting a covalent linkage with a previously unknown regulatory polypeptide.


Spatial memory of heterozygous staggerer (Rora(+)/Rora(sg)) versus normal (Rora(+)/Rora(+)) mice during aging.
Heterozygous staggerer mice (Rora(+)/Rora(sg)) and control mice (Rora(+)/Rora(+)) of the same C57BL/6J strain background were tested in a spontaneous alternation task at 3 to 24 months old. The results demonstrated a decrement in long-term working memory as early as 6 months in Rora(+)/Rora(+) mice and at 3 months in Rora(+)/Rora(sg) mice. Previous studies showed that in both cases, neuronal number in the cerebellar cortex was normal. This suggests that age-dependent decrease in long-term working memory would be due to fine structural or biochemical changes preceding neuronal death in the cerebellum. Such subtle changes would occur more precociously in Rora(+)/Rora(sg) than in Rora(+)/Rora(+) mice. Also, short-term working memory was preserved in Rora(+)/Rora(+) mice as old as 24 months, but was impaired in 6-month-old Rora(+)/Rora(sg) mice.


Maximum speed exposures in Australian rules football: do methods matter?
This study compared weekly near-to-maximum speed exposure data when determined via different methods and criteria. Forty-seven professional Australian rules football (AF) players undertook pre-season sprint assessments (PSSA) via 3 × 50 m maximal efforts using 10 Hz GPS over two consecutive seasons. The same technology was used continually during the in-season to identify maximum speeds attained in training and matches. Weekly near-to-maximal speed (MS) exposure counts were aggregated for speeds ≥80%, ≥85%, ≥90% and ≥95% of their individual maximum for both determination approaches. Weekly near-to-MS exposures was lower (p < 0.0001) when determined from in-season monitoring for ≥80% (-1.26; CI: -1.58 to -0.93), ≥85% (-0.78; CI: -0.97 to -0.59), ≥90% (-0.42; CI: -0.53 to -0.32), and ≥95% (-0.09; CI: -0.12 to -0.06) versus PSSA, with no effect of playing position (P ≥ 0.161). Although ≥80% and ≥85% near-to-maximum speed exposure data was meaningfully influenced by the determination method, the effect was somewhat trivial at higher speed criteria (≥90% and ≥95%) often considered important for performance gains and injury risk reduction purposes. Maximum speed determination methods therefore may be used interchangeably, and discrete sprint assessments may not be necessary for this purpose.


Comparison of protocols for DNA extraction from long-term preserved formalin fixed tissues.
The current study compared the applicability of protocols to extract DNA from formalin fixed heart tissues that have been preserved for more than 50 years. Ten methods were tested: a cetyltrimethylammonium bromide (CTAB) standard protocol, seven variants of this standard protocol, and two commercial kits. In the case of younger specimens (fixed in 1951, 1934, or 1914), extracts with DNA concentrations ≥ 10.0 ng/μl were obtained with the standard CTAB protocol, two variants of the standard protocol including prolonged tissue digestion (72 h instead of 1-2h), and a commercial kit particularly recommended for DNA extraction from formalin fixed paraffin embedded tissues (FFPE Kit). With the FFPE Kit, DNA could also be extracted from older tissues (fixed in 1893, 1850/1851, or before 1820). In general, the purity of the DNA extracts, assessed from the ratio of the absorbance at 260 and 280 nm, was not very high. In spite of their rather low purity, the DNA extracts could, however, be used to amplify a 122-bp sequence and, in most cases, also a 171-bp sequence of the gene coding for human albumin by the polymerase chain reaction (PCR).


The role of rumination in the guilt associated with bereavement according to cause of death.
The purpose of this study was to analyse the role rumination plays in the relationship between cause of death and the guilt present during bereavement. The sample consisted of 90 people that had suffered a loss due to an expected or unexpected natural death, suicide or accident. The results suggest that rumination increases the levels of guilt felt by people that had suffered a loss due to suicide compared to those whose loss was due to an expected natural death. These findings contribute to a better understanding of the mechanisms with an influence on bereavement.


Trichoscopy Tips.
Although trichoscopy has only recently been introduced in the assessment of hair and scalp disorders, it is already considered an essential diagnostic tool by many experts in the field. This article discusses topics that are often a source of doubt among clinicians, and tips that may help dermatologists better perform trichoscopy. Subjects include fundamental concepts needed to start performing the method, basic trichoscopic structures, tips to identify a scarring condition and to approach a patient with a receding hairline, features that are unique to children, those that are typically seen in the dark scalp, and pitfalls of the technique.


Case report of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography imaging of a patient with multiple endocrine gland metastases from small cell lung cancer.
Synchronous multiple endocrine gland metastasis caused by small cell lung cancer (SCLC) is rare. A patient was investigated for primary cancer because of suspected brain metastasis on computed tomography (CT). Baseline 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT was positive in the lung and multiple endocrine glands (right thyroid, right breast, pancreatic body, right adrenal gland, and left ovary). Histopathology confirmed small cell lung cancer. The patient's symptoms were alleviated after chemotherapy and brain radiotherapy. Follow-up PET-CT revealed that some of the lesions had disappeared and some had reduced in size. This rare case of multiple endocrine gland metastases from SCLC suggests that whole body PET-CT is a useful tool to detect rare/asymptomatic metastases.


Differential diagnosis of mesenchymal neoplasms of the digestive tract by cell block and immunohistochemistry.
To evaluate the diagnostic yield of the cell block (CB) technique with immunohistochemistry in patients with mesenchymal neoplasms of the gastrointestinal tract collected by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Tissue samples from consecutive patients with subepithelial lesions collected by EUS-FNA, without analysis by on-site cytopathology, were evaluated by the same pathologist only using CBs in AAF fixative. Sections were stained with haematoxylin-eosin and underwent complementary immunohistochemical staining for SMA, CD117, DOG-1 and S100 in the presence of mesenchymal neoplasms. Specimens were defined as diagnostic when sufficient tissue was present for histopathological evaluation and immunohistochemistry analysis. If they were insufficient for complete evaluation, the specimens were considered nondiagnostic. Between September 2012 and December 2016, a total of 158 patients (median age: 57 years, 64.5% women) underwent EUS-FNA with an average of three needle passes for every lesion. The median lesion size was 17 mm. There were 113 mesenchymal neoplasms confirmed by immunohistochemistry (66 leiomyomas, 44 GISTs, two schwannomas, one leiomyosarcoma). The overall diagnostic yield of CBs was 84.17%. However, diagnosis was obtained in 98.5% (133/135) of the cases after exclusion of 23 cases in which EUS-FNA sampling was insufficient or without tumoural tissue. Only two mesenchymal neoplasms were not confirmed by CBs even after immunohistochemistry. CBs collected by EUS-FNA and analysed by immunohistochemistry showed a high diagnostic yield in patients with mesenchymal neoplasms, even without on-site cytopathology.


Susceptibility of low density lipoprotein to oxidation in familial hypercholesterolaemia.
There is increasing evidence that oxidative modification of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis. Subjects with familial hypercholesterolaemia (FH) have elevated concentrations of LDL and develop premature atherosclerosis. The aim of the study was to determine whether the susceptibility of LDL to in vitro oxidation is increased in FH subjects. LDL was isolated from 15 FH homozygotes (mean age +/- SD, 19 +/- 10 years; mean LDL-cholesterol 16.86 +/- 3.55 mmol/l), 15 FH heterozygotes (38 +/- 13 years; LDL-cholesterol 5.58 +/- 1.78 mmol/l) and 15 normocholesterolaemic subjects (31 +/- 8 years; LDL-cholesterol 3.07 +/- 0.77 mmol/l). Susceptibility of LDL to in vitro copper-mediated oxidation was assessed by measuring conjugated diene production at 234 nm, the lag phase being a measure of the resistance of LDL to oxidation. Unexpectedly, the mean duration of the lag phase was 2.2 fold longer in the FH homozygotes (123.8 +/- 45.0 min) and 1.75-fold longer in the FH heterozygotes (99.9 +/- 40.6 min) than in the controls (57.1 +/- 27.9 min; P < 0.0001). Serum and LDL vitamin E levels were higher in the FH patient, but not when expressed relative to LDL-cholesterol concentration. There was also no correlation between LDL vitamin E concentration and duration of the lag phase. LDL bulk rather than the susceptibility of LDL to oxidation is probably the more important factor for the initiation and progression of atherosclerosis in FH patients.


Knowledge, attitudes, and behavior regarding antibiotics, antibiotic use, and antibiotic resistance in students and health care professionals of the district of Barranquilla (Colombia): A cross-sectional survey.
To evaluate the knowledge, attitudes and behavior regarding antibiotics, use of antibiotics, and antibiotic resistance in students and health care professionals of the district of Barranquilla, Colombia. Descriptive, cross-sectional. A sample of 399 respondents was selected, that included health professionals and medical students from 12 health institutions in the district of Barranquilla (Colombia), using an established stratified sampling method. Each of the respondent professionals completed a survey that included 43 items in the Likert scale. A descriptive analysis of the study variables was performed using the software SPSS version 25. Most of the respondents were women (64.4%), aged between 26 and 35 years (47.6%); 28.8% were nurses and 26.1% general practitioners, with ≤10 years of professional experience (63.4%). Overall, the survey revealed that the participants had considerable knowledge about antibiotic use (89.5%-98% correct answers) and the spread of antibiotic resistance (67.4%-89% correct answers). Approximately 74% of the respondents agreed or fully agreed with the questions related to the management of infections and the provision of advice. The present study revealed that most of the health care professionals surveyed had a good knowledge about antibiotic use, although strategies must be developed to strengthen knowledge regarding the spread of antibiotic resistance. Likewise, it is important to identify opportunities for improvement related with access to the guidelines and/or materials necessary to treat infections and to provide advice on antibiotic use and antibiotic resistance.


alpha-Methyl-p-tyrosine pretreatment partially prevents methamphetamine-induced endogenous neurotoxin formation.
Depletion of brain dopamine (DA) by pretreatment with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMT) has been shown to prevent the long-term neurotoxic effects of methamphetamine (MA). In addition, it has recently been reported that the neurotoxins 6-hydroxydopamine (6-OHDA) and 5,6-dihydroxytryptamine (5,6-DHT) are formed endogenously in neostriatum and hippocampus, respectively, following a single neurotoxic dose of MA. We, therefore, have examined the ability of AMT pretreatment to prevent the MA-induced formation of 6-OHDA and 5,6-DHT. We report that AMT pretreatment significantly decreases the frequency with which 6-OHDA and 5,6-DHT are detected following MA administration. Neurotoxin formation is compared with brain levels of DA and 5-hydroxytryptamine (5-HT) 2 weeks after MA administration. It is concluded that the ability of AMT to attenuate both 6-OHDA formation and long-term depletions of DA is due to a decrease in the MA-releasable pool of DA. The effect of AMT on MA-induced depletions of 5-HT is less clear and may involve additional factors.


Postoperative acute cholecystitis: a collective review of 494 cases in Japan.
The clinical course and management of 494 patients with postoperative acute cholecystitis, encountered at 122 hospitals in Japan during the last decade, were reviewed. The incidence of the disease from the total operations was 0.06 per cent, and 445 patients (90 per cent) were acalculous. The mean age of the patients was 60 years, and the ratio of male to female was 2.8:1. Total gastrectomy, subtotal gastrectomy, and esophagectomy were the most common operations precipitating postoperative acute cholecystitis. Vagotomy, dissection of the upper abdominal lymph nodes, and prolonged fasting were prevalent among the risk factors. Clinical diagnosis was confirmed in most patients by ultrasonography. Among the various treatments, cholecystectomy brought the lowest mortality rate; the overall mortality rate being 23 per cent. When this disease is suspected, ultrasonography should be performed repeatedly and percutaneous transhepatic gallbladder drainage or cholecystectomy are recommended as being the treatments of choice.


Unsuspected foreign body in the frontal sinus and anterior cranial fossa.
We present the case of a 46-year-old man who was involved in a motor vehicle accident in which his forehead struck the dashboard of his semi-tractor trailer. A toggle switch penetrated the anterior and posterior tables of his frontal sinus and lodged in the frontal lobe. The foreign body was not found on physical examination at an emergency care facility. The wound was closed, and the patient was sent home. Severe headaches prompted his return the next day. Skull roentgenograms showed the toggle switch, and the patient was referred to our institution for definitive care. This unusual case serves to emphasize the potential for a foreign body to penetrate the frontal sinus with few physical findings.


Inhibition of progesterone receptor activity in recombinant yeast by soot from fossil fuel combustion emissions and air particulate materials.
Numerous environmental pollutants have been detected for estrogenic activity by interacting with the estrogen receptor, but little information is available about their interactions with the progesterone receptor. In this study, emission samples generated by fossil fuel combustion (FFC) and air particulate material (APM) collected from an urban location near a traffic line in a big city of China were evaluated to interact with the human progesterone receptor (hPR) signaling pathway by examining their ability to interact with the activity of hPR expressed in yeast. The results showed that the soot of a petroleum-fired vehicle possessed the most potent anti-progesteronic activity, that of coal-fired stove and diesel fired agrimotor emissions took the second place, and soot samples of coal-fired heating work and electric power station had lesser progesterone inhibition activity. The anti-progesteronic activity of APM was between that of soot from petroleum-fired vehicle and soot from coal-fired establishments and diesel fired agrimotor. Since there was no other large pollution source near the APM sampling sites, the endocrine disrupters were most likely from vehicle emissions, tire attrition and house heating sources. The correlation analysis showed that a strong relationship existed between estrogenic activity and anti-progesteronic activity in emissions of fossil fuel combustion. The discoveries that some environmental pollutants with estrogenic activity can also inhibit hPR activity indicate that further studies are required to investigate potential mechanisms for the reported estrogenic activities of these pollutants.


The neural basis for shape preferences.
Several dimensions of shape, such as curvature or taper, can be regarded as extending from a singular (S) or 0 value (e.g., a straight contour with 0 curvature or parallel contours with a 0 angle of convergence) to an infinity of non-singular (NS) values (e.g., curves and non-parallel contours). As orientation in depth is varied, an S value remains S, and a NS value will vary but will remain NS. Infant and adult human participants viewed pairs of geons where one member had an S and the other had a NS value on a given shape dimension, e.g., a cylinder vs. a cone. Both adults and infants looked first, and adults looked longer at the NS geons. The NS geons also produced greater fMRI activation in shape selective cortex (LOC), a result consistent with the greater single unit activity in macaque IT produced by those geons (Kayaert et al., 2005). That NS stimuli elicit higher neural activity and attract eye movements may account for search asymmetries in that these stimuli pop out from their S distractors but not the reverse. A positive association between greater activation in higher-level areas of the ventral pathway and visual preference has been demonstrated previously for real world scenes (Yue, Vessel, & Biederman, 2007) and may reflect the workings of a motivational system that leads humans to seek novel but richly interpretable information.


Aging-induced impaired endothelial wall shear stress mechanosensing causes arterial remodeling via JAM-A/F11R shedding by ADAM17.
Physiological and pathological vascular remodeling is uniquely driven by mechanical forces from blood flow in which wall shear stress (WSS) mechanosensing by the vascular endothelium plays a pivotal role. This study aimed to determine the novel role for a disintegrin and metalloproteinase 17 (ADAM17) in impaired WSS mechanosensing, which was hypothesized to contribute to aging-associated abnormal vascular remodeling. Without changes in arterial blood pressure and blood flow rate, skeletal muscle resistance arteries of aged mice (30-month-old vs. 12-week-old) exhibited impaired WSS mechanosensing and displayed inward hypertrophic arterial remodeling. These vascular changes were recapitulated by in vivo confined, AAV9-mediated overexpression of ADAM17 in the resistance arteries of young mice. An aging-related increase in ADAM17 expression reduced the endothelial junction level of its cleavage substrate, junctional adhesion molecule-A/F11 receptor (JAM-A/F11R). In cultured endothelial cells subjected to steady WSS ADAM17 activation or JAM-A/F11R knockdown inhibited WSS mechanosensing. The ADAM17-activation induced, impaired WSS mechanosensing was normalized by overexpression of ADAM17 cleavage resistant, mutated JAM-AV232Y both in cultured endothelial cells and in resistance arteries of aged mice, in vivo. These data demonstrate a novel role for ADAM17 in JAM-A/F11R cleavage-mediated impaired endothelial WSS mechanosensing and subsequently developed abnormal arterial remodeling in aging. ADAM17 could prove to be a key regulator of WSS mechanosensing, whereby it can also play a role in pathological vascular remodeling in diseases.


Threshold of equinus which alters biomechanical gait parameters in children.
The main aim of this study was to define the threshold angle of equinus beyond which significant changes in 3D lower limb kinematics and kinetics occur in typically developing children and to describe these changes.A customized orthosis was fitted on the right ankle of 10 typically developing children and was adjusted to +10° ankle dorsiflexion, 0°, -10°, -20° plantarflexion and maximum plantarflexion. Gait was analyzed using an optoelectronic system. A gait velocity of 1m/s was imposed.Most of the kinematic and kinetic changes were significantly altered from the -10° condition. In the sagittal plane, the results showed increased knee flexion at initial contact, increased knee flexion or hyperextension in stance, increased hip flexion at initial contact and increased anterior pelvic tilt. Other changes included increased knee varus, reduced hip adduction and more internal foot progression. The ankle plantarflexion moment was bi-phasic during stance, peak ankle power generation was reduced, peak knee extension moment was decreased and hip extension moments increased. On the contralateral side, there was a significant increase in ankle plantarflexion at initial contact and a significant decrease in knee flexion during swing phaseat maximum plantarflexion.Although slight modifications occurred for smaller degrees of equinus, the results suggest that significant kinematic and kinetic changes occurred during gait in both limbs from 10° of plantarflexion. The results of this study also provide some indications regarding the primary causes of gait deviations and secondary compensatory strategiesin children with a clinical dorsiflexion limitation.


Intrahepatic and portal venous gas detected by ultrasonography.
During a 3-year period, sonographic evidence of portal venous gas (PVG) was found in 11 patients. Of these, 10 patients were examined for clinically suspected necrotizing enterocolitis (NEC). In the 11th patient, suffering from nephroblastoma, PVG was detected by routine sonography. Radiographic examination, performed in nine of 11 patients did not show any PVG. Intestinal pneumatosis was radiographically identifiable in only four of these children, whereas eight of 11 patients with sonographically detectable PVG also had sonographic evidence of intramural gas. Follow-up examinations in five patients showed cessation of PVG soon after onset of adequate therapy, indicating that ultrasonography is also a reliable method for monitoring NEC. Sonographic evidence of PVG, however, may be limited to the time before onset of therapy.


Confocal laser scanning microscopic investigation of ultrasonic, sonic, and rotary sealer placement techniques.
Sealers are used to attain an impervious seal between the core material and root canal walls. To compare the depth and percentage of sealer penetration with three different placement techniques using confocal laser scanning microscopy as the evaluative tool. Root canals of 30 single-rooted teeth were prepared to a size of F3 and AH plus sealer with Rhodamine B was applied with Ultlrasonic file (Gr-1), lentulospiral (Gr-2), and Endoactivator (Gr-3). Canals were obturated with gutta-percha. The roots were sectioned at the 3 and 6-mm levels from the apical foramen and were examined on a confocal microscope. A statistical significant differences among Gr-1, Gr-2, and Gr-3 were found at the 3 and 6-mm level (P < 0.05; ANOVA-Tukey tests) for the depth and percentage of sealer penetration except for Gr-1 and Gr-2 at 3-mm level. Gr-1 showed maximum mean depth of penetration (810 μm) and maximum mean percentage of sealer penetration (64.5) while Gr-3 showed minimum mean depth of penetration (112.7 μm) and minimum mean percentage of sealer penetration (26.7). Depth and percentage of penetration of sealer is influenced by the type of placement technique and by the root canal level with penetration decreasing apically.


Metagenomic sequencing for identifying pathogen-specific circulating DNAs and development of diagnostic methods for schistosomiasis.
Timely diagnosis of Schistosoma infection, particularly in the early stage is crucial for identifying infected hosts and then taking effective control strategies. Here, metagenomic next-generation sequencing was used to identify pathogen-specific circulating DNAs (cDNAs) in the sera/plasma of New Zealand rabbits infected with S. japonicum, and the identified cDNAs were validated by PCR and qPCR. Loop-mediated isothermal amplification (LAMP)-based CRISPR-Cas12a and recombinase polymerase amplification-based lateral flow strip (RPA-LF) methods combined with the newly identified cDNA were developed to evaluate the potentials for diagnosing murine and human schistosomiasis. The results indicated that twenty-two cDNAs were identified. The developed LAMP-based CRISPR/Cas12a and RPA-LF methods showed a good potential for diagnosing murine or human schistosomiasis as early as 5 days of post-infection with 5 cercariae infection. In a word, S. japonicum specific cDNAs in circulation of infected hosts could be effective biomarkers for detecting Schistosoma infection particularly for early stages.


Do foraging bumblebees scent-mark food sources and does it matter?
The foraging of worker bees of Bombus terrestris visiting artificial feeders in a climatic test chamber was investigated. The behaviour of worker bees visiting rewarding and unrewarding feeders is completely different. Of all flower visits to rewarding feeders 94% are probing-visits, i.e. the bees land on the flower and probe for nectar. In contrast, only 0.3% of all visits to unrewarding feeders are probing-visits, whereas 47% are approach-visits, i.e., the bees approach the feeders without landing. Exchanging feeder discs proves that the signal used for discrimination must be associated with the plastic disc used as landing platform. Most probably it involves scent-marking of the rewarding feeders with components of high and low volatility. The mean foraging efficiency of bees in a scent-marked foraging arena is 5.7 mg sugar/min and drops to 2.8 mg sugar/min after the scent marked discs are replaced by clean ones. Three components generate this drop in foraging efficiency: (1) the between-flower flight time increases, i.e. the bees search for a longer time before landing on flowers, (2) the bees no longer discriminate between rewarding and unrewarding feeders, and (3) the bees probe empty feeders longer than necessary; obviously they expect to find nectar.


Ketamine suppresses endotoxin-induced NF-kappaB activation and cytokines production in the intestine.
Ketamine has been advocated for anesthesia in endotoxemic and other severely ill patients because it is a cardiovascular stimulant. However, ketamine also suppresses serum levels of endotoxin-induced tumor necrosis factor-alpha, and reduces mortality in mice in endotoxin shock. Our study was designed to investigate the protective effect of ketamine on the endotoxin-induced proinflammatory cytokines and nuclear factor kappa B (NF-kappaB) activation in vivo. Adult male Wistar rats were randomly divided into six groups: saline controls; rats challenged with endotoxin (5 mg kg(-1)) and treated with saline; challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (0.5 mg kg(-1)); challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (5 mg kg(-1)); challenged with endotoxin (5 mg kg(-1)) and treated with ketamine (50 mg kg(-1)); and saline injected and treated with ketamine (50 mg kg(-1)). TNF-alpha, IL-6 and NF-kappaB were investigated in the tissues of the intestine (jejunum) after 1, 4 and 6 h. Endotoxin caused transient production of TNF-alpha and IL-6 and activation of NF-kappaB in the intestine at peak times of 1, 4 and 1 h, respectively. Ketamine 0.5 mg kg(-1) suppressed endotoxin-induced TNF-alpha elevation and inhibited NF-kappaB activation in the intestine; a dose of 5 mg kg(-1) was required to inhibit IL-6. Ketamine suppresses the production of proinflammatory cytokines such as TNF-alpha and IL-6 in the intestine, possibly via inhibition of NF-kappaB.


Polymeric micelles with a pH-responsive structure as intracellular drug carriers.
Polymeric micelles based on poly(L-lactide)-b-poly(2-ethyl-2-oxazoline)-b-poly(L-lactide) (PLLA-PEOz-PLLA) ABA triblock copolymers were designed as intracellular drug carriers. The PLLA-PEOz-PLLA micelles adopt a "flower-like" arrangement with A-blocks at the core and a B-block on the shell under neutral condition. The deformation of the core-shell structure is then promoted by the aggregation of PEOzs due to the formation of inter- and intra-hydrogen bonding between protonated nitrogen and carbonyl groups. The experiments on in vitro release have confirmed that the release of doxorubicin (DOX) from micelles was successfully inhibited at pH 7.4. In contrast, an accelerated release of DOX from micelles was observed at acidic conditions. The results of growth inhibition assay indicated that the cell-killing rate of DOX-loaded micelles gradually approached that of free DOX as increasing the concentration and the incubation time. The overlay of fluorescent images on CLSM observation clearly demonstrated the colocalization of DOX with acidic compartments, suggesting that the drug release was successfully triggered in the acidic organelles by means of micelle deformation.


Cell Models to Study Cell-to-Cell Transmission of α-Synuclein.
The cell-to-cell transmission of protein aggregates has been implicated in the progression of pathological phenotypes in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In recent years, several experimental model systems have been developed to study the mechanisms of cell-to-cell transmission. Herein, we describe cell culture models with which cell-to-cell transmission of α-synuclein can be quantitatively analyzed. The principle underlying these models could be applied to developing model systems for transmission of other protein aggregates, such as tau and TDP-43.


STIM1 is required for attenuation of PMCA-mediated Ca2+ clearance during T-cell activation.
T-cell activation involves a complex signalling cascade uniquely dependent on elevated cytosolic Ca(2+) levels. Further, the spatiotemporal characteristics of this Ca(2+) signal play a critical role in this process via selective activation of transcription factors. In T cells, store-operated Ca(2+) entry (SOCe) is the primary Ca(2+) influx pathway; however, cytosolic Ca(2+) concentration depends upon the balance between Ca(2+) influx and extrusion. The plasma membrane Ca(2+) ATPase (PMCA) has previously been identified as a critical player in Ca(2+) clearance in T cells. Here, we provide data revealing both functional and physical links between the activation of stromal interacting molecule 1 (STIM1) and PMCA-mediated Ca(2+) clearance. Due to the ubiquitous expression of both STIM1 and PMCA, these findings have wide-ranging implications for Ca(2+) signalling in multiple cell types.


The relationship of the erythrocyte sedimentation rate to inflammatory cytokines and survival in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors.
The object of the study was to assess the relationship between erythrocyte sedimentation rate (ESR) and inflammatory cytokine production in chronic heart failure (CHF). Our findings lead us to re-evaluate the prognostic value of the ESR in assessing patients with CHF. The search for simple prognostic markers in CHF that can be assessed anywhere at low cost is important. Increases in ESR are related to the acute phase response in states of inflammation and infection. Initially, we studied ESR in relation to plasma levels of inflammatory cytokines in 58 CHF patients. The findings prompted us to analyze the mortality predictive power of ESR compared with established risk factors in these patients and (retrospectively) in a second group of 101 clinically stable CHF patients who had ESR measured. In all 159 CHF patients (age 62+/-2 years, New York Heart Association [NYHA] class 2.7+/-0.1), ESR ranged from 1 to 96 mm/h (median 14 mm/h). The ESR was correlated with tumor necrosis factor (TNF)-alpha (r = 0.31, p<0.05), soluble TNF receptor-1 (r = 0.48, p<0.0005), soluble TNF receptor-2 (r = 0.39, p<0.005) and interleukin 6 (r = 0.45, p<0.005) levels. High ESR levels indicated a poor prognosis (p<0.0001), and this was independent of age, NYHA class, ejection fraction and peak oxygen consumption (p < 0.005). Patients with ESR above median (> or =15 mm/h) compared with patients with ESR <15 mm/h had an impaired survival (hazard ratio 2.62, 95% confidence interval 1.58-4.36, p<0.0001). Our study demonstrates that in CHF a high ESR is an unfavorable prognostic sign, independent of patients' symptomatology and ventricular function. These results are in diametrical contrast to previous results. This may reflect a change in the underlying pathophysiology due to today's treatment with angiotensin-converting enzyme inhibitors.


Pediatric nursing resources in cyberspace.
To provide information on pediatric nursing resources on the Internet. Pediatric nurses in all settings. A basic understanding of essentials for "surfing the web" will open the doors to unprecedented opportunities to query, find, and share information with others. Pediatric nurses in every setting can benefit from access to the Internet and knowledge of what resources are available to enhance their practice and support their clients.


Correlates of Lifetime History of Purchasing Sex Services by Men in Saint Petersburg and Leningrad Oblast, Russia.
Commercial sex workers (CSWs) in the Russian Federation are at high risk of HIV infection and transmission as a result of unsafe sexual and injecting behaviors. Their clients might be at increased risk of acquiring HIV; however, little is known about the population of men purchasing sex services. This study aims to investigate factors associated with a history of purchasing sex services by men in Saint Petersburg and Leningrad Oblast, Russian Federation. Data were collected as part of a cross-sectional study offering free anonymous rapid HIV testing in Saint Petersburg and Leningrad Oblast in 2014; in total, 3565 men aged 18 years and older provided information about their behaviors associated with risk of acquiring HIV during face-to-face interviews. Prevalence of CSW use in our study was 23.9%. Multivariable analyses using log-binomial regression were stratified by self-reported HIV testing during the 12 months preceding the study interview. In both strata, older age, multiple sex partners, and a history of sex with an injection drug user (IDU) were associated with an elevated prevalence ratio (PR) for history of purchasing sex services, although the strength of the association differed by strata. Among men who reported recent HIV testing, condom use (PR = 1.22, 90% confidence interval (CI) 1.0, 1.48) was associated with a history of purchasing sex services, and among men who did not report recent HIV testing, having a consistent sex partner was associated with purchasing sex services (PR = 1.23, 90% CI 1.1, 1.37). The high prevalence of CSW service use and associations found in this study raise serious concerns about potential for sexual HIV transmission and should be investigated more closely.


The activity of two heat shock loci of Drosophila hydei in tissue culture cells and salivary gland cells as analyzed by in situ hybridization of complementary DNA.
Complementary DNA was made to poly A+ nuclear or polysomal RNA isolated from heat shock tissue culture cells of Drosophila hydei. A number of loci other than the four major heat shock loci are labelled after in situ hybridization of these cDNA preparations, while solution hybridization indicated that only about 10% of the cDNA was specific for heat shocked cells. Removal of the fraction of cDNA which could react with 25 degrees C RNA and subsequent in situ hybridization of heat shock specific cDNA indicated that locus 4-81 B, a major salivary gland heat shock locus, is also active at 25 degrees C in tissue culture cells, while locus 4-85 B is specifically activated by heat shock in tissue culture cells. This latter locus is not seen to be clearly puffed in salivary glands, but was shown to be active in that tissue both by direct autoradiography of salivary gland chromosomes after 3H-uridine labeling and by hybridization of cDNA to chromosomal RNA.


Laterality of arm movement in full-term newborn.
We have investigated 20 healthy full-term newborns between the 4th and the 6th day of life in standard conditions for laterality of arm movements, before and after introduction of a target. The durations of recording were: (a) 5 min continuously before target introduction; (b) five 1-min units during target presentation. The movements studied were extension, flexion, movement with semiflexed arm with hand half-open or open toward the midline of the body, and total movements. Each of these items were counted separately and the counts were compared within and between sides. Spontaneous movements showed no side preference whereas in the presence of the target, movements toward the midline (target directed movements) showed a significant right-hand preference.


Gifa V. 4: A complete package for NMR data set processing.
The Gifa program is designed for processing, displaying and analysing 1D, 2D and 3D NMR data sets. It has been constructed in a modular fashion, based on three independent modules: a set of commands that perform all the basic processing operations such as apodisation functions, a complete set of Fourier Transforms, phasing and baseline correction, peak-picking and line fitting, linear prediction and maximum entropy processing; a set of command language primitives that permit the execution of complex macro commands; and a set of graphic commands that permit to build a complete graphic user interface, allowing the user to interact easily with the program. We have tried to create a versatile program that can be easily extended according to the user's requirements and that is adapted to a novice as well as an experienced user. The program runs on any UNIX computer, with or without graphic display, in interactive or batch mode.


Observed sensitivities of PM2.5 and O3 extremes to meteorological conditions in China and implications for the future.
Frequent extreme air pollution episodes in China accompanied with high concentrations of particulate matters (PM2.5) and ozone (O3) are partly supported by meteorological conditions. However, the relationships between meteorological variables and pollution extremes can be poorly estimated solely based on mean pollutant level. In this study, we use quantile regression to investigate meteorological sensitivities of PM2.5 and O3 extremes, benefiting from nationwide observations of air pollutants over 2013-2019 in China. Results show that surface winds and humidity are identified as key drivers for high PM2.5 events during both summer and winter, with greater sensitivities at higher percentiles. Higher humidity favors the hydroscopic growth of particles during winter, but it tends to decrease PM2.5 through wet scavenging during summer. Surface temperature play dominant role in summer O3 extremes, especially in VOC-limited regime, followed by surface winds and radiation. Sensitivities of O3 to meteorological conditions are relatively unchanging across percentiles. Under the fossil-fueled development pathway (SSP5-8.5) scenario, meteorological conditions are projected to favor winter PM2.5 extremes in North China Plain (NCP), Yangtze River Delta (YRD) and Sichuan Basin (SCB), mainly due to enhanced surface specific humidity. Summer O3 extremes are likely to occur more frequently in the NCP and YRD, associated with warmer temperature and stronger solar radiation. Besides, meteorological conditions over a relatively longer period play a more important role in the formation of pollution extremes. These results improve our understanding of the relationships between extreme PM2.5 and O3 pollution and meteorology, and can be used as a valuable reference of model predicted air pollution extremes.


On the pathogenesis of mitochondrial myopathies. An experimental study.
The intra-arterial injection of 2-4 dinitrophenol, an uncoupler of oxidative phosphorylation, resulted in the production of ragged red fibers. The ultrastructure of these fibers showed intramitochondrial paracrystalline inclusions, laminar and fingerprint bodies. Antimycin A and oligomycin injection (which inhibit mitochondrial respiration) only caused swelling and disruption of the mitochondria. An increase in muscle lactic acid, decrease in ATP, glycogen and phosphocreatine was observed after the injection of all these agents. This indicates that lactic acidosis has no significant role in the pathogenesis of mitochondrial pathology. It is concluded that mitochondrial changes are a morphological expression of uncoupled but intact mitochondrial respiration.