Elevated Polygenic Burden for Autism Spectrum Disorder Is Associated With the Broad Autism Phenotype in Mothers of Individuals With Autism Spectrum Disorder.
Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder that encompasses a complex and heterogeneous set of traits. Subclinical traits that mirror the core features of ASD, referred to as the broad autism phenotype (BAP), have been documented repeatedly in unaffected relatives and are believed to reflect underlying genetic liability to ASD. The BAP may help inform the etiology of ASD by allowing the stratification of families into more phenotypically and etiologically homogeneous subgroups. This study explores polygenic scores related to the BAP. Phenotypic and genotypic information were obtained from 2614 trios from the Simons Simplex Collection. Polygenic scores of ASD (ASD-PGSs) were generated across the sample to determine the shared genetic overlap between the BAP and ASD. Maternal and paternal ASD-PGSs were explored in relation to BAP traits and their child's ASD symptomatology. Maternal pragmatic language was related to child's social communicative atypicalities. In fathers, rigid personality was related to increased repetitive behaviors in children. Maternal (but not paternal) ASD-PGSs were related to the pragmatic language and rigid BAP domains. Associations emerged between parent and child phenotypes, with more associations emerging in mothers than in fathers. ASD-PGS associations emerged with BAP in mothers only, highlighting the potential for a female protective factor, and implicating the polygenic etiology of ASD-related phenotypes in the BAP.


Does the overvaluation of shape and weight predict initial symptom severity or treatment outcome among patients with binge eating disorder?
To examine whether overvaluation of shape and weight is associated with initial symptom severity or treatment outcome among patients with binge eating disorder (BED). Patients with BED (n = 116) completed assessments at baseline and treatment termination, including the Eating Disorder Examination (EDE) and self-report measures of eating-related cognitions and behaviors, depression, and self-esteem. Clinical overvaluation was determined by EDE. The clinical overvaluation group demonstrated significantly higher pre-treatment scores on measures of depression, behavioral and cognitive aspects of binge eating, and eating-related psychopathology, and lower self-esteem scores than individuals without overvaluation. At treatment termination, patients with overvaluation continued to display elevated scores on measures of binge eating severity at a trend level. Overvaluation of shape and weight was associated with symptom severity in patients with BED, but additional research is needed to determine whether this construct holds clinically useful predictive validity for treatment outcome.


Wandering hemi-spleen: Laparoscopic management of wandering spleen in a case of polysplenia.
Several congenital anomalies of the spleen have been reported. The polysplenia is a rare anomaly in which the normal spleen is replaced with two or more smaller spleens. The wandering spleen is another anomaly resulting from the laxity of the splenic ligaments. The concomitance of both anomalies is very rare. A 22-year old female patient presented with intermittent left hypochondrial pain for more than a year. After a thorough examination of the patient, she only had bilateral accessory nipples. Routine laboratory investigations were all normal. An abdominal ultrasound U/S scan was unremarkable except for a ptotic spleen. with a large splenule 5cm×3cm located near the fundus of the stomach. These findings were confirmed by a CT scan. A decision for a surgical intervention was then made, and the laparoscopic approach was chosen which revealed the condition. Laparoscopic removal of the wandering part was executed. The patient discharged on the first post-operative day. The decision making in cases of wandering spleen is not always the same. The association of a wandering spleen with polysplenia is an asset to the surgical decision, along with the age of the patient. The laparoscopic approach is an important tool in the diagnosis and management of wandering spleen. The diagnosis of polysplenic anomaly could provide a guidance for the surgical strategy in patients with wandering spleen.


Evaluating the possibility of uterine transfer by ultrasonically guided transabdominal puncture.
Ultrasonically guided transvesical puncture of the uterine endometrial cavity was carried out in 16 patients to evaluate the feasibility of embryo transfer by this procedure. Instillation of fluid into the uterine cavity was achieved in all cases and easily performed in 15 patients. In one patient the fundal endometrium was reached in the third attempt. Instillation of fluid within the endometrium was attempted unsuccessfully in four patients, as the fluid leaked into the uterine cavity. In 12 patients 2-4 ml of fluid was injected. The fluid passed down through the cervix in patients in the luteal phase (nine patients) when 3 ml or more was injected. When a smaller amount of fluid was instilled it remained inside the cavity. In one patient in the preovulatory phase the fluid was actively pumped by uterine contractions into the vagina. Two cases in the proliferative phase showed no leakage from the cervix when 1.5 and 2 ml of fluid was injected, respectively.


Single-cell transcriptomics reveals prominent expression of IL-14, IL-18, and IL-32 in psoriasis.
Psoriasis is a chronic inflammatory skin disease involving different cytokines and chemokines. Here we use single-cell transcriptomic analyses to identify relevant immune cell and nonimmune cell populations for an in-depth characterization of cell types and inflammatory mediators in this disease. Psoriasis skin lesions of eight patients are analyzed using single-cell technology. Data are further validated by in situ hybridization (ISH) of human tissues, serum analyses of human samples and tissues of a murine model of psoriasis, and by in vitro cell culture experiments. Several different immune-activated cell types with particular cytokine patterns are identified such as keratinocytes, T-helper cells, dendritic cells, macrophages, and fibroblasts. Apart from well-known factors, IL-14 (TXLNA), IL-18, and IL-32 are identified with prominent expression in individual cell types in psoriasis. The percentage of inflammatory cellular subtypes expressing IL-14, IL-18, and IL-32 was significantly higher in psoriatic skin compared with healthy control skin. These findings were confirmed by ISH of human skin samples, in a murine model of psoriasis, in human serum samples, and in in vitro experiments. Taken together, we provide a differentiated view of psoriasis immune-cell phenotypes that support the role of IL-14, IL-18, and IL-32 in psoriasis pathogenesis.


Pulmonary Capillary Hemorrhage Induced by Fixed-Beam Pulsed Ultrasound.
The induction of pulmonary capillary hemorrhage (PCH) by pulsed ultrasound was discovered 25 y ago, but early research used fixed-beam systems rather than actual diagnostic ultrasound machines. In this study, results of exposure of rats to fixed-beam focused ultrasound for 5 min at 1.5 and 7.5 MHz were compared with recent research on diagnostic ultrasound. One exposure condition at each frequency used 10-μs pulses delivered at 25-ms intervals. Three conditions involved Gaussian modulation of the pulse amplitudes at 25-ms intervals to simulate diagnostic scanning: 7.5 MHz with 0.3- and 1.5-μs pulses at 100- and 500-μs pulse repetition periods, respectively, and 1.5 MHz with 1.7-μs pulses at 500-μs repetition periods. Four groups were tested for each condition to assess PCH areas at different exposure levels and to determine occurrence thresholds. The conditions with identical pulse timing resulted in smaller PCH areas for the smaller 7.5-MHz beam, but both had thresholds of 0.69-0.75 MPa in situ peak rarefactional pressure amplitude. The Gaussian modulation conditions for both 7.5 MHz with 0.3-μs pulses and 1.5 MHz with 1.7-μs pulses had thresholds of 1.12-1.20 MPa peak rarefactional pressure amplitude, although the relatively long 1.5-μs pulses at 7.5 MHz yielded a threshold of 0.75 MPa. The fixed-beam pulsed ultrasound exposures produced lower thresholds than diagnostic ultrasound. There was no clear tendency for thresholds to increase with increasing ultrasonic frequency when pulse timing conditions were similar.


Are scoring systems sufficient for predicting mortality due to sepsis in the emergency department?
Scoring systems have been used to risk stratify in intensive care units (ICU), but not routinely used in emergency departments. The aim of this study was to determine accuracy for predicting mortality in emergency medicine with Sequential Organ Failure Assessment (SOFA), Mortality in ED Sepsis (MEDS) score and Simplified Acute Physiology Score (SAPSII). This is a prospective observational study. Patients presenting with evidence of sepsis were all included. SAPSII, MEDS, and SOFA scores were calculated. Analysis compared areas under the receiver operator characteristic (ROC) curves for 28-day mortality. Two hundred patients were included; consisting of 31 (14.3%) septic shock. 138 (69%) severe sepsis and 31 (15.5%) infection without organ dysfunction. 53 (26.5%) patients died within 28 days. Area under the ROC curve for mortality was 0.76 for MEDS (0.69-0.82), 0.70 for SAPSII (0.62-0.78); and 1.68 for SOFA (0.60-0.76) scores. Pair wise comparison of AUC between MEDS, SAPSII, SOFA and Lactate were not significant. According to our results; SOFA, SAPSII and MEDS were not sufficient to predict mortality. Also this result, MEDS was better than other scoring system.


Radiographic determination of total lung capacity in patients with acromegaly.
Total lung capacity (TLC) was measured from posteroanterior and lateral chest radiographs by the ellipsoid (TLCE) and planimetric (TLCp) radiographic methods in 16 acromegalic patients. These measurements were compared to the TLC measured by body plethysmography (TLCBP) in order to investigate the accuracy of the two radiographic methods. Our results showed that the mean value of TLCBP was 6.52 +/- 1.51 litres (mean +/- SD) or 120 +/- 13.3% of predicted values, statistically significantly increased from normal values (P less than 0.001). The mean value of TLCE was 7.09 +/- 1.8 litres and did not differ from the mean value of TLCBP (P greater than 0.125). The mean value of TLCP was 7.74 +/- 1.20 litres, statistically significantly increased from TLCBP (P less than 0.005). A statistically highly significant linear relationship was found between TLCE and TLCBP (r = 0.867, P less than 0.001) identical to the line of identity. Similarly a highly significant linear relationship was found between TLCP and TLCBP (r = 0.793, P less than 0.001) but to the left of the line of identity. It is concluded that both the ellipsoid and planimetric radiographic methods could be used to measure TLC in acromegalic patients but the planimetric method needed the appropriate correction.


Investigation on damage of DNA molecules under irradiation of low frequency ultrasound in the presence of hematoporphyrin-gallium (HP-Ga) complex.
The interaction of deoxyribonucleic acid (DNA) and hematoporphyrin-gallium (HP-Ga) complex and the damage of DNA under ultrasonic irradiation in the presence of HP-Ga complex were studied by means of UV-vis spectrum, fluorescence spectrum and gelatin electrophoresis. In addition, some influence factors such as ultrasonic irradiation time, HP-Ga complex concentration, ionic strength and solution acidity on the damage of DNA were also considered. Under a certain condition, the damage degree of DNA was enhanced with increasing ultrasonic irradiation time, HP-Ga complex concentration and ionic strength. Whether the pH value was too high or too low, it would be disadvantage to the damage of DNA. Perhaps, these results would be significant for driving sonodynamic treatment (SDT) to the clinic application in the future.


Alterations in signal transducing molecule CD3 zeta in patients with neoplastic diseases.
The impairment of immune cell functions in cancer patients may result from impairment of signal transduction. Recent studies have demonstrated altered expression and function of signal transduction molecule CD3 zeta in T and natural killer cells in patients with neoplastic diseases. Tumor infiltrating lymphocytes are more affected than peripheral blood lymphocytes. CD3 zeta expression is more prominent in advanced stage of the disease and correlates with reduced proliferative response, IFN-gamma, IL-2, TNF-alpha production.


The early bird catches the worm: new technologies for the Caenorhabditis elegans toolkit.
The inherent simplicity of Caenorhabditis elegans and its extensive genetic toolkit make it ideal for studying complex biological processes. Recent developments further increase the usefulness of the worm, including new methods for: altering gene expression, altering physiology using optogenetics, manipulating large numbers of worms, automating laborious processes and processing high-resolution images. These developments both enhance the worm as a model for studying processes such as development and ageing and make it an attractive model in areas such as neurobiology and behaviour.


The Practice of Cystoscopy with Hydrodistention Since the 2011 American Urological Association Clinical Guideline on Interstitial Cystitis/Bladder Pain Syndrome.
We determined the rate of cystoscopy with hydrodistention (CH) before and after the 2011 American Urological Association (AUA) amended clinical guideline, "Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome." Clinical encounters with a diagnosis of interstitial cystitis/bladder pain syndrome (IC/BPS) where cystoscopy with and without hydrodistention was performed were identified in the Vizient® Clinical Data Base between January 2009 and February 2020. Demographic and clinical information such as patient age, gender, race, treating physician specialty, insurance type and type of hospital (teaching vs nonteaching) was recorded. Descriptive statistics, Wilcoxon 2-sample test and chi-square test were used to compare variables. An interrupted time series analysis was used to assess the change in CH rate following the June 2011 AUA guideline. From January 2009 to February 2020, 69,983 encounters were identified to have an IC/BPS diagnosis and to have undergone outpatient cystoscopy, of which 7,502 (10.7%) were CH. Compared to those not undergoing CH, subjects with IC/BPS undergoing CH were younger, predominantly female, Caucasian and had commercial insurance. Before the guideline, across all medical specialties, the base rate of CH was rising from 16.6% at a rate of 0.12% per month. Following guideline release, the CH rate dropped by 6.8%, declining 0.07% per month until February 2020. This pattern was most pronounced in urology relative to all other medical specialties. The monthly average rate of CH among individuals with IC/BPS undergoing an outpatient CH dropped from nearly 17% before the 2011 AUA guideline to less than 10% in early 2020.


Preimplantation-stage stem cells induce long-term allogeneic graft acceptance without supplementary host conditioning.
Hematopoietic stem cells have been successfully employed for tolerance induction in a variety of rodent and large animal studies. However, clinical transplantation of fully allogeneic bone marrow or blood-borne stem cells is still associated with major obstacles, such as graft-versus-host disease or cytoreductive conditioning-related toxicity. Here we show that when rat embryonic stem cell-like cells of WKY origin are injected intraportally into fully MHC-mismatched DA rats, they engraft permanently (>150 days) without supplementary host conditioning. This deviation of a potentially alloreactive immune response sets the basis for long-term graft acceptance of second-set transplanted WKY cardiac allografts. Graft survival was strictly correlated with a state of mixed chimerism, which required functional thymic host competence. Our results provide a rationale for using preimplantation-stage stem cells as vehicles in gene therapy and for the induction of long-term graft acceptance.


Elevated estradiol levels in frozen embryo transfer have different effects on pregnancy outcomes depending on the stage of transferred embryos.
Supplementation with estradiol (E2) is routinely used in frozen embryo transfer (FET) cycles and embryo age plays an important role in conceiving. This study was to compare the effects of serum E2 levels on pregnancy outcomes between cleavage- and blastocyst-stage FET cycles using hormone replacement therapy. A total of 776 FET cycles (669 couples) performed from January 2016 to December 2019 were included in the present retrospective cohort study. Regarding cleavage-stage embryo transfers, E2 levels on progesterone initiation day were significantly lower in the ongoing pregnancy/live birth (OP/LB) group than in the non-OP/LB group (214.75 ± 173.47 vs. 253.20 ± 203.30 pg/ml; P = 0.023). In addition, there were downward trends in implantation, clinical pregnancy and OP/LB rates with increasing E2 levels. However, in blastocyst-stage embryo transfers, such trends were not observed, and E2 levels were not significant difference between the OP/LB group and the non-OP/LB group (201.66 ± 182.14 vs. 197.89 ± 212.83 pg/ml; P = 0.884). The results suggests that elevated progesterone-initiation-day E2 levels may negatively affect pregnancy outcomes during artificial cleavage-stage embryo transfers. However, it is not necessary to monitor E2 levels when transferring blastocysts in artificial FET cycles.


Molecular basis of death effector domain chain assembly and its role in caspase-8 activation.
Assembly of a death-inducing signaling complex is a key event in the extrinsic apoptotic pathway, enabling activation of the caspase cascade and subsequent cell death. However, the molecular events governing DISC assembly have remained largely elusive because of the lack of information on mechanism and specificity regulating the death effector domain (DED)-DED interaction network. Using molecular modeling, mutagenesis, and biochemical and ex vivo experiments, we identified the precise binding interface and hot spots crucial for intermolecular DED chain assembly. Mutation of key interface residues (Leu42/Phe45) in procaspase-8 DED-A completely abrogated DED chain formation in HEK293 cells and prevented its association with FADD. A significant 2.6-3.6-fold reduction in procaspase-8 activation was observed in functional cell-death assays after substitution of the interfacial residues. Based on our results we propose a new model for DISC formation that refines the current understanding of the activation mechanism. Upon stimulation, FADD self-associates weakly via reciprocal interaction between helices α1/α4 and α2/α3 of the DED to form an oligomeric signaling platform that provides a stage for the initial recruitment of procaspase-8 through direct interaction with α1/α4 of DED-A, followed by sequential interaction mediated by helices α2/α5 of DED-B, to form the procaspase-8 DED chain that is crucial for its activation and subsequent cell death.


Allogeneic pregnancy in B-lymphocyte deprived CBA/Ca mice--effects on maternal lymphoid organs and fetal survival.
A number of female CBA/Ca (H2-k) mice were injected with rabbit-anti mouse IgM every 2 days throughout their life cycle in order to prevent their development of immunocompetent B-lymphocytes. The efficiency of the anti IgM-treatment was good in the group of mice used, and all experimental mice almost completely lacked 1) surface Ig-staining cells (immunoperoxidase ABC method), 2) serum IgG (ELISA technique), and 3) Ig-secreting cells (protein A plaque assay). All experimental mice contained a functioning T-cell pool, as recorded in vitro by conA-stimulation and one-way MLC. At an age of 40-60 days these mice were allowed to mate allogeneically with C57/Bl (H-2b) males. No harmful effects of the anti-IgM treatment on the first pregnancy cycle were found, and B-cell deprived mice delivered as many healthy litters as did the controls. It was also observed that the enlargement of the spleen and uterus-draining nodes was of the same magnitude in both experimental and control mice at the end of the first pregnancy.


Characterizing "fibrofog": Subjective appraisal, objective performance, and task-related brain activity during a working memory task.
The subjective experience of cognitive dysfunction ("fibrofog") is common in fibromyalgia. This study investigated the relation between subjective appraisal of cognitive function, objective cognitive task performance, and brain activity during a cognitive task using functional magnetic resonance imaging (fMRI). Sixteen fibromyalgia patients and 13 healthy pain-free controls completed a battery of questionnaires, including the Multiple Ability Self-Report Questionnaire (MASQ), a measure of self-perceived cognitive difficulties. Participants were evaluated for working memory performance using a modified N-back working memory task while undergoing Blood Oxygen Level Dependent (BOLD) fMRI measurements. Fibromyalgia patients and controls did not differ in working memory performance. Subjective appraisal of cognitive function was associated with better performance (accuracy) on the working memory task in healthy controls but not in fibromyalgia patients. In fibromyalgia patients, increased perceived cognitive difficulty was positively correlated with the severity of their symptoms. BOLD response during the working memory task did not differ between the groups. BOLD response correlated with task accuracy in control subjects but not in fibromyalgia patients. Increased subjective cognitive impairment correlated with decreased BOLD response in both groups but in different anatomic regions. In conclusion, "fibrofog" appears to be better characterized by subjective rather than objective impairment. Neurologic correlates of this subjective experience of impairment might be separate from those involved in the performance of cognitive tasks.


Case report of a Wilms' tumor and a left-sided inferior vena cava. A common tumor with a normal variant of surgical significance.
We report a case of a successful surgical resection of a Wilms' tumor in the right kidney with a coincidental preoperative imaging finding of a left-sided inferior vena cava. To our knowledge, these 2 conditions occurring together has not been previously reported in literature. Diagnostic features and the value of magnetic resonance imaging are emphasized. We also review the literature of major venous anomalies and their influence on surgical procedures carried out on such patients.


Low-generation fluorescent polyurethane dendrimers via late-stage modification using azide-alkyne click chemistry.
Protecting group free one-pot multicomponent Curtius reaction afforded a versatile MN2 type dendron, ensuring late-stage modification of both dendron and dendrimer to afford highly fluorescent symmetrical and unsymmetrical (Janus) polyurethane dendrimers. Fluorescence study of these dendrimers exhibited the Förster resonance energy transfer (FRET) between blue and mint green fluorophores.


Detailed Anatomy of Bridging Veins Around the Foramen Magnum: a Multicenter Study Using Three-dimensional Angiography.
There has been limited literature regarding the bridging veins (BVs) of the medulla oblongata around the foramen magnum (FM). The present study aims to analyze the normal angioarchitecture of the BVs around the FM using slab MIP images of three-dimensional (3D) angiography. We collected 3D angiography data of posterior fossa veins and analyzed the BVs around the FM using slab MIP images. We analyzed the course, outlet, and number of BVs around the FM. We also examined the detection rate and mean diameter of each BV. Of 57 patients, 55 patients (96%) had any BV. The median number of BVs was two (range: 0-5). The BVs originate from the perimedullary veins and run anterolaterally to join the anterior condylar vein (ACV), inferior petrosal sinus, sigmoid sinus, or jugular bulb, inferolaterally to join the suboccipital cavernous sinus (SCS), laterally or posterolaterally to join the marginal sinus (MS), and posteriorly to join the MS or occipital sinus. We classified BVs into five subtypes according to the draining location: ACV, jugular foramen (JF), MS, SCS, and cerebellomedullary cistern (CMC). ACV, JF, MS, SCS, and CMC BVs were detected in 11 (19%), 18 (32%), 32 (56%), 20 (35%), and 16 (28%) patients, respectively. The mean diameter of the BVs other than CMC was 0.6 mm, and that of CMC BV was 0.8 mm. Using venous data from 3D angiography, we detected FM BVs in most cases, and the BVs were connected in various directions.


New estimates of racial/ethnic differences in life expectancy with chronic morbidity and functional loss: evidence from the National Health Interview Survey.
This study documents the mortality, chronic morbidity and physical functioning experiences of U.S. Hispanics, non-Hispanic whites, and non-Hispanic blacks 50 years of age and older in the United States. Hispanics are classified by nativity to better assess an important source of heterogeneity in population health within that population. Drawing on mortality and morbidity data from the National Health Interview Survey, demographic models of healthy life expectancy are used to derive estimates of life expectancy, life expectancy with and without chronic morbidity conditions, and life expectancy with and without functional limitations. The results not only highlight the mortality advantages of foreign-born Hispanics, but also document their health advantages in terms of morbidity and physical functioning beyond age 50. Nativity is a highly important factor differentiating the health and mortality experiences of Hispanics: U.S.-born Hispanics have a health profile more indicative of their minority status while foreign-born Hispanics have much more favorable mortality and health profiles. Differences in smoking across racial/ethnic/nativity groups is suggested as an important reason behind the apparent health advantages of foreign-born Hispanics relative to whites as well as relative to their U.S.-born counterparts.


Labor induction in term gravidas with prelabor rupture of membranes and unfavorable cervixes: Oxytocin versus vaginal misoprostol.
To compare maternal and neonatal outcomes between oxytocin and vaginal misoprostol induction in women with term prelabor rupture of membranes (PROM) and unfavorable cervixes. In this retrospective study, 589 pregnant women with term singleton fetuses in cephalic presentation, reactive nonstress tests, PROM of 2-24 h duration, Bishop score <6, and no previous uterine surgery were reviewed and divided into oxytocin (n = 301) and misoprostol (n = 288) groups. The primary outcomes were the rate of vaginal delivery and delivery within 24 h. After 24 h of induction, the misoprostol group showed a significantly higher proportion of vaginal delivery (64.6% vs. 49.5%, P < 0.001) and a lower cesarean section delivery rate (11.5% vs. 25.2%, P < 0.001) than the oxytocin group. More primiparas in the misoprostol group achieved vaginal delivery within 24 h than in the oxytocin group (60.5% vs. 45.4%, P = 0.001). Among primiparas, the misoprostol group had a significantly lower cesarean delivery rate (12.6% vs. 27.5%, P < 0.001). Vaginal misoprostol induction in term PROM gravidas with unfavorable cervixes was associated with lower cesarean section and higher vaginal delivery rates within 24 h than oxytocin infusion. Vaginal misoprostol and oxytocin infusion had similar maternal and neonatal outcomes.


Frailty and depression: Reciprocal influences or common causes?
Previous research demonstrated substantial associations between frailty and depression in late life, but it remains unclear whether this relationship is best explained by reciprocal influences of these variables or by common causes. This study investigated the interdependencies between frailty and depression across time by examining cross-lagged effects within individuals, while accounting for variability in baseline levels and long-term development between individuals. We modeled longitudinal data from six panel waves gathered in the Survey of Health, Ageing and Retirement in Europe, covering a time period of up to 14 years. The total sample size was N = 58,152 individuals aged 50 years or older. Frailty was based on a deficit accumulation frailty index and depressive symptoms were measured with the EURO-D scale. We used a latent curve model with structured residuals for statistical analysis. The results did not demonstrate relevant cross-lagged effects of frailty and depression at the within-person level. However, within-person increases in frailty were accompanied by within-person increases in depression at the same point in time. At the between-person level, it showed that individuals with higher levels and steeper trajectories in frailty also tend to show higher levels and steeper trajectories in depression. These findings question the notion that frailty and depression reciprocally influence each other over the course of time, but rather indicate that frailty and depression might be both affected by common causes, in both the short and the long term.


Synthesis of methoxylated goniothalamin, aza-goniothalamin and γ-pyrones and their in vitro evaluation against human cancer cells.
The present work describes the preparation of three novel series of compounds based on the structure of goniothalamin, a natural styryl lactone which has been found to display cytotoxic and antiproliferative activities against a variety of cancer cell lines. A focused library of 29 novel goniothalamin analogues was prepared and evaluated against seven human cancer cell lines. While the γ-pyrones and the aza-goniothalamin analogues were less potent than the lead compound, 2,4-dimethoxy analogue 88 has shown to be more potent in vitro than goniothalamin against all cancer cell lines evaluated. Furthermore, it was more potent than doxorubicin against NCI-ADR/RES, OVCAR-03 and HT-29 while being less toxic to human keratinocytes (HaCat). The 3,5-dimethoxy analogue 90 and 2,4,5-trimethoxy analogue 92 also displayed promising antiproliferative activity when compared to goniothalamin (1). These results provide new elements for the design and synthesis of novel representatives of this family of natural compounds.


Treatment of displaced intra-articular calcaneal fractures with triangular tube-to-bar external fixation: long-term clinical follow-up and radiographic analysis.
Sixty-six feet (62 patients) with displaced intra-articular calcaneal fractures underwent manual reduction and distraction with the use of a triangular tube-to-bar external fixation device and were retrospectively reviewed at a minimum of 1-year post-operative. Final radiographic follow-up revealed complete consolidation in all fractures, maintenance of reduction, and limited degenerative osteoarthrosis about the subtalar joint. Our results indicate that with proper application and attention to detail, restoration of calcaneal morphology using triangular tube-to-bar external fixation should be considered a viable alternative in the treatment of displaced intra-articular fractures of the calcaneus.


Cerebrovascular and cardiovascular responses to the Valsalva manoeuvre during hyperthermia.
During hyperthermia, the perturbations in mean arterial blood pressure (MAP) produced by the Valsalva manoeuvre (VM) are more severe. However, whether these more severe VM-induced changes in MAP are translated to the cerebral circulation during hyperthermia is unclear. Healthy participants (n = 12, 1 female, mean ± SD: age 24 ± 3 years) completed a 30 mmHg (mouth pressure) VM for 15 s whilst supine during normothermia and mild hyperthermia. Hyperthermia was induced passively using a liquid conditioning garment with core temperature measured via ingested temperature sensor. Middle cerebral artery blood velocity (MCAv) and MAP were recorded continuously during and post-VM. Tieck's autoregulatory index was calculated from the VM responses, with pulsatility index, an index of pulse velocity (pulse time) and mean MCAv (MCAvmean ) also calculated. Passive heating significantly raised core temperature from baseline (37.9 ± 0.2 vs. 37.1 ± 0.1°C at rest, p < 0.01). MAP during phases I through III of the VM was lower during hyperthermia (interaction effect p < 0.01). Although an interaction effect was observed for MCAvmean (p = 0.02), post-hoc differences indicated only phase IIa was lower during hyperthermia (55 ± 12 vs. 49.3 ± 8 cm s- 1 for normothermia and hyperthermia, respectively, p = 0.03). Pulsatility index was increased 1-min post-VM in both conditions (0.71 ± 0.11 vs. 0.76 ± 0.11 for pre- and post-VM during normothermia, respectively, p = 0.02, and 0.86 ± 0.11 vs. 0.99 ± 0.09 for hyperthermia p < 0.01), although for pulse time only main effects of time (p < 0.01), and condition (p < 0.01) were apparent. These data indicate that the cerebrovascular response to the VM is largely unchanged by mild hyperthermia.


Persistent level 1 hypoglycemia due to hypothyroidism and underlying Neurofibromatosis type 1.
Hypoglycemia in non-diabetic patients is rare and may be due to various etiologies. It is important to recognize hypoglycemia early and appropriately manage hypoglycemia in patients with neurofibromatosis 1 and hypothyroidism. Non-diabetic hypoglycemia is not common and can be seen in certain conditions like Neurofibromatosis type 1 (NF1). We report a rare case of 66-year-old man with hypothyroidism and NF1 who developed a persistent level 1 hypoglycemia.


Cerebral ischemia-reperfusion injury in the gerbil.
Gerbils subjected to cerebral ischemia (unilateral carotid occlusion for 6 hr) were either asymptomatic or developed increasingly severe neurologic deficits which correlated with degrees of brain swelling (weights of ischemic hemisphere versus the contralateral control hemispheres) following 3 hr of reperfusion. Asymptomatic gerbils or gerbils suffering only mild deficits survived for 1 week following reperfusion while gerbils suffering moderate to severe deficits had a poor survival rate with only 22% remaining alive after 1 week.


Prognostic value of chromosome 1 and 8 copy number in invasive ductal breast carcinoma among Iranian women: an interphase FISH analysis.
Breast cancer is amongst the leading causes of death in women worldwide and the most common cancer amongst Iranian women. Unfortunately, the current clinical and histological criteria can only help 60 percent of women with breast cancer in diagnosis and long-term treatment. Therefore, genetic markers both at single gene and chromosomal level can play an important role in improving the diagnosis and prognosis of breast cancer patients. The aim of this retrospective study was to investigate the role of chromosome 1 and 8 copy number assessed by interphase fluorescence in situ hybridization (FISH), as prognostic parameters in 50 Iranian women, aged 35 to 64 years, with sporadic invasive ductal breast carcinoma. Chromosome 1 and 8 copy numbers were evaluated in relation to established clinicopathological parameters, the immunohistochemical markers ER, PR, P53 and cathepsin D, DNA index by flow cytometry, age and survival status of the patients. FISH using centromeric probes for chromosomes 1 and 8 was applied to interphase cell suspensions prepared from archived, Carnoyfixed tumor cells and selected paraffin-embedded tumor sections. Aneusomy for chromosomes 1 and 8 was present in all 50 patients to different levels. The total abnormality rate for chromosome 1 was 33.92 percent (4.24 percent monosomy and 29.68 percent polysomy), whereas for chromosome 8 this rate was 28.30 percent (6.48 percent monosomy and 21.82 percent polysomy). Statistically significant association (p<0.05) was demonstrated between monosomy 1 and patients' age below 50 years, and between monosomy 1 and poor survival, respectively. Disomy 8 was significantly associated with P53 expression. A borderline significant correlation was demonstrated between polysomy 8 and diploid DNA content, as well as between disomy 1 and disease-free status of the patients. Chromosome 1 and 8 copy numbers may be considered as useful prognostic markers in invasive ductal carcinoma of the breast.


Pregnancy among adolescent girls in humanitarian settings: a case in refugee camp of Gambella regional state, community-based cross-sectional study, Southwest Ethiopia, 2021.
The aim of this study was to assess the prevalence of pregnancy and associated factors among adolescent girls in Nguenyyiel Refugee Camp. Cross-sectional study was employed to conduct this study. A community-based cross-sectional study was done in Nguenyyiel Refugee Camp. Four hundred and fourteen adolescent girls participated in this study. The systematic random sampling technique was used to select respondents. Data were collected using a well-structured and pretested questionnaire. Pregnancy test was done using the human chorionic gonadotropin test. Bivariate and multivariate logistic regression analysis was run to identify factors associated with adolescent pregnancy. The prevalence of pregnancy among adolescent girls in the Nguenyyiel Refugee Camp was 21.7% (95% CI: 17.6% to 25.6%). Factors associated with adolescent pregnancy were age (17-19 years) (AOR): 2.79; 95% CI: 1.55 to 5.05; educational status: primary education (AOR: 7.69; 95% CI: 3.55 to 16.68) and no formal education (AOR: 3.42; 95% CI: 1.59 to 7.36); and household living arrangement: living with none of the biological parents (AOR: 2.14; 95% CI: 1.02 to 4.49) and living with either of the biological parent (AOR: 3.71; 95% CI: 1.76 to 7.81). This study showed that there is a high prevalence of pregnancy among adolescent girls in the study setting. Age (17-19 years), educational status and household living arrangement (living with none of the biological parents and living with either of the biological parents) were among the factors significantly associated with adolescent pregnancy. Hence, health workers and other stakeholders in the camps should focus on strengthening adolescent sexual health education giving special attention to late adolescents, uneducated and living without biological family.


Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors.
Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.


Plant hormones: ins and outs of auxin transport.
Regulated transport has long been known to play a key part in action of the plant hormone auxin. Now, at last, a family of auxin efflux carriers has been identified, and the characterisation of one family member has provided strong evidence in support of models that have been proposed to explain gravitropic curvature in roots.


Short scar face-lift with the use of fibrin sealant.
Fibrin sealants have been used in surgical procedures for decades. This article focuses on the short scar face-lift and the applicability of Tisseel fibrin sealant, or "tissue glue," in expediting the healing process in a series of consecutive patients undergoing face-lift surgery. The evolution of the face-lift incision into the short scar and the adjunctive use of the Tisseel fibrin sealant have both resulted in faster recovery.


Inhibition of bovine bone marrow granulocyte/macrophage colony formation in vitro by serum collected from cattle infected with Trypanosoma vivax or Trypanosoma congolense.
Serum collected from cattle infected with Trypanosoma vivax or Trypanosoma congolense inhibited bovine granulocyte/macrophage colony formation in methyl cellulose cultures. Maximum inhibition was caused by serum collected two and three weeks post infection. The degree of inhibition appeared to be related to the degree of parasitemia. Inhibition of erythroid colony formation by serum collected from these animals was not observed.


Using biological metabolites as biomarkers to predict safety and quality of whole and minimally processed spinach.
This study investigated the possible linkage between spinach metabolic biomarkers and their safety and quality during minimally processing and storage. Spinach leaves were treated following the basic minimal processing practices treatments (minimally processed, whole washed, and whole unwashed) and packaged in plastic bags. Significant changes (p < 0.05) in various metabolites biomarkers, physical properties and microbial counts were recorded during the 15 days of refrigerated storage. The contents of vitamin C and polyphenols decreased by 47.82% and 31.62%, respectively, while pH increased from 6.21 ± 0.04 to 6.62 ± 0.04. Furthermore, physical examination revealed significant (p < 0.05) decline in greenness and crispness and increase in yellowness and brownness. Most importantly, CO2 increased gradually and the volatile compounds such as 2-methyl furan, 1-octen-3-ol and 3-octadien-3-one started to emerge after 8 days of storage, while (E)-2-pentenal, (E)-2-hexanal and (Z)-2-hexen-1-ol disappeared. These changes in volatile compounds correlated with the significant (p < 0.05) increase (4.93 log CFUg-1) in the microbial counts and hence can be considered as metabolite markers of quality and safety of spinach.


Prospective relationship between autistic traits and nutrient intakes among Japanese children: Results of the Shika study.
It is known about food selectivity among children with autism spectrum disorder. However, the nutritional inadequacy among children with ASD is not clear. Especially, long-term evaluation has not been studied. We examined the prospective relationship between autistic traits in children and subsequent nutrient intake in later childhood. We utilized data obtained at two time points from a study conducted in Japan. Participants were 759 Japanese children aged between 7 and 12 years at baseline and between 10 and 15 years in the follow-up. The results showed relatively lower intakes of sodium, calcium, magnesium, iron, vitamin D, vitamin B2, and vitamin B12 among children with than without autistic traits. Relatively lower intake of minerals and vitamins in children with autistic traits is more evident in later childhood. The results suggest the importance of screening the nutrient intake of children with autistic traits across childhood.


[Clinical analysis of neurofibromatosis in oral and maxillofacial regions treated with staged operations and laser therapy].
To evaluate the clinical effect of neurofibromatosis in the oral and maxillofacial region treated with staged operations and laser therapy. Eight cases with neurofibromatosis were treated with staged operations, laser therapy was used for hemostasis during operation, cafe-au-lait was treated with Q-switched laser. The average amount of bleeding was 100-400 ml, no hemorrhagic shock occurred intraoperatively. All patients were of good facial appearance, cafe-au-lait was improved during short-term follow-up. Staged operations and laser therapy is a valuable treatment for neurofibromatosis in the oral and maxillofacial region.


Association of psychological resilience and cognitive function in older adults: Based on the Ma' anshan Healthy Aging Cohort Study.
The purpose of this study was to explore whether psychological resilience can influence changes in cognitive function in older adults and provide clues and rationale for improving cognitive function and preventing the onset of dementia in the geriatric population. A total of 2495 older adults aged 60 years or older from the Ma' anshan Healthy Aging Cohort were included in the study. Participants' cognitive functioning and psychological resilience were measured using the MMSE (mini-mental state examination) scale and the SRQS (stress resilience quotient scale) scale during the 5 years of follow-up, and the association was explored. Those with MMSE scores ≤ 17 in the illiterate group, ≤ 20 in the elementary school group, and ≤ 24 in the secondary school and above group were considered cognitive impairment. The prevalence of cognitive impairment increased from 6.89% to 14.30% during the five years of follow-up. At 5-year follow-up, the group with the highest psychological resilience had 41 (6.83%) individuals whose cognitive functioning changed from normal to cognitive impairment, while the group with the worst psychological resilience had 114 (18.33%) individuals. The study also found a significant effect of different levels of psychological resilience on changes in cognitive functioning after adjusting for potential confounders. Compared with Q1 (the reference group), the Odds ratio of cognitive decline in Q2, Q3 and Q4 groups were 0.51(0.42,0.64), 0.37(0.29,0.47) and 0.19(0.13,0.27), respectively. Improving the level of psychological resilience in older adults may be one way to prevent the incidence of cognitive impairment.


A whole image of the hippocampal pyramidal neuron revealed by intracellular pressure-injection of horseradish peroxidase.
The intracellular pressure-injection of HRP was applied to the rat hippocampus and has brought an excellent presentation of the Golgi-like image of the pyramidal neuron. Rats were allowed to survive for 3 days and brain sections were treated with the PAP-immunohistochemical technique to enhance the sensitivity of HRP neurohistochemistry. The pyramidal neuron densely developed axon branches in the ipsilateral hippocampus and sent the commissural axon to the contralateral hippocampus. Moreover, short axon branches diverged from the commissural axon to the bilateral septal nuclei.


Localisation of glutamate receptor binding sites and mRNAs to the dorsal horn of the rat spinal cord.
The autoradiographic distribution of binding sites for [3H]AMPA, [3H]kainate, [3H]MK-801 and [3H]L-glutamate and the in situ hybridization of GluR-A, GluR-B, GluR-C and GluR-D in rat spinal cord sections were determined. All of the radioligands had similar localisations with the dorsal horn being the most intensely labelled region. In the in situ hybridization experiments only the GluR-B mRNA was detected at high levels in the spinal cord with predominant expression in the substantia gelatinosa. These results support electrophysiological evidence for the presence of glutamate activated neurones in the spinal cord and suggest that these excitatory pathways are confined mainly to the dorsal horn.


Experimental investigation on the effects of the standoff distance and the initial radius on the dynamics of a single bubble near a rigid wall in an ultrasonic field.
Bubble behaviors near a boundary in an ultrasonic field are the fundamental forms of acoustic cavitation and of substantial importance in various applications, such as industry cleaning, chemical engineering and food processing. The effects of two important factors that strongly affect the dynamics of a single acoustic cavitation bubble, namely, the initial bubble radius and the standoff distance, were investigated in this work. The temporal evolution of the bubble was recorded using high speed microphotography. Meanwhile, the time of bubble collapse and the characteristics of the liquid jets were analyzed. The results demonstrate that the intensity of the acoustic cavitation, which is characterized by the time of bubble collapse and the liquid jet speed, reaches the optimum level under suitable values of the initial bubble radius and the normalized standoff distance. As the initial bubble radius and the normalized standoff distance increase or decrease from the optimal values, the time of the bubble collapse increases, and the first liquid jet's speed decreases substantially, whereas the speeds of the second and third liquid jets exhibit no substantial changes. These results on bubble dynamics in an ultrasonic field are important for identifying or correcting the mechanisms of acoustic cavitation and for facilitating its optimization and application.


Changes in quality of life after balloon treatment followed by gastric banding in severely obese patients--the use of two different quality of life questionnaires.
Improvements in quality of life (QOL) obtained by weight loss have mainly been reported after bariatric surgery. QOL has not been investigated in surgical patients first losing weight by nonsurgical means followed by a surgical intervention and never simultaneously by two QOL-a generic and a disease-specific-questionnaires. Prospective data were obtained from 40 consecutive patients (mean age 36.6 years, body weight 142.4 kg, body mass index (BMI) 46.5 kg/m2). Two different QOL questionnaires, the generic Medical Outcomes Study Short Form-36 (SF-36) and the disease-specific Health-Related Quality of Life (HRQL) questionnaire, were evaluated at three points in time: at the start, 3 months after the placement of an intragastric balloon that remained in situ for 6 months, and 3 months after subsequent gastric banding. QOL scores revealed a significant improvement in many health domains, with an earlier improvement with the disease-specific HRQL, whereas the generic QOL questionnaire lagged behind. However, in the end, the SF-36 caught up completely to normal-weight levels, whereas some scales of the HRQL remained below these levels. Work productivity and involvement in sports improved significantly. BMI declined significantly over time, but no correlation with SF-36 and HRQL score changes was found. The QOL improved substantially independent of changes in BMI. Because of the divergent outcomes of generic and disease-specific QOL questionnaires, prospective studies should examine the sensitivity to changes of both kinds of QOL questionnaires.


Analysis of lead isotopic ratios of glass objects with the aim of comparing them for forensic purposes.
This paper presents the possibilities of applying the likelihood ratio (LR) approach for the comparison problem to the data collected as a result of the Isotope Ratio Mass Spectrometry (IRMS) analysis targeted at lead (Pb)-isotope ratios. The assessment of the applied LR models performance was conducted by an Empirical Cross Entropy (ECE) approach. 35 glass samples were subjected to IRMS analysis and were described by Pb-isotope ratios: (208)Pb/(204)Pb, (207)Pb/(204)Pb, (206)Pb/(204)Pb, (208)Pb/(206)Pb, and (207)Pb/(206)Pb. Univariate and bivariate LR computations were performed, assuming normally distributed data subjected or not to a logarithmic transformation. Principal Component Analysis (PCA) was employed for creating orthogonal variables to propose an alternative LR model. It was found that the application of variable (208)Pb/(204)Pb seems to be promising as it delivers one of the lowest percentages of false positive and false negative rates as well as being the only variable for which an ECE plot gave satisfactory results.


Autoimmunity to neuronal nicotinic acetylcholine receptors.
Nicotinic acetylcholine receptors (nAChRs) are widely expressed in many and diverse cell types, participating in various functions of cells, tissues and systems. In this review, we focus on the autoimmunity against neuronal nAChRs, the specific autoantibodies and their mechanisms of pathological action in selected autoimmune diseases. We summarize the current relevant knowledge from human diseases as well as from experimental models of autoimmune neurological disorders related to antibodies against neuronal nAChR subunits. Despite the well-studied high immunogenicity of the muscle nAChRs where autoantibodies are the main pathogen of myasthenia gravis, autoimmunity to neuronal nAChRs seems infrequent, except for the autoantibodies to the ganglionic receptor, the α3 subunit containing nAChR (α3-nAChR), which are detected and are likely pathogenic in Autoimmune Autonomic Ganglionopathy (AAG). We describe the detection, presence and function of these antibodies and especially the recent development of a cell-based assay (CBA) which, contrary to until recently available assays, is highly specific for AAG. Rare reports of autoantibodies to the other neuronal nAChR subtypes include a few cases of antibodies to α7 and/or α4β2 nAChRs in Rasmussen encephalitis, schizophrenia, autoimmune meningoencephalomyelitis, and in some myasthenia gravis patients with concurrent CNS symptoms. Neuronal-type nAChRs are also present in several non-excitable tissues, however the presence and possible role of antibodies against them needs further verification. It is likely that the future development of more sensitive and disease-specific assays would reveal that neuronal nAChR autoantibodies are much more frequent and may explain the mechanisms of some seronegative autoimmune diseases.


Heightened response to e-cigarettes in COPD.
E-cigarettes induce greater inflammatory mediators from COPD lung cells; therefore, the risks of e-cigarette use in COPD might be greater than in people without COPD http://ow.ly/xmnN30nzDhX.


Caval anastomosis in liver transplantation: prospective experience of Verona liver transplantation program.
Caval anastomosis in liver transplantation has been modified to avoid outflow complications. Classic cava replacement is rarely indicated; most liver transplantation teams use a piggy-back (PB) technique. At the start of our liver transplantation program, we opted for a latero-lateral (L-L) caval anastomosis. In our prospective experience, the L-L caval anastamosis was safe and feasible in all 24 adult patients. No vascular complications occurred. Graft and patient survival rates were both 96% at 11 months follow-up.


SAM1 domain of SASH1 harbors distinctive structural heterogeneity.
The sterile alpha motif (SAM) domains are among the most versatile protein domains in biology, and the variety of the oligomerization states contribute to their diverse roles in many diseases. A better understanding of the structure and dynamics of various SAM domains will provide a scientific basis for drug development targeting them. Here, we used SEC-MALS, HPLC, NMR, and other biophysical techniques to characterize the structural features and dynamics of the SAM1 domain in SASH1. SASH1 is a scaffold protein belonging to the same family as SASH3. Unlike the dimerization seen in SASH3's SAM domain, our SEC-MALS and SE-HPLC showed that SAM1 exists primarily as a less compact monomer with a minor oligomer. NMR assignment, relaxation, and exchange experiments revealed the presence of both a disordered monomer and a more structured oligomer with multiple timescale exchange regimes in solution. Mutagenesis and SE-HPLC showed that D663A/T664K substitutions in SAM1 increased its oligomerization. In sum, this study is the first to characterize a disordered structure for a SAM domain, provides additional evidence and framework for the diversity of SAM domains, and identifies a region in SAM1 as a potential starting point to further characterize the structural mechanism of oligomerization of the domain.


Injection of nonvariceal bleeding lesions of the upper gastrointestinal tract.
In a prospective series 102 non-variceal upper GI bleeders were studied. An indication for endoscopic injection therapy was seen in 63 patients. In accordance with bleeding intensity, 27 patients were grouped as Forrest Ia, 37 as Forrest Ib, 8 as Forrest II with a "visible vessel" and 13 as Forrest II without one. Definitive hemostasis was achieved in almost 100% of the cases. Within the Forrest Ia group mortality was lowered to 11% as compared with 20% within the emergency surgery group. More than 80% of patients had at least one severe coexistent illness. The aim of endoscopic injection is to avoid surgery in high-risk patients.


General and specific microscopic characteristics of the dorsal tail scales and the spines of the crest in the tuatara Sphenodon pucntatus (Reptilia; Rhynchocephalia; Sphenodontidae).
Dorsal crest scales and those of the tail spines of the tuatara (Sphenodon punctatus) represent different specializations involved in display and protection. Erection of the dorsal crest occurs in males during combat and courtship, but tail spines are not noticeably involved in these activities. In both scale derivatives corneous beta proteins (CBPs, formerly called beta-keratins) and intermediate filaments keratins (IFKs) were determined by immunolabelling. The dermis is dense with few sparse fibrocytes surrounded by collagen bundles, the latter rather randomly oriented in the crest scales. In the tail ridge scales banded collagen I fibrils form more regular, orthogonally aligned bundles of alternating layers with connections to the basal epidermal membrane. A conglomerate of dermal melanonophores and iridophores is present under the epidermis. The iridophores are the likely origin of the whitish colour of the crest. The epidermis shows a thicker beta-layer with serrated/indented corneocytes in the tail scales while the beta layer is reduced in the crest but contains CBPs. A relatively thick mesos layer is present in both scale derivatives, especially in the crest where its role, aside from limiting transpiration, is not known. The alpha-layer is formed by corneocytes with irregular perimeter and sparse desmosomal remnants. The high labelling intensity for CBPs in the beta-layer disappears in the mesos layer but occurs, albeit strongly reduced, in the alpha-layer as in the other body scales. The take-home message is that the dense dermis and its apical beta-layer strengthen mechanically the ridge spines while the crest is mainly supported by the firm but pliable and less dense or regular dermis.


A chimera of a gelatinase inhibitor peptide with streptavidin as a bifunctional tumor targeting reagent.
A chimeric protein, consisting of streptavidin fused to a cyclic decapeptide with potent inhibitory activity for matrix metalloproteinases (MMP), has been produced in Escherichia coli and purified. The purified chimera formed a tetramer and showed full biotin-binding ability. The chimera was also capable of both binding to MMP-2 and inhibiting its activity. Thus, both the streptavidin moiety and the decapeptide of the chimera are fully functional. This bifunctional nature of the chimera should facilitate the application of the decapeptide since the streptavidin moiety can be used as a specific conjugation site for almost any materials upon biotinylation.


Hepatitis B virus and hepatitis B-related viral infection in renal transplant recipients. A prospective study of 90 patients.
Hepatitis B virus (HBV) infection may induce severe hepatitis and affect long-term survival of kidney transplant recipients. Persistent viral infection has been shown to occur despite the absence of usual serologic markers. The liver and serum HBV deoxyribonucleic acid (DNA) status of 90 patients were studied prospectively; recently transplanted patients, both hepatitis B virus surface antigen (HBsAg)-positive and negative, with and without liver disease, were investigated with HBV serology, serum HBV DNA, and liver histology. Thirty-four patients had detectable HBsAg, and 21 had viral multiplication at the time of transplantation. Serial HBV DNA determinations performed in 57 of 90 patients disclosed (a) reactivation of HBV replication in 11 of 12 HBsAg-positive patients, (b) increase of viral replication when positive on the initial sample in 6 of 11 patients, and (c) development of HBV replication in 7 of 35 of the HBsAg-negative patients. Moreover, liver HBV DNA studies showed a statistical correlation between the presence of integrated liver HBV DNA and chronic hepatitis in HBsAg-negative patients. This study demonstrates prospectively the significant association of HBsAg-positive as well as HBsAg-negative HBV infection with chronic hepatitis and suggests that immunosuppressive therapy may enhance the viral replication in both HBsAg-positive and negative subjects.


Three-dimensional vertebral wedging in mild and moderate adolescent idiopathic scoliosis.
Vertebral wedging is associated with spinal deformity progression in adolescent idiopathic scoliosis. Reporting frontal and sagittal wedging separately could be misleading since these are projected values of a single three-dimensional deformation of the vertebral body. The objectives of this study were to determine if three-dimensional vertebral body wedging is present in mild scoliosis and if there are a preferential vertebral level, position and plane of deformation with increasing scoliotic severity. Twenty-seven adolescent idiopathic scoliotic girls with mild to moderate Cobb angles (10° to 50°) participated in this study. All subjects had at least one set of bi-planar radiographs taken with the EOS® X-ray imaging system prior to any treatment. Subjects were divided into two groups, separating the mild (under 20°) from the moderate (20° and over) spinal scoliotic deformities. Wedging was calculated in three different geometric planes with respect to the smallest edge of the vertebral body. Factorial analyses of variance revealed a main effect for the scoliosis severity but no main effect of vertebral Levels (apex and each of the three vertebrae above and below it) (F = 1.78, p = 0.101). Main effects of vertebral Positions (apex and above or below it) (F = 4.20, p = 0.015) and wedging Planes (F = 34.36, p<0.001) were also noted. Post-hoc analysis demonstrated a greater wedging in the inferior group of vertebrae (3.6°) than the superior group (2.9°, p = 0.019) and a significantly greater wedging (p≤0.03) along the sagittal plane (4.3°). Vertebral wedging was present in mild scoliosis and increased as the scoliosis progressed. The greater wedging of the inferior group of vertebrae could be important in estimating the most distal vertebral segment to be restrained by bracing or to be fused in surgery. Largest vertebral body wedging values obtained in the sagittal plane support the claim that scoliosis could be initiated through a hypokyphosis.


Rare presentation of inflammatory myofibroblastic tumor in the kidney.
Inflammatory myofibroblastic tumor (IMT) is a rare pathologic entity that has been mostly described in the lung. It has been reported in nearly every organ, with occurrence in the kidney being extremely rare. IMT has nonspecific clinical and radiological findings and often mimics a malignant process. This is a case discussing the radiologic and pathologic findings of a renal IMT in a 35-year-old female who underwent radical nephrectomy for a right renal pelvis mass that was mistaken for transitional cell carcinoma.


Nonrestricted differential intoxication of cells by pertussis toxin.
After uptake and retrograde transport pertussis toxin acts by ADP-ribosylating alpha-Gi proteins. We show that uptake via many different receptor proteins followed by retrograde transport and intoxication is not restricted to a particular cell type. The efficiency of cellular intoxication, however, was found to be cell type dependent.


Reconstruction of hypopharyngeal defects in cancer surgery: do we have a choice?
Between 1982 and 1985, 83 patients with hypopharyngeal or extensive laryngeal cancers underwent pharyngoesophagectomy (48 patients), circumferential pharyngectomy (8 patients), and partial pharyngectomy (27 patients), depending on the site and extent of tumor involvement. The resultant hypopharyngeal defects were reconstructed with gastric transposition, a tubed pectoralis major myocutaneous flap, and a pectoralis major flap patch, respectively. There were three hospital deaths in the gastric transposition group (6 percent) and none in both pectoralis major flap groups. The leakage rate was 8.3 percent in the gastric transposition group, 25 percent in the tubed pectoralis major flap group, and 3.7 percent in the pectoralis major flap patch group. Stricture was avoided with the interdigitation technique used at the tubed-flap-to-esophagus anastomosis, although the fistula rate was high. The overall complication rate was higher with gastric transposition. Although swallowing was satisfactory in all three groups, 42 percent of the patients with gastric transposition experienced regurgitation. Over a follow-up period of 16 to 50 months the local recurrence rate was 5 percent, and the actuarial survival rate was 55 percent at 24 months.


17β-Estradiol infusions into the dorsal striatum rapidly increase dorsal striatal dopamine release in vivo.
Systemic injections of 17β-estradiol (E2) in ovariectomized (OVX) female rats rapidly enhance dorsal striatal dopamine (DA) release in response to amphetamine (AMPH). Additionally, a single injection of E2 rapidly (within 30min) enhances amphetamine-induced DA release. In situ studies show that this rapid effect of E2 occurs specifically within the dorsal striatum (DS). The present study investigated the in vivo effects of E2 infused into the DS, medial prefrontal cortex (mPFC) or the substantia nigra (SN) on dorsal striatal DA release. Rats were OVX and implanted with a silastic tube containing 5% E2 in cholesterol, previously shown to mimic low physiological serum concentrations of 18-32pg/ml. Single-probe microdialysis was used to measure extracellular DA levels in the DS. In addition, DA release was measured subsequent to systemic injections of the indirect DA agonist, AMPH (0.5mg/kg SC), administered simultaneously with E2 (0.544μg/100μl) or its vehicle, cyclodextrin (VEH) (0.520μg/100μl). Local infusions of E2 into the DS resulted in a greater amphetamine-induced dorsal striatal DA release in comparison to vehicle. Local infusions of E2 into the mPFC or the SN did not result in an enhancement of amphetamine-induced DA levels in the DS. These studies suggest that increases in dorsal striatal DA release in response to systemic E2 are a consequence of E2 actions within the DS itself.


Characterisation of granulocyte stimulation by thionins from European mistletoe and from wheat.
Thionins are small basic peptides found in different plant species, which are known to exert cytotoxic properties. In addition, previous data indicated an activation of human granulocytes by thionins from European mistletoe (viscotoxins, VT). To extend these latter findings, we investigated the influence of VT and from thionins from wheat flour (purothionin) on human granulocytes by flow cytometry and tried to characterise the involved molecular structures and mechanisms. Phagocytosis was determined by incorporation of FITC-labelled Escherichia coli and respiratory burst by oxidation of dihydrorhodamine 123 to rhodamine 123. VT and purothionin significantly enhanced E. coli-stimulated phagocytosis and respiratory burst at 25 and 250 microgram/ml. Phagocytosis of damaged lymphocytes by granulocytes was detected by electron microscopy in the VT-stimulated (100 microgram/ml) but not in the control cultures. The poly-cationic structure of the intact molecule seems to be crucial, as evidenced by comparison of the burst and phagocytosis-enhancing effects induced by other poly-cationic (protamine sulphate, histone, poly-l-arginine, poly-l-lysine) and poly-anionic (poly-l-glutamic acid) peptides, while pore forming due to amphipathic properties seems to be less important. Ca2+ and Mg2+ could not inhibit VT-enhanced phagocytosis and, thus, could not inhibit binding of VT to granulocytes. In addition, verapamil at low concentrations inhibited VT activity, suggesting the involvement of Ca2+ channels for granulocyte activation by the VT. Similarly, thionins and histones in contrast to protamine sulphate induced cell death of granulocytes at 250 microgram/ml as demonstrated by an enhanced release of reactive oxygen intermediates in unstimulated granulocytes. From these data one may suggest that activity of VT is induced by strong unspecific ionic binding, probably followed by specific receptor binding, and thionins exhibit stimulatory and cytotoxic effects on immune cells, which have to be further characterised.


The in vivo labeling with acetate and palmitate of lung phospholipids from developing and adult rabbits.
The labeling with radiolabeled acetate and palmitate of lung, microsomes isolated from lung, and surfactant phospholipids from adult, 3-day-old, and newborn rabbits was studied. The half-life of phosphatidylcholine from lung and microsomal fractions was shorter when labeled with acetate than when labeled with palmitate. Half-time values similarly measured for phosphatidylglycerol, phosphatidylinositol or phosphatidylethanolamine were not different for the two labels. Acetate and palmitate-labeled phospholipids appeared in the surfactant fraction with similar accumulation curves. The relative specific activities of acetate-labeled phosphatidylcholine from adult, 3-day-old, and newborn rabbits, respectively, were 1.30, 1.86 and 1.77 times those measured for those measured for the palmitate label. Surfactant phosphatidylinositol and phosphatidylethanolamine from 3-day-old animals similarly were labeled preferentially with acetate. However, phosphatidylglycerol purified from the surfactant fraction contained equivalent relative amounts of the acetate and palmitate labels in 3-day-old and adult rabbits. These results suggest that the type II pneumocyte may use acetate preferentially for the synthesis of palmitic acid which then is incorporated into surfactant phospholipids.


Frequency distribution and 'reference values' of plasma alkaline phosphatase (EC 184.108.40.206) activity in the adult population of a Scottish new town.
As part of a study to establish the prevalence of renal calculus disease, alkaline phosphatase activity was measured by the method recommended by the Scandinavian Society for Clinical Chemistry and Clinical Physiology in the plasma of 3823 adults from the Scottish new town of Cumbernauld. The enzyme activity differs in males and females and increases with age. Reference ranges are presented.


You Are What You Eat... or Are You?
In this issue of Developmental Cell, Hosios et al. (2016) take a rigorous and quantitative approach to analyze metabolite acquisition and allocation in proliferating cultured mammalian cells. This work clarifies what we know while providing a new analytical framework to undergird future work on the metabolism of proliferating cells.


A comprehensive modeling framework to evaluate soil erosion by water and tillage.
Soil erosion is significantly increased and accelerated by unsustainable agricultural activities, resulting in one of the major threats to soil health and water quality worldwide. Quantifying soil erosion under different conservation practices is important for watershed management and a framework that can capture the spatio-temporal dynamics of soil erosion by water is required. In this paper, a modeling framework that coupled physically based models, Water Erosion Prediction Project (WEPP) and MIKE SHE/MIKE 11, was presented. Daily soil loss at a grid-scale resolution was determined using WEPP and the transport processes were simulated using a generic advection dispersion equation in MIKE SHE/MIKE 11 models. The framework facilitated the physical simulation of sediment production at the field scale and transport processes across the watershed. The coupled model was tested using an intensively managed agricultural watershed in Illinois. The impacts of no-till practice on both sediment production and sediment yield were evaluated using scenario-based simulations with different fractions of no-till and conventional tillage combinations. The results showed that if no-till were implemented for all fields throughout the watershed, 76% and 72% reductions in total soil loss and sediment yield, respectively, can be achieved. In addition, if no-till practice were implemented in the most vulnerable areas to sediment production across the watershed, a 40% no-till implementation can achieve almost the same reduction as 100% no-till implementation. Based on the simulation results, the impacts of no-till practice are more prominent if implemented where it is most needed.


Improvement of kojic acid production in Aspergillus oryzae AR-47 mutant strain by combined mutagenesis.
Kojic acid is a kind of secondary metabolites, whose biosynthesis pathway remains unclear to date. It is produced industrially by microbial fermentation, and thus, mutagenesis breeding still plays a vital role for obtaining strains with high kojic acid production. The starting strain KA-11 isolated from mildewed fruits was identified as Aspergillus oryzae and then subjected to a combined mutagenesis program including microwave mutagenesis, UV irradiation, heat-LiCl, atmospheric, and room temperature plasma (ARTP). The kojic acid production was increased by 47.0%, 87.1%, 126.2%, and 292.3% compared with the starting strain KA-11 after each mutagenesis stage. A mutant strain AR-47 with kojic acid production of 96.5 g/L in flask-shake fermentation was finally obtained. The fermentation time also decreased from 7 to 5 days. Real-time quantitative PCR was used to determine the transcriptional expression levels of genes that may be relevant to kojic acid biosynthesis, including kojA, kojR, kojT, AO090113000141, AO090113000143, AO090113000145, nrtA, and laeA. The results showed that the transcriptional expression levels of all these genes in high yield strain AR-47 had increased compared with the starting strain KA-11.


Muscle satellite (stem) cell activation during local tissue injury and repair.
In post-mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin-like growth factor-I (IGF-l) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF-I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF-IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M-cadherin (M-cad) and related to the expression of the two forms of IGF-I. It was found that the following local damage MGF expression preceded that of M-cad whereas IGF-IEa peaked later than M-cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF-IEa to maintain protein synthesis to complete the repair.


SARS-CoV-2 infection in the context of Kawasaki disease and multisystem inflammatory syndrome in children.
Recent studies have noted an increasing number of Kawasaki-like cases in the pediatric population following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the literature, the condition is described as multiple inflammatory syndrome in children (MIS-C) or pediatric inflammatory syndrome (PIMS). A similar clinical course of Kawasaki disease (KD) and MIS-C causes difficulties in distinguishing between both conditions. However, the differential diagnosis is crucial since patients with MIS-C can present severe symptoms (myocardial dysfunction, fever, mucocutaneous symptoms) and require more extensive monitoring during treatment than children diagnosed with KD. Along with assessing epidemiological and genetic factors, it is imperative to estimate the risk of developing MIS-C in KD patients with confirmed SARS-CoV-2 infection. Genetic predispositions, such as the ITPKC gene polymorphism in KD, ACE deletion (D) polymorphism in SARS-CoV-2, and inborn errors of immunity (IEIs) in MIS-C affect the regulation of immune system complex clearances and cellular adaptations. The virus has a tropism for both vascular and respiratory cells, which further causes additional symptoms necessitating standard therapy with antithrombotic treatment. The diagnostic criteria for KD, MIS-C, and SARS-CoV-2 help differentiate each condition and optimize treatment strategies. Unfortunately, long-term outcomes in KD patients who develop MIS-C due to SARS-CoV-2 infection have been inadequately documented due to the timing of the pandemic, further displaying the need for longitudinal studies in these patients. This review underlines the differences in diagnosis and treatment of KD and MIS-C. Overall, children with KD may develop MIS-C in the setting of SARS-CoV-2 infection, but further research is needed to outline specific etiologies, prognostic factors, and diagnoses.


Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced: the PUMA trial.
Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC. Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival. PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques. ClinicalTrials.gov: NCT05237453 .


Impaired Dynamic Cerebral Autoregulation in Patients With Cerebral Venous Sinus Thrombosis: Evaluation Using Transcranial Doppler and Silent Reading Stimulation.
Cerebral venous sinus thrombosis (CVST) may impair dynamic cerebral autoregulation (dCA) of the middle cerebral artery (MCA). However, most studies have focused on dCA of the MCA; a few studies are based on the posterior cerebral artery (PCA) during silent reading and neurovascular coupling (NVC). This study explored the effects of CVST on dCA of the MCA and PCA during silent reading and NVC. From January 2021 to August 2022, 60 CVST patients and 30 controls were enrolled in this study. Non-invasive continuous beat-to-beat blood pressure, cerebral blood flow velocity and other associated information on the MCA and PCA during silent reading were collected using a transcranial Doppler. NVC assessment was performed by opening and closing the eyes periodically based on voice prompts, and eye-opening visual stimulation was achieved by silently reading Chinese tourism materials. Visual stimulation signals can selectively activate Brodmann's areas 17, 18, and 19 of the occipital when reading silently with open eyes, prompting them to release neurotransmitters and dilate PCA. dCA was determined by transfer function analysis. In dCA of the PCA during silent reading, the CVST group's very low frequency phase was lower than that of the control group (p = 0.047). In NVC, the difference in the indexes of the cerebrovascular conductance and visually evoked flow response of the CVST group were lower than those of the control group (p = 0.017 and p = 0.019, respectively). Compared with the control group, dCA and NVC of the PCA during silent reading were impaired in CVST patients.


Aggregation-induced emission of a novel conjugated phosphonium salt and its application in mitochondrial imaging.
A new conjugated phosphonium salt TPP was synthesized readily from phosphine-triggered ring-opening of 2,4,5-triphenylpyrylium salt. In aqueous solution, it exhibited interesting AIEE properties and self-assembled into fluorescent nanoparticles, which can be used as a fluorescence probe to image mitochondria in cells.


Plasma nitrendipine concentrations in elderly normotensive volunteers after single and multiple dosing.
An acute and chronic dosing pharmacokinetic study of the calcium antagonist nitrendipine was carried out in 8 normotensive volunteers (mean age 80.1 +/- 3.4 years) to investigate if drug accumulation occurred in the elderly. Subjects received 10 mg nitrendipine once daily by mouth for 8 days. Plasma nitrendipine concentrations before administration and at 0.5, 1, 2, 4, 6 and 8 hours after dosing were measured after the first and last dose. Comparison of the pharmacokinetic data from Days 1 and 8 failed to show any evidence of nitrendipine accumulation in these elderly subjects.


Influence of hydrological regime and land cover on traits and potential export capacity of adult aquatic insects from river channels.
Despite many studies highlighting the widespread occurrence and effects of resource movement between ecosystems, comparatively little is known about how anthropogenic alterations to ecosystems affect the strength, direction and importance of such fluxes. Hydrological regime and riparian land use cause well-documented changes in riverine larval invertebrate communities. Using a dataset from 66 sites collected over 20 years, we showed that such effects led to spatial and temporal differences in the density and type of larvae with winged adults within a river reach, altering the size and composition of the source pool from which adult aquatic insects can emerge. Mean annual larval densities varied 33-fold and the temporal range varied more than 20-fold between sites, associated with the hydrological regime and land cover and antecedent high and low flows, respectively. Densities of larvae with winged adults were greater in sites that had more algal coverage, agricultural land use, seasonally predictable flow regimes and faster water velocities. More interestingly, by influencing larval communities, riparian land use and the magnitude and frequency of high and low flows affected the size structure, dispersal ability and longevity of adults available to emerge from river reaches, potentially influencing the spatial extent and type of terrestrial consumers supported by aquatic prey. This suggests that anthropogenic alterations to land use or river flows will have both spatial and temporal effects on the flux and potential availability of adult aquatic insects to terrestrial consumers in many rivers.


Whole-genome sequencing elucidates the species-wide diversity and evolution of fungicide resistance in the early blight pathogen Alternaria solani.
Early blight of potato is caused by the fungal pathogen Alternaria solani and is an increasing problem worldwide. The primary strategy to control the disease is applying fungicides such as succinate dehydrogenase inhibitors (SDHI). SDHI-resistant strains, showing reduced sensitivity to treatments, appeared in Germany in 2013, shortly after the introduction of SDHIs. Two primary mutations in the SDH complex (SdhB-H278Y and SdhC-H134R) have been frequently found throughout Europe. How these resistances arose and spread, and whether they are linked to other genomic features, remains unknown. For this project, we performed whole-genome sequencing for 48 A. solani isolates from potato fields across Europe to better characterize the pathogen's genetic diversity in general and understand the development and spread of the genetic mutations that lead to SDHI resistance. The isolates can be grouped into seven genotypes. These genotypes do not show a geographical pattern but appear spread throughout Europe. We found clear evidence for recombination on the genome, and the observed admixtures might indicate a higher adaptive potential of the fungus than previously thought. Yet, we cannot link the observed recombination events to different Sdh mutations. The same Sdh mutations appear in different, non-admixed genetic backgrounds; therefore, we conclude they arose independently. Our research gives insights into the genetic diversity of A. solani on a genome level. The mixed occurrence of different genotypes, apparent admixture in the populations, and evidence for recombination indicate higher genomic complexity than anticipated. The conclusion that SDHI tolerance arose multiple times independently has important implications for future fungicide resistance management strategies. These should not solely focus on preventing the spread of isolates between locations but also on limiting population size and the selective pressure posed by fungicides in a given field to avoid the rise of new mutations in other genetic backgrounds.


Psychosocial distress during pregnancy and the risk of infantile colic: a follow-up study.
To examine the association between psychosocial exposures during pregnancy and the risk of infantile colic. The study included 378 infants and was conducted as a substudy of the Danish National Birth Cohort from 1997 to 1999, with prenatal data collected twice during pregnancy. A diary with a record for postpartum weeks 4-8 was used to quantify the amount of the infants' crying and fussing. The cumulative incidence proportion of infantile colic was 8.2%. A threefold increased risk of infantile colic (OR = 3.7; 95% CI: 1.1-13.2) was found for mothers who reported distress during pregnancy. Close to a twofold increased risk of IC was found for the women who scored higher than 8 on the psychological distress scale (adjusted OR = 1.9; 95% CI: 0.5-7.2). The results indicate that general distress during pregnancy influences the risk of infantile colic. Whether or not this relationship is causal requires further investigations.


Effects of syntactic features on sentence-picture matching in Broca's aphasics: a reply to Drai and Grodzinksy (2005).
We reanalyzed the data in , considering individual patients' responses to different sentence types to be non-independent events. The analyses revealed effects of two of the three factors identified by Drai and Grodzinsky--constituent movement and passive mood. The result is inconsistent with the trace deletion hypothesis; we conclude that features of syntactic structure other than constituent movement are relevant to understanding performance variation in patients with Broca's aphasia.


Single-Molecule Force Spectroscopy of Membrane Protein Folding.
Single-molecule force spectroscopy is a unique method that can probe the structural changes of single proteins at a high spatiotemporal resolution while mechanically manipulating them over a wide force range. Here, we review the current understanding of membrane protein folding learned by using the force spectroscopy approach. Membrane protein folding in lipid bilayers is one of the most complex biological processes in which diverse lipid molecules and chaperone proteins are intricately involved. The approach of single protein forced unfolding in lipid bilayers has produced important findings and insights into membrane protein folding. This review provides an overview of the forced unfolding approach, including recent achievements and technical advances. Progress in the methods can reveal more interesting cases of membrane protein folding and clarify general mechanisms and principles.


Genome-Wide Identification, Classification and Expression Analysis of m6A Gene Family in Solanum lycopersicum.
Advanced knowledge of messenger RNA (mRNA) N6-methyladenosine (m6A) and DNA N6-methyldeoxyadenosine (6 mA) redefine our understanding of these epigenetic modifications. Both m6A and 6mA carry important information for gene regulation, and the corresponding catalytic enzymes sometimes belong to the same gene family and need to be distinguished. However, a comprehensive analysis of the m6A gene family in tomato remains obscure. Here, 24 putative m6A genes and their family genes in tomato were identified and renamed according to BLASTP and phylogenetic analysis. Chromosomal location, synteny, phylogenetic, and structural analyses were performed, unravelling distinct evolutionary relationships between the MT-A70, ALKBH, and YTH protein families, respectively. Most of the 24 genes had extensive tissue expression, and 9 genes could be clustered in a similar expression trend. Besides, SlYTH1 and SlYTH3A showed a different expression pattern in leaf and fruit development. Additionally, qPCR data revealed the expression variation under multiple abiotic stresses, and LC-MS/MS determination exhibited that the cold stress decreased the level of N6 2'-O dimethyladenosine (m6Am). Notably, the orthologs of newly identified single-strand DNA (ssDNA) 6mA writer-eraser-reader also existed in the tomato genome. Our study provides comprehensive information on m6A components and their family proteins in tomato and will facilitate further functional analysis of the tomato N6-methyladenosine modification genes.


Risk factors for massive hemorrhage during the treatment of cesarean scar pregnancy: a systematic review and meta-analysis.
Cesarean scar pregnancy (CSP) is one of the serious complications associated with cesarean delivery (CD). This meta-analysis aims to identify risk factors associated with massive hemorrhage during the CSP treatment. Eight electronic databases were searched for case-control studies published before December 31th, 2018, which compared the possible factors causing massive bleeding during the CSP treatment. Quantitative synthesis was performed by RevMan 5.3. Sensitivity analysis and publication bias were performed by Stata 12.0. Total 20 case - control studies including 3101 CSP patients with previous CD met the inclusion criteria. Bleeding group had 573 patients and the control group had 2528 patients. The risk factors for massive bleeding during CSP treatment included multiple gravidities (MD = 0.15, 95% CI 0.03-0.28, P = 0.73), big maximum diameter of gestation sac (MD = 18.49 mm, 95%CI 15.34-21.65, P < 0.01), high gestational days (MD = 8.98 days, 95% CI 4.12-13.84, P < 0.01), high β-HCG level (MD = 21.39 IU/ml, 95% CI 7.36-35.41, P = 0.03; MD = 3.02 U/ml, 95% CI 0.21-5.84, P < 0.01) and rich blood flow around the lesion (OR = 6.73, 95% CI 3.93-11.51, P = 0.59). While, thick myometrium (MD = - 4.94 mm, 95% CI - 6.12 to - 3.75, P < 0.01) may be protective factor. Multiple gravidities, big gestation sac, large gestational days, high serum β-HCG level, abundant blood supply to pregnancy sac and thin myometrium maybe the risk factors for massive bleeding during the CSP treatment.


New players in the 5-HT receptor field: genes and knockouts.
In recent years, cloning has revealed the existence of no less than 14 mammalian 5-HT receptors, as well as evidence that isoforms of the 5-HT4 and 5-HT7 receptors are generated by alternative splicing. In addition, molecular biology techniques have provided new tools with which to study the function of 5-HT receptors. For example, new technologies are emerging that will allow the generation of either inducible or tissue-specific knockouts (or both). In this review José Lucas and René Hen focus on the characteristics of the most recently cloned receptors and the contribution of molecular biology to the understanding of 5-HT receptor function.


Auditory N1 and P2 attenuation in action observation: An event-related potential study considering effects of temporal predictability and individualism.
Tones that are generated by self-performed actions elicit attenuated N1 and P2 amplitudes, as measured by electroencephalography (EEG), compared to identical external tones, which is referred to as neurophysiological sensory attenuation (SA). At the same time, self-generated tones are perceived as less loud compared to external tones (perceptual SA). Action observation led in part to a similar neurophysiological and perceptual SA. The perceptual SA in observers was found in comparison to tones that were temporally predictable, and one study suggested that perceptual SA in observers might depend on the cultural dimension of individualism. In this study, we examined neurophysiological SA for tones elicited by self-performed and observed actions during simultaneous EEG acquisitions in two participants, extending the paradigm with a visual cue condition controlling for effects of temporal predictability. Moreover, we investigated the effect of individualism on neurophysiological SA in action observation. Relative to un-cued external tones, the N1 was only descriptively reduced for tones that were elicited by self-performed or observed actions and significantly attenuated for cued external tones. A P2 attenuation effect relative to un-cued external tones was found in all three conditions, with stronger effects for self- and other-generated tones than for cued external tones. We found no evidence for an effect of individualism. These findings add to previous evidence for neurophysiological SA in action performance and observation with a paradigm well-controlled for the effect of predictability and individualism, showing differential effects of the former on the N1 and P2 components, and no effect of the latter.


Persistence of immobilised and total urease and phosphatase activities in a soil amended with organic wastes.
This paper reports on the persistence of total and immobilised enzyme activities (urease and phosphatase) in a soil amended with organic wastes containing high levels of total-urease and phosphatase activity. Fresh organic materials showed the highest values for both total-enzymatic activities. The addition of organic waste to soil increased both total-enzymatic activities in the soil, which, after 360 days, showed values above those of the control. Immobilised enzymes were also higher in the fresh wastes than in the soil with compost, while the specific enzymatic activity levels (enzymatic activity per unit of carbon) were similar. The immobilised urease activity was greater in the amended soil than in the control. At the beginning of the incubation period, the immobilised urease activity was significantly higher in the soil amended with fresh organic wastes than with compost. However, this activity decreased with incubation, whilst the compost-immobilised urease activity increased with time. The effect of organic amendment on immobilised phosphatase activity was similar to that shown by immobilised urease but less pronounced. The persistence of both enzymes was significantly higher in the soil amended with compost than in that amended with fresh materials.


Insights into the transcriptional regulation of the anthracycline reductase AKR7A2 in human cardiomyocytes.
Aldo-Keto Reductase Family 7 Member A2 (AKR7A2) is the most abundant anthracycline metabolizing enzyme in human myocardium. Myocardial AKR7A2 contributes to the synthesis of cardiotoxic C-13 anthracycline alcohol metabolites (e.g., doxorubicinol). The factors that govern the transcription of human AKR7A2 in cardiomyocytes remain largely unexplored. In this study, we performed the functional characterization of the AKR7A2 gene promoter in human AC16 cardiomyocytes. Experiments with gene reporter constructs and chromatin immunoprecipitation assays suggest that NF-κB binds to specific regions in the AKR7A2 promoter. Doxorubicin treatment modified the cellular levels of NF-κB and the expression of AKR7A2. Moreover, doxorubicin treatment led to changes in the pattern of AKR7A2 phosphorylation status. Our results suggest that AKR7A2 expression in human cardiomyocytes is mediated by NF-κB through conserved response elements in the proximal gene promoter region. This study provides the first insights into the functional characteristics of the human AKR7A2 gene promoter.


Immunizing health care workers against influenza: a glimpse into the challenges with voluntary programs and considerations for mandatory policies.
Vaccination of health care workers (HCWs) is an important patient safety initiative. It prevents influenza infection among patients and reduces staff illness and absenteeism. Despite these benefits, HCW influenza immunization uptake is low. Therefore, strategies to achieve high immunization coverage in HCWs, barriers to uptake, and perceptions of mandatory influenza immunization policies were discussed in key informant interviews with influenza immunization program planners. We conducted telephone interviews with 23 influenza immunization program planners from 21 organizations (7 acute care hospitals, 6 continuing care facilities, and 8 public health organizations) across Canada. We used content analysis to identify themes from the interviews. Participants used a variety of promotional and educational activities, and many vaccine delivery approaches, to support HCW immunization programs. Barriers to achieving high coverage in HCWs included misconceptions about the safety and effectiveness of the influenza vaccine, negative personal experiences associated with the vaccine, and antivaccine sentiments. Participants mentioned mandatory influenza immunizations as a solution to low coverage. However, they identified challenges with this approach such as obtaining support from stakeholders, enforcement, and limiting personal autonomy. Participants believed immunization coverage in health care organizations will continue to be suboptimal using existing program strategies. Although participants discussed mandatory immunization as a way to improve uptake, potential obstacles will need to be addressed for this to be implemented successfully.