Ultrastructure of mesoderm in embryos of Opisthopatus roseus (Onychophora, Peripatopsidae): revision of the "long germ band" hypothesis for Opisthopatus.
In previous studies, an unusual pattern of development which resembles the "long germ band" development of some insects has been described in the onychophoran Opisthopatus cinctipes. This pattern has been proposed to be a characteristic of the genus Opisthopatus. To test this assumption, the ultrastructure of embryos of O. roseus, the sister species of O. cinctipes, was examined. Two kinds of paired, segmentally arranged coelomic cavities were found in the embryos studied: 1) dorsolateral coelomic cavities lined by extremely thin epithelia, and 2) ventral coelomic cavities situated within the anlagen of ventrolateral body appendages. Only the dorsolateral coelomic cavities can be considered "somites," since they occur earlier during embryogenesis. This is in contrast with the previous view that suggested a ventral position of "somites" in O. cinctipes. In addition, an anterior-to-posterior gradient occurs in the development of O. roseus. Based on our findings, we reevaluated the previous data on O. cinctipes. From this survey, no evidence in support of a "long germ band" hypothesis in Opisthopatus was found. Instead, the embryogenesis in representatives of Opisthopatus is more similar to that in other onychophorans than expected.


New automated nonisotopic immunoassays for free thyroxin: effect of albumin and thyroxin-binding globulin concentrations.
Recently, nonisotopic (often automated) immunoassays for measuring serum free thyroxin (FT4) have become available. Though more costly than radioimmunoassays, they are considerably more convenient. We studied the influence of endogenous albumin and thyroxin-binding globulin concentration on five automated, nonisotopic methods of measuring FT4 [Enzymun on ES300 (one-step), Stratus I and II (essentially two-step), Delfia (two-step), and IMx (two-step)] in a mixed patient population. We observed that they (a) are influenced very little by endogenous serum binding proteins and (b) seem to have sufficient within-run precision to justify performing single measurements on patients' specimens.


Influence of axial limb rotation on radiographic lower limb alignment: a systematic review.
The influence of limb malrotation on long-leg radiographs (LLR) is frequently discussed in literature. This systematic review aimed to describe the influence of limb rotation on alignment measurements alone and in combination with knee flexion, and determine its clinical impact. A literature search was conducted in June 2021 using the databases MEDLINE, Cochrane, Web of Science (Clarivate Analytics), and Embase. The search term ((radiograph OR X-ray) AND (position OR rotation) AND limb alignment) was used. Database query, record screening, and study inclusion and exclusion were performed by two reviewers independently. Experimental studies (using either specimens or synthetic bones) or clinical studies (prospective or retrospective using radiographs of patients) analyzing the influence of limb rotation on anatomic and mechanical limb alignment measurements were included. Characteristics and results of the included studies were summarized, simplified, and grouped for comparison to answer the research question. Studies were compared descriptively, and no meta-analysis was performed. A total of 22 studies were included showing large heterogeneity, comprising studies with cadavers, patients, and synthetic bones. Most studies (7 out of 8) reported that external rotation (ER) causes less apparent valgus and leads to more varus and internal rotation (IR) causes more valgus and leads to less varus. However, there is no consensus on the extent of rotation influencing alignment measures. Studies reported about an average change of > 2° (n = 4) and < 2° (n = 4) hip-knee-ankle angle (HKA) between 15°IR and 15°ER. There is a consensus that the impact of rotation on mechanical alignment is higher if additional sagittal knee angulation, such as knee flexion, is present. All five studies analyzing the influence of rotation combined with knee flexion (5°-15°) showed an HKA change of > 2° between 15°IR and 15°ER. Malrotation is frequently present on LLR, possibly influencing the measured alignment especially in knees with extension deficit. Surgeons must consider this when measuring and treating deformities (high tibial osteotomy or total knee arthroplasties), and analyzing surgical outcomes. Especially in patients with osteoarthritis with knee extension deficits or postoperative swelling, the effect of malrotation is significantly greater.


[Negative valence systems in the system of research domain criteria : Empirical results and new developments].
The research domain criteria (RDoC) domain of negative valence systems can be used to subsume long established and recently developed research approaches, which build upon theoretical knowledge and clinical practice of various psychiatric disorders. This article outlines how the five constructs within the RDoC domain of negative valence systems can contribute to integrating empirical studies into a coherent and differentiated biopsychosocial model. This is a qualitative review article that summarizes empirical results and discusses new developments on the basis of exemplary studies and selected reviews. The RDoC domain of negative valence systems differentiates in three constructs the time horizon, in which persons need to adequately react to (1) acute, (2) potential, and (3) sustained threats elicited by negative stimuli or situations. These three constructs can be outlined relatively well with specific experimental paradigms and neuronal circuits. Two further constructs focus on the negative consequences of (4) losses and (5) frustrative non-rewards. The former seems to be currently relatively diffusely defined whereas the latter is clearly circumscribed by its relation to specific forms of aggression. Behavioral, physiological, and neuronal reactions to acute and potential threats can be well compared between humans and animals and can be specified with the help of mathematical models. These models can contribute to a better understanding of how healthy and diseased persons process negative stimuli or situations.


Domestication of Chili Pepper Has Altered Fruit Traits Affecting the Oviposition and Feeding Behavior of the Pepper Weevil.
The pepper weevil, Anthonomus eugenii, Cano (Coleoptera: Curculionidae), is one of the most destructive pests of chili pepper. It causes extensive damage on varieties selected for consumption. However, the occurrence of this pest on wild and ornamental peppers remains unknown. We investigated the consequences of chili domestication on the feeding and oviposition of A. eugenii on fruits and flowers. We used plants of one wild accession, Bird Eye Pepper, five ornamental varieties (Pops Yellow, Black Pearl, Sedona Sun, Chilli Chilli, and Salsa Deep), and two domesticated varieties selected for consumption (Scotch Bonnet and Jalapeño). First, we characterized the plants according to their fruit and flower sizes, pericarp thickness, capsaicin level, fruit position, and flower color. Then, we evaluated the susceptibility of fruits and flowers to A. eugenii. Overall, domestication increased fruit and flower sizes and pericarp thickness, altered capsaicin levels, and altered fruit position and flower color. Weevils laid more eggs and caused more feeding damage on varieties selected for consumption than on wild and ornamental plants. Our results add to the growing literature on the consequences of crop domestication on herbivores. This knowledge could be integrated into breeding programs to select varieties resistant against the pepper weevil.


Induction of antigen-specific human T suppressor cells by membrane and soluble ILT3.
Antigen-specific CD8 suppressor T cells (CD8(+) Ts) are adaptive regulatory T cells that are induced in vivo and in vitro by chronic antigenic stimulation of human T cells. CD8(+) Ts induce the upregulation of the inhibitory receptors ILT3 and ILT4 on monocytes and dendritic cells rendering these antigen presenting cells (APCs) tolerogenic. Tolerogenic APCs induce CD4(+) T helper anergy and elicit the differentiation of CD4(+) and CD8(+) T regulatory/suppressor cells. Overexpression of membrane ILT3 in APC results in inhibition of NF-κB activation, transcription of inflammatory cytokines and costimulatory molecules. Soluble ILT3-Fc which contains only the extracellular, Ig-like domain linked to mutated IgG1 Fc, is strongly immunosuppressive. ILT3-Fc, induces the differentiation of human CD8(+) Ts which inhibit CD4(+) Th and CD8(+) CTL effector function both in vitro and in vivo. The acquisition of Ts' function by primed CD8(+) T cells treated with ILT3-Fc was demonstrated to be the effect of the significant upregulation of BCL6, a transcriptional repressor of IL-2, IFN-gamma, IL-5 and granzyme B. The upregulated expression of BCL6, SOCS1 and DUSP10 is integral to the signature of ILT3-Fc-induced CD8(+) Ts. These genes are known inhibitors of cytokine production and TCR signaling and are targeted by miRNAs which are suppressed by ILT3-Fc. ILT3-Fc induces tolerance to allogeneic human islets and reverses rejection after its onset in a humanized NOD/SCID mouse model. Based on these findings we postulate that ILT3-Fc may become an important new agent for treatment of autoimmunity and transplant rejection.


Loss of Growth arrest specific gene 6 (Gas6) results in altered GnRH neuron migration, delayed vaginal opening and sexual maturation in mice.
Prior work has shown the importance of TAM (Tyro3, Axl, Mer) receptor tyrosine kinases in GnRH neuronal development and reproductive function. It is unclear if TAM receptor actions are dependent on ligand activation for their functional effects; thus, we characterized reproductive phenotype of ligand Growth arrest specific gene (Gas6) null mice. Gas6 null mice showed delayed vaginal opening and delayed first estrus. Animals eventually attained normal estrous cycles as adults. The GnRH neuronal population was significantly decreased in Gas6 null adults and embryos, but the final positioning of cell bodies in the hypothalamus was normal. Vaginal tissue showed up-regulation of TAM receptor mRNAs in the absence of the ligand. These data confirm that Gas6 plays a role in early GnRH neuronal development and during vaginal opening. The phenotype of Gas6 KO mice suggests that TAMs function in a ligand-dependent and independent manner to control GnRH neuron development to modulate normal reproductive function.


Correlation of prolactin levels and PRL-receptor expression with Stat and Mapk cell signaling in the prostate of long-term sexually active rats.
Prolactin (PRL) is a key hormone for prostate function, with a basal level in serum and associated with two characteristic circadian peaks. In the male rat, the execution of one bout of sexual behavior with consecutive ejaculations produces a significant transient increase in PRL. However, the impact of a constant sexual life on both PRL levels and prostate function is unknown. Thus, by using constantly copulating males we analyzed the levels of serum PRL, the effect on prostate PRL receptors, and activation of pStat3, pStat5 and Mapk signaling pathways. Sexually experienced Wistar male rats were used, which underwent periodic sessions of sexual behavior tests. Males were subjected to a session of sexual behavior to achieve at least one and up to four ejaculations. Of these, a blood sample was collected from randomly selected males and the ventral prostate was removed for analysis. Serum PRL was quantified, the mRNA for PRL receptors was determined, and signaling pathways were analyzed. Data show that a constant sexual life produced a constant elevation of PRL in serum during four consecutive ejaculations. The ventral prostate showed a different mRNA expression profile for the long and short isoform of the PRL receptor, and both mRNA levels increased. Although the gland did not show modification of the activation of the pStat5 signaling pathway, the levels of pStat3 increased, and the Mapk pathway showed one significant elevation after the third ejaculation. Thus, we showed that an active and constant sexual life produces a sustained increase in serum PRL, its receptors, and the pStat3 signaling pathway. These responses seem to underlie the required physiological need to produce the quantity and quality of prostatic semen to ensure the appropriate environment for sperm to reach and fertilize the ovum.


TIGIT and PD-1 expression atlas predicts response to adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer.
TIGIT and PD-1 are checkpoint receptors that could regulate the functional status of immune cells through independent pathways. However, the clinical significance of immune classification based on TIGIT and PD-1 expression remains unclear in muscle-invasive bladder cancer (MIBC). Patients with MIBC from four independent cohorts were categorised into three clusters. Survival analysis conducted through Kaplan-Meier curves and Cox regression model. Immune contexture was measured by immunohistochemistry and CIBERSORT algorithm. Twenty-five fresh tumour tissue samples were utilised to evaluate functional state of CD8+ T cells by flow cytometry. Cluster I (TIGITlowPD-1low) contained widely poor immune infiltrates with higher FGFR3 mutation, Cluster II (TIGITlowPD-1high) exhibited a highly infiltrated contexture with increased cytolytic CD8+ T cells and had the best prognosis, Cluster III (TIGIThigh) presented a suppressive tumour microenvironment (TME) featured by exhausted CD8+ T cells and basal molecular subtype. Patients of Cluster III had the worst survival but could benefit more from adjuvant chemotherapy and anti-PD-L1 immunotherapy, and also presented limited FGFR3 signalling signature but activated immunotherapeutic and EGFR-associated pathway. TIGIT/PD-1-based risk stratification with distinct immune and molecular features could be served as a predictor for systematic therapeutic response including adjuvant chemotherapy and immunotherapy in MIBC patients.


A phase II trial of lanreotide for the prevention of postoperative pancreatic fistula.
Clinically relevant postoperative pancreatic fistula (CR-POPF) is a significant contributor to morbidity after pancreatectomy. Somatostatin analogues have shown variable efficacy in the prevention of CR-POPF. Lanreotide is a somatostatin analogue ideally suited for perioperative use due to its long half-life and favorable side effect profile. We conducted a phase II single-arm trial of a single dose of preoperative lanreotide (120 mg) in patients undergoing either pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). The primary outcome was development of CR-POPF or intra-abdominal abscess. Secondary outcomes included biochemical leak and overall morbidity. A total of 98 patients completed the study. Sixty-two underwent PD (63.3%) and 36 underwent DP (36.7%). The primary outcome was observed in eight (8%) patients in the overall cohort, one from the DP group and seven from the PD group. Biochemical leak was detected in 12 (12.2%) patients in the overall cohort. Twenty-seven (27.5%) patients developed complications, of which 14 (14.2%) were major complications. Drug-related adverse events were limited to mild skin reactions in two (2%) patients. Patients who received preoperative lanreotide developed CR-POPF at rates significantly lower than historical controls or published literature. This provides strong justification for a randomized controlled trial.


Elevated islet amyloid pancreatic polypeptide and proinsulin in lean gestational diabetes.
Recent research indicates that islet amyloid pancreatic polypeptide (IAPP) might have a regulatory effect on beta-cell insulin processing and secretion. To study such interaction in more detail, IAPP secretion and kinetics and the serum concentrations of proinsulin were assessed both before and after delivery in lean pregnant women with gestational diabetes mellitus (GDM patients) in comparison to those with normal glucose tolerance (NGT) and to nonpregnant healthy lean (control) and obese insulin-resistant women during oral glucose tolerance tests. Kinetic analysis of IAPP was performed with mathematical modeling, providing indirect estimates of its secretion and fractional clearance. Total insulin secretion per 180 min was elevated by 30% in GDM patients (35 +/- 3 pmol/l) versus control subjects (27 +/- 1 pmol/l) (P < 0.05), but increased even more (190-250%) in obese insulin-resistant women, compared with all other groups (68 +/- 7 pmol/l, P < 0.0005). Pregnancy induced a more marked fourfold increase in apparent total IAPP secretion rate (TIR) (GDM patients, 172 +/- 31 pmol x 1(-1) x 3 h(-1); NGT subjects, 166 +/- 31 pmol x 1(-1) x 3 h(-1); control subjects, 40 +/- 1 pmol 1(-1) x 3 h(-1)) and a twofold rise in its fractional clearance versus control subjects (P < 0.01), whereas in GDM patients a 30% increase of IAPP secretion and a decreased clearance was found, compared with obese insulin-resistant women (TIR, 112 +/- 14 pmol x 1(-1) x 3 h(-1)). The increase in IAPP secretion in both pregnant groups was much higher than that of the insulin groups, resulting in a marked change of the IAPP-insulin cosecretion factor when compared with lean or obese nonpregnant women (P < 0.0005). Associated serum proinsulin and the postprandial (total divided by 180 min) proinsulin-to-insulin ratio were greater in GDM patients versus NGT and control subjects (0.11 +/- 0.01 vs. 0.07 +/- 0.01 and 0.08 +/- 0.01 pmol/l, P < 0.05), while the fasting proinsulin-to-insulin ratio was only increased in GDM patients versus control subjects (0.22 +/- 0.03 vs. 0.13 +/- 0.01 pmol/l, P < 0.05). After delivery, total IAPP secretion (52.4 +/- 1.5 pmol/l) was completely normalized in the GDM group, as were the clearance rate and the IAPP-insulin cosecretion factor. Similarly, serum proinsulin concentrations returned to normal, whereas proinsulin-to-insulin ratios remained elevated. In conclusion, IAPP hypersecretion is characteristic for pregnancy and might partially decrease hyperinsulinemia in pregnancy by inhibiting insulin secretion. Increased proinsulin concentrations and a raised proinsulin-to-insulin ratio, which did not abate following delivery, are specific to GDM and might thus serve as its marker and potentially even identify subjects at high risk for the development of NIDDM.


Identification of the role of RIG-I, MDA-5 and TLR3 in sensing RNA viruses in porcine epithelial cells using lentivirus-driven RNA interference.
Pathogen recognition receptors are essential for antiviral host immune responses. These specialized receptors detect conserved viral compounds and induce type I interferons (IFN) and pro-inflammatory cytokines. Here we evaluated the contribution of RIG-I, MDA-5 and TLR3 to the recognition of classical swine fever (CSFV), foot-and-mouth disease virus (FMDV), vesicular stomatitis virus (VSV) and influenza A virus (IAV) to IFN-β responses in the porcine epithelial cell line PK-15. To this end, we identified porcine gene specific small interfering RNA sequences and employed a lentivirus (LV)-based system to deliver the corresponding short hairpin RNA. With this, gene knockdown cell lines were created and tested with regard to the knockdown levels over time and following IFN-β stimulation. During several passages of the transduced cells, the expression of both the reporter gene eGFP and the reduced RNA levels of the targeted gene were stable, although the latter was relatively variable. IFN-β induced IFN-responsive genes such as RIG-I, but the levels of the silenced cell line remained reduced compared to the control cells. Based on virus-induced IFN-β mRNA responses, our results indicate that in PK-15 cells FMDV-detection is solely mediated by MDA-5, whereas VSV and IAV are mainly detected by RIG-I with a minor contribution of MDA-5, and CSFV is sensed by MDA-5, RIG-I and TLR3.


Validation of the mobile serious game application Touch Surgery™ for cognitive training and assessment of laparoscopic cholecystectomy.
Touch Surgery™ (TS) is a serious gaming application for cognitive task simulation and rehearsal of key steps in surgical procedures. The aim was to establish face, content, and construct validity of TS for laparoscopic cholecystectomy (LC). Furthermore, learning curves with TS and a virtual reality (VR) trainer were compared in a randomized trial. The performance of medical students and general surgeons was compared for all three modules of LC in TS to establish construct validity. Questionnaires assessed face and content validity. For analysis of learning curves, students were randomized to train on VR or TS first, and then switched to the other training modality. Performance data were recorded. 54 Surgeons and 51 medical students completed the validation study. Surgeons outperformed students with TS: patient preparation (students = 45.0 ± 19.1%; surgeons = 57.3 ± 15.2%; p < 0.001), access and laparoscopy (students = 70.2 ± 10.9%; surgeons = 75.9 ± 9.7%; p = 0.008) and LC (students = 69.8 ± 12.4%; surgeons = 77.7 ± 9.6%; p < 0.001). Both groups agreed that TS was a highly useful and realistic application. 46 students were randomized for learning curve analysis. It took them 2-4 attempts to reach a 100% score with TS. Training with TS first did not improve students' performance on the VR trainer; however, students who trained with VR first scored significantly higher in module 3 of TS. TS is an accepted serious gaming application for learning cognitive aspects of LC with established construct, face, and content validity. There appeared to be a synergy between TS and the VR trainer. Therefore, the two training modalities should accompany one another in a multimodal training approach to laparoscopy.


Neoadjuvant stereotactic ablative radiotherapy (SABR) for soft tissue sarcomas of the extremities.
Soft tissue sarcomas (STS) comprise a diverse group of mesenchymal malignancies that require multidisciplinary care. Although surgery remains the primary form of treatment for those with localized disease, radiation therapy (RT) is often incorporated either in the neo- or adjuvant setting. Given the development of modern RT techniques and alternative dosing schedules, stereotactic ablative radiotherapy (SABR) has emerged as a promising technique. However, the current role of SABR in the treatment of STS of the extremities remains uncertain. This was a single-center, prospective, single-arm phase II trial. Patients with localized STS who were candidates for limb-preservation surgery were included. Experimental treatment consisted of SABR with 40 Gy in 5 fractions, administered on alternate days, followed by surgery after a minimum interval of 4 weeks. The primary outcome was the rate of wound complication. Secondary outcomes included 2-year local control (LC), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS) rates (and other toxicities). Twenty-five patients were enrolled between October 2015 and November 2019 and completed the treatment protocol. The median rate of histopathologic regression was 65% (range 0-100) and 20.8% of tumors presented pathologic complete response (pCR). Wound complications were observed in 7/25 patients (28%). Three patients underwent disarticulation by vascular occlusion after plastic reconstruction and one patient was amputated by grade 3 limb dysfunction. After a median follow up of 20.7 months, the 2-year estimated risk of local recurrence, distant metastasis and cause-specific death were 0%, 44.7% and 10.6% respectively. Neoadjuvant SABR appears to improve the pCR for patients with eSTS, with acceptable rate of wound complications. Nevertheless, this benefit should be weighed against the risk of late of vascular toxicity with SABR regimen since, even in a short median follow-up, a higher rate of amputation than expected was observed. A larger sample size with longer follow-up is necessary to conclude the overall safety of this strategy.


Mitochondrial dysfunction in epilepsy.
Mitochondrial dysfunction has been identified as one potential cause of epileptic seizures. Impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon's horn sclerosis and of adult and immature animal models of epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca(2+) homeostasis and generation of reactive oxygen species, their dysfunction strongly affects neuronal excitability and synaptic transmission. Therefore, mitochondrial dysfunction is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant epilepsy. For this reason mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy.


Lingering Identity as Chronically Ill and the Unanticipated Effects of Life-Changing Precision Medicine in Cystic Fibrosis: A Case Report.
Cystic fibrosis (CF) is the leading genetic disease among Caucasians; however, advances in diagnosis and treatment have improved both quality and quantity of life for those affected. A remarkable recent discovery is the triple-drug combination, elexacaftor/tezacaftor/ivacaftor, which has been touted as a "miracle drug" for CF because of its demonstrated efficacy and safety. This case study reports on an adult woman with CF who experienced positive life-changing results from elexacaftor/tezacaftor/ivacaftor, and yet discovered that she lived in fear that its effectiveness would diminish, and her debilitating symptoms would return. Her lingering identity as chronically ill tainted her view of her new life with skepticism and pervasive anxiety. This case highlights a critical need to engage in early, regular and sensitive discussions with patients before initiating treatments that may affect their emotional and mental health and provide referrals or services to meet those emergent needs.


Tumor necrosis factor provokes superoxide anion generation from neutrophils.
We report that tumor necrosis factor (TNF) provokes superoxide anion generation from human neutrophils. Superoxide anion generation was provoked at TNF concentration of 1 X 10(-11) M and maximal generation was attained at TNF concentration of 1 X 10(-9) M. We also show that movements of intracellular calcium may mediate the TNF-stimulated superoxide anion generation because 8-(diethylamino) octyl 3,4,5-trimethoxybenzoate hydrochloride--but not extracellular EGTA--inhibited the generation of superoxide anion. These results suggest that TNF may mediate some mechanisms of host defense by provoking superoxide anion generation from neutrophils.


Homogeneous Reforming of Aqueous Ethylene Glycol to Glycolic Acid and Pure Hydrogen Catalyzed by Pincer-Ruthenium Complexes Capable of Metal-Ligand Cooperation.
Glycolic acid is a useful and important α-hydroxy acid that has broad applications. Herein, the homogeneous ruthenium catalyzed reforming of aqueous ethylene glycol to generate glycolic acid as well as pure hydrogen gas, without concomitant CO2 emission, is reported. This approach provides a clean and sustainable direction to glycolic acid and hydrogen, based on inexpensive, readily available, and renewable ethylene glycol using 0.5 mol % of catalyst. In-depth mechanistic experimental and computational studies highlight key aspects of the PNNH-ligand framework involved in this transformation.


Marguerite Bottard (1822-1906), nurse under Jean-Martin Charcot, portrayed by G. Gilles de la Tourette.
Hospitals in Paris underwent considerable change at the end of the 19th century. As they moved from providing accommodation to care, their mission shifted from helping to healing. The glorification of scientific progress, as opposed to religious obscurantism, affected all of French 'Republican' society, in particular a significant part of the medical profession, led by figures such as D.M. Bourneville, former interne (house officer) under J.M. Charcot and also his publisher. Bourneville helped bring about the creation of nursing schools and the gradual replacement of religious orders by educated secular nurses. Marguerite Bottard, Charcot's chief nurse made famous by A. Brouillet's painting 'Une leçon clinique à La Salpêtrière', would be glorified and decorated as a model for this movement. A letter by G. Gilles de la Tourette to Charcot's successor F. Raymond, never before published, illustrates this progressive current of thought and revisits the struggle to secularise hospitals under the Third Republic in France. At the same time, it renews interest in the exemplary career of a nurse whose name was recently given to a building at La Salpêtrière Hospital.


Diurnal patterns and sex differences in cortisol, 11-ketotestosterone, testosterone, and 17beta-estradiol in the bluebanded goby (Lythrypnus dalli).
The primary goals of this study were to evaluate diurnal patterns of and sex differences in the levels of cortisol, 11-ketotestosterone, testosterone, and 17beta-estradiol in the sex-changing bluebanded goby Lythrypnus dalli. Steroid hormones were collected from water samples and analyzed by enzyme immunoassay. During the breeding season, hormones were sampled from both males and females at seven time points between 0600 and 2000 h. When comparing each time point separately, there were significant overall time effects for cortisol and 17beta-estradiol. Cortisol concentrations were lowest at the 0800-1000 h sampling point and showed a qualitative peak in late morning (1000-1200 h). Concentrations of 17beta-estradiol were elevated at the last sampling point (1800-2000 h). Broader temporal trends were revealed for testosterone and 11-ketotestosterone concentrations, both of which were elevated in the morning. There were no sex differences in overall hormone concentrations or temporal profiles for cortisol, 11-ketotestosterone, or testosterone. Males and females showed similar diurnal patterns of 17beta-estradiol but females had significantly higher water-borne 17beta-estradiol levels than males. The results show the presence of diurnal changes in steroid hormone levels in male and female bluebanded gobies. The lack of sex differences in androgens suggests that males of this species, and perhaps other bi-directional sex-changing species in which males do not exhibit prominent secondary sexual characteristics, do not require persistent elevations in 11-ketotestosterone or testosterone to maintain the male phenotype. Although the role of 17beta-estradiol in maintaining sex differences in sexually plastic species is unclear, our results suggest that, of the hormones measured, 17beta-estradiol has the greatest potential for future studies interested in this question.


Effect of different structural flaxseed lignans on the stability of flaxseed oil-in-water emulsion: An interfacial perspective.
The influences of the different structural flaxseed lignans on flaxseed oil (FO) emulsions during storage and digestion were investigated, focusing on their interfacial behavior. From perspective of interface, more than 60% of secoisolariciresinol (SECO) and the acidic hydrolysates of flaxseed lignan macromolecule (FLEH) were located on the interface of FO emulsions. It improved the stability of FO emulsions both during storage and digestion by inhibiting of free radical penetration and improving their targeted antioxidative activity. By comparison, the secoisolariciresinol diglucoside (SDG) and the alkaline hydrolysates of flaxseed lignan macromolecule (FLE) largely located in the aqueous and exerted lower antioxidative efficiency in emulsions. Moreover, SDG, SECO, FLE and FLEH slowed down the digestive rate of FO in emulsions, which might be due to flaxseed lignans inhibited the activity of digestive enzymes. These findings suggested that the different structural flaxseed lignans had the potential as antioxidants in emulsions during storage and digestion.


An analytic framework using deep learning for prediction of traffic accident injury severity based on contributing factors.
Vulnerable road users (VRUs) are exposed to the highest risk in the road traffic environment. Analyzing contributing factors that affect injury severity facilitates injury severity prediction and further application in developing countermeasures to guarantee VRUs safety. Recently, machine learning approaches have been introduced, in which analyses tend to be one-sided and may ignore important information. To solve this problem, this paper proposes a comprehensive analytic framework that employs a deep learning model referred to as the stacked sparse autoencoder (SSAE) to predict the injury severity of traffic accidents based on contributing factors. The essential idea of the method is to integrate various analyses into an analytical framework that performs corresponding data processing and analysis by different machine learning approaches. In the proposed method, first, we utilize a machine learning approach (i.e., Catboost) to analyze the importance and dependence of the contributing factors to injury severity and remove low correlation factors; second, according to the geographical information, we classify the data into different classes by utilizing a machine learning approach (i.e., k-means clustering); third, by employing high correlation factors, we employ an SSAE-based deep learning model to perform injury severity prediction in each data class. By experiments with a real-world traffic accident dataset, we demonstrated the effectiveness and applicability of the framework. Specifically, (1) the importance and dependence of contributing factors were obtained by CatBoost and the Shapley value, and (2) the SSAE-based deep learning model achieved the best performance compared to other baseline models. The proposed analytic framework can also be utilized for other accident data for severity or other risk indicator analyses involving VRUs safety.


Cost-effectiveness in nuclear medicine.
There are many pressures on nuclear medicine physicians to keep costs down and to produce the most efficacious results for the money spent. A procedure is cost-effective if its benefits (correct diagnosis, effective treatment, etc.) are worth the additional costs (money, radiation dose, etc.). The benefits of diagnostic procedures are measured by test performance (diagnostic efficacy [efficacy-D]), which in turn depends on a specific task: detection, classification, localization, or quantitation. For the detection task, measures of test performance include sensitivity, specificity, predictive value, accuracy, diagnostic utility, posttest versus pretest disease probability, area under a receiver operating characteristic (ROC) curve, and others. Standard measures of test performance in the classification, localization, and quantitation tasks have not yet been developed. Efficacy-M (management efficacy) is a measure of the extent to which a procedure influences patient management appropriately. Efficacy-O (outcome efficacy) is a measure of the success of therapeutic procedures. Some publications illustrating these points are presented. Costs associated with nuclear medicine procedures include money, time, discomfort, possible drug reactions, radiation dose, and the hypothetical risk of radiation-associated cancer. The public's perception of these latter risks, or costs, is much higher than our knowledge would justify. Decision trees are useful for laying out all possible strategies, outcomes, costs, and benefits, and estimating the cost-effectiveness of each strategy. Some articles estimating cost-effectiveness in nuclear medicine are reviewed, although few articles in the literature make any detailed use of decision analysis. Much work remains to be done in forming a coherent, consistent procedure for assessing cost-effectiveness in nuclear medicine.


Transition in the ages at key reproductive events and its determinants in India: evidence from NFHS 1992-93 to 2019-21.
Reproductive health events have changed fertility and family planning needs, depicting the changing life patterns of women and the population to which they belong. Understanding the pattern at which these events occur helps in understanding the fertility pattern, family formation and the idea about health essential needs for women. This paper attempts to see the variation in reproductive events (first cohabitation, first sex and first birth) over three decades and also to see potential contributing factors among the reproductive age group of women using secondary data from Data Source: All rounds of the National Family Health Survey (1992-93 to 2019-2021) have been utilized. Cox Proportional Hazard Model illustrates that all regions have initiated their first birth later than women who belong to the east region similar pattern has been obtained for first cohabitation and first sex except for the central region. Multiple Classification Analysis (MCA) depicts the increasing pattern in the predicted mean age at first cohabitation, sex and birth for all demographic characteristics; the highest increment was found in SC women, Uneducated women and Muslim women. Kaplan Meier Curve demonstrates that women with no education, primary or secondary education are shifting towards higher educated women. Most importantly, the results of the multivariate decomposition analysis (MDA) revealed that education played the largest contribution among the compositional factors in the overall increase in mean ages at key reproductive events. Though reproductive health has long been essential in women's lives, they are still very confined to specific domains. Over time the government has formulated several proper legislative measures relating to various domains of reproductive events. However, given that the large size and heterogeneity in social and cultural norms result in changing ideas and choices regarding the initiation of reproductive events, national policy formulation needs to be improved or amended.


Yes-associated protein regulates the hepatoprotective effect of vitamin D receptor activation through promoting adaptive bile duct remodeling in cholestatic mice.
Mounting clinical evidence has revealed that the vitamin D receptor (VDR) is associated with cholestatic liver injury, although the functions of VDR in this condition remain largely unexplored. Here, we investigated the effects of VDR activation on bile duct ligation (BDL) mice, and the underlying mechanisms were further investigated. A low-calcemic VDR agonist, paricalcitol (PAL, 200 ng/kg), was intraperitoneally injected into BDL mice every other day for 5 days or 28 days. Liver histology, liver function indicators, cholangiocyte proliferation, fibrosis scores, and inflammation were evaluated. Mice treated with PAL were rescued from the decreased survival rate induced by BDL and liver damage was reduced. Mechanistically, PAL promoted cholangiocyte proliferation, which was likely conducive to proliferating bile duct maturation and increased branching of bile ducts. PAL treatment also increased the expression of Yes-associated protein (YAP) and its target protein epithelial cell adhesion molecule (EpCam) and decreased the level of inactive cytoplasmic phosphorylated YAP. YAP knockdown abrogated PAL-induced primary bile duct epithelial cell proliferation, confirmed with YAP inhibitor administration. In addition, BDL-induced liver fibrosis and inflammatory cell infiltration were reduced by PAL treatment at both day 5 and day 28 post-BDL. In conclusion, VDR activation mitigates cholestatic liver injury by promoting adaptive bile duct remodeling through cholangiocytic YAP upregulation. Because PAL is an approved clinical drug, it may be useful for treatment of cholestatic liver disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Involvement of multiple scavenger receptors in advanced glycation end product-induced vessel tube formation in endothelial cells.
Toxic advanced glycation end products (toxic AGEs) derived from glycolaldehyde (AGE3) have been implicated in the development of diabetic vascular complications such as retinopathy characterised by excessive angiogenesis. Different receptor types, such as receptor for AGEs (RAGE), Toll like receptor-4 and scavenger receptors, are expressed in endothelial cells and contribute to AGE-elicited alteration of cell function. In the present study, we examined the involvement of AGE-related receptors on AGE-induced angiogenesis in endothelial cells. The effects of pharmacological inhibitors or receptor neutralizing antibodies on AGE3-induced tube formation were investigated using the in vitro Matrigel tube formation assay in b.End5 cells (mouse endothelial cells). AGE3-induced signalling pathways and receptor expression changes were analysed by Western blot analysis and flow cytometry, respectively. Both FPS-ZM1, a RAGE inhibitor, and fucoidan, a ligand for scavenger receptors, suppressed AGE3-induced tube formation. Cocktails of neutralizing antibodies against the scavenger receptors CD36, CD163 and LOX-1 prevented AGE3-induced tube formation. AGE3 activated mTOR signalling, resulting in facilitation of tube formation. Activation of the AGE-RAGE pathway also led to the upregulation of scavenger receptors. Taken together, our findings suggest that the scavenger receptors CD36, CD163 and LOX-1 in conjunction with the RAGE receptor work together to mediate toxic AGE-induced facilitation of angiogenesis.


Exclusion of interspecific competition reduces scatter-hoarding of Siberian chipmunk Tamias sibiricus: A field study.
Although food availability and the abundance of seed predators have been postulated to affect seed dispersal, it is not clear how seed-eating animals modify their scatter-hoarding strategies in response to different levels of interspecific competition. We placed paired germinated and ungerminated acorns of Quercus mongolica on 30-cm high platforms to exclude potential interspecific competition of the predominant larder hoarders Apodemus peninsulae and Myodes rufocanus, to investigate seed dispersal by a predominant scatter-hoarder, Tamias sibiricus, in the field in north-eastern China. Our results showed that T. sibiricus ate more acorns in situ in the absence of interspecific competition. In the presence of interspecific competition of A. peninsulae and C. rufocanus, however, more acorns were scatter-hoarded by T. sibiricus. Regardless of interspecific competition, germination of acorns showed no significant effects on seed dispersal patterns, inconsistent with the "seed perishability hypothesis" that animals avoid hoarding seeds with high perishability. Exclusion of interspecific competition, though relatively increasing the per capita seed abundance, appears to reduce seed dispersal, scatter-hoarding and seedling establishment. Therefore, we propose that moderate interspecific competition rather than competition exclusion may benefit seed scatter-hoarding and seedling establishment.


Double Immunohistochemical Staining on Formalin-Fixed Paraffin-Embedded Tissue Samples to Study Vascular Co-option.
Vascular co-option is a non-angiogenic mechanism whereby tumor growth and progression move on by hijacking the pre-existing and nonmalignant blood vessels and is employed by various tumors to grow and metastasize.The histopathological identification of co-opted blood vessels is complex, and no specific markers were defined, but it is critical to develop new and possibly more effective therapeutic strategies. Here, in glioblastoma, we show that the co-opted blood vessels can be identified, by double immunohistochemical staining, as weak CD31+ vessels with reduced P-gp expression and proliferation and surrounded by highly proliferating and P-gp- or S100A10-expressing tumor cells. Results can be quantified by the Aperio Colocalization algorithm, which is a valid and robust method to handle and investigate large data sets.


MicroRNA-1182 and let-7a exert synergistic inhibition on invasion, migration and autophagy of cholangiocarcinoma cells through down-regulation of NUAK1.
Cholangiocarcinoma (CCA) is the second most common primary liver malignancy worldwide. Several microRNAs (miRNAs) have been implicated as potential tumor suppressors in CCA. This study aims to explore the potential effects of miR-1182 and let-7a on CCA development. Bioinformatics analysis was conducted to screen differentially expressed genes in CCA, Western blot analysis detected NUAK1 protein expression and RT-qPCR detected miR-1182, let-7a and NUAK1 expression in CCA tissues and cell lines. Dual luciferase reporter gene assay and RIP were applied to validate the relationship between miR-1182 and NUAK1 as well as between let-7a and NUAK1. Functional experiment was conducted to investigate the role of miR-1182, let-7a and NUAK1 in cell migration, proliferation and autophagy. Then, the CCA cells that received various treatments were implanted to mice to establish animal model, followed by tumor observation and HE staining to evaluate lung metastasis. CCA tissues and cells were observed to have a high expression of NUAK1 and poor expression of miR-1182 and let-7a. NUAK1 was indicated as a target gene of miR-1182 and let-7a. Importantly, upregulation of either miR-1182 or let-7a induced autophagy, and inhibited cell progression and in vivo tumor growth and lung metastasis; moreover, combined treatment of miR-1182 and let-7a overexpression presented with enhanced inhibitory effect on NUAK1 expression and CCA progression, but such synergistic effect could be reversed by overexpression of NUAK1. Taken together, the findings suggest the presence of a synergistic antitumor effect of miR-1182 and let-7a on the development of CCA via the down-regulation of NUAK1, providing novel insight into the targeted therapy against CCA.


Overproduction and characterization of the first enzyme of a new aldoxime dehydratase family in Bradyrhizobium sp.
Almost 100 genes within the genus Bradyrhizobium are known to potentially encode aldoxime dehydratases (Oxds), but none of the corresponding proteins have been characterized yet. Aldoximes are natural substances involved in plant defense and auxin synthesis, and Oxds are components of enzymatic cascades enabling bacteria to transform, utilize and detoxify them. The aim of this work was to characterize a representative of the highly conserved Oxds in Bradyrhizobium spp. which include both plant symbionts and members of the soil communities. The selected oxd gene from Bradyrhizobium sp. LTSPM299 was expressed in Escherichia coli, and the corresponding gene product (OxdBr1; GenBank: WP_044589203) was obtained as an N-His6-tagged protein (monomer, 40.7 kDa) with 30-47% identity to Oxds characterized previously. OxdBr1 was most stable at pH ca. 7.0-8.0 and at up to 30 °C. As substrates, the enzyme acted on (aryl)aliphatic aldoximes such as E/Z-phenylacetaldoxime, E/Z-2-phenylpropionaldoxime, E/Z-3-phenylpropionaldoxime, E/Z-indole-3-acetaldoxime, E/Z-propionaldoxime, E/Z-butyraldoxime, E/Z-valeraldoxime and E/Z-isovaleraldoxime. Some of the reaction products of OxdBr1 are substrates of nitrilases occurring in the same genus. Regions upstream of the oxd gene contained genes encoding a putative aliphatic nitrilase and its transcriptional activator, indicating the participation of OxdBr1 in the metabolic route from aldoximes to carboxylic acids.


[Investigation and management of genito-urinary tuberculosis].
Genito-urinary tuberculosis is the fourth most common manifestation of the disease, but it is often underestimated by clinicians because of few and non-specific symptoms and insidious disease course. The most common urinary findings are multiple ureteral stenosis. The most common genital involvement is an epididymal nodule for men and a chronic salpingitis for women. The definite diagnosis of genito-urinary tuberculosis is obtained on the basis of culture studies. Due to the paucibacillary nature of the disease, especially of genital location in woman, a probable or presumptive diagnosis is frequently considered with several parameters including radiological imaging (abdominal CT-scan, pelvic ultrasound, pelvic MRI). Endoscopic and surgical procedures are frequently required to obtain specimens for histopathologic and bacteriological studies. Medical treatment is the method of choice, with a combination of four drugs, namely isoniazid, rifampicin, ethambutol and pyrazinamide, followed by a two-drug regimen, for a total of six month duration. Surgery might be indicated in complicated genito-urinary tuberculosis (decreased renal function, infertility, urologic complaints).


Lipidomics profiling of goose granulosa cell model of stearoyl-CoA desaturase function identifies a pattern of lipid droplets associated with follicle development.
Despite their important functions and nearly ubiquitous presence in cells, an understanding of the biology of intracellular lipid droplets (LDs) in goose follicle development remains limited. An integrated study of lipidomic and transcriptomic analyses was performed in a cellular model of stearoyl-CoA desaturase (SCD) function, to determine the effects of intracellular LDs on follicle development in geese. Numerous internalized LDs, which were generally spherical in shape, were dispersed throughout the cytoplasm of granulosa cells (GCs), as determined using confocal microscopy analysis, with altered SCD expression affecting LD content. GC lipidomic profiling showed that the majority of the differentially abundant lipid classes were glycerophospholipids, including PA, PC, PE, PG, PI, and PS, and glycerolipids, including DG and TG, which enriched glycerophospholipid, sphingolipid, and glycerolipid metabolisms. Furthermore, transcriptomics identified differentially expressed genes (DEGs), some of which were assigned to lipid-related Gene Ontology slim terms. More DEGs were assigned in the SCD-knockdown group than in the SCD-overexpression group. Integration of the significant differentially expressed genes and lipids based on pathway enrichment analysis identified potentially targetable pathways related to glycerolipid/glycerophospholipid metabolism. This study demonstrated the importance of lipids in understanding follicle development, thus providing a potential foundation to decipher the underlying mechanisms of lipid-mediated follicle development.


Study of ethion and lipopolysaccharide interaction on lung in a mouse model.
Ethion is an organophosphate used commonly in India despite being banned in many other countries. The present study was designed to study the interaction of ethion and lipopolysaccharide (LPS) together on lung after single low dose ethion exposure. Mice (n = 20) were alienated into control and treatment groups (n = 10 each). The treatment group was orally fed ethion (8 mg/kg/animal/day) dissolved in corn oil. The animals (n = 5 each) from both the groups were challenged with 80 μg Escherichia coli lipopolysaccharide (LPS) intranasally and the remaining animals (n = 5 each) were administered normal saline solution after 24 h. Ethion along with LPS induced lung inflammation as indicated by increased neutrophils and total leukocyte count (TLC) in broncheoalveolar lavage fluid. Ethion induced histomorphological alterations in lung as shown by increased pulmonary inflammation score in histopathology. Real time PCR analysis showed that ethion followed by LPS resulted significant (p < 0.05) increase in pulmonary Toll-like receptor (TLR)-4 (48.53 fold), interleukin (IL)-1β (7.05 fold) and tumor necrosis factor (TNF)-α (5.74 fold) mRNA expression. LPS co-exposure suggested synergistic effect on TLR4 and TNF-α mRNA expression. Ethion alone or in combination with LPS resulted genotoxicity in blood cells as detected by comet assay. The data suggested single dietary ethion exposure alone or in conjunction with LPS causes lung inflammation and genotoxicity in blood cells.


[The painters and sculptors of the king and "artistic expertise" under Louis XIV].
At the crossroads of institutions, markets ands discourses, artistic expertise under the reign of Louis XIV has not been thoroughly studied. So-called "experts" belonged to the judiciary field: they were called upon to describe, attribute and evaluate paintings and sculptures in probate inventories or in the context of judiciary actions. Their appointment was a real performative act, since experts were chosen by the judge or the parties, without definite criteria. Therefore, experts were often - but not always - artists, either guild masters or academicians.


Dynamic process and mechanism of crude oil release from silty intertidal sediment under different influencing factors.
Under tidal scouring, residual petroleum in the intertidal sediment after oil spills could release again, causing secondary pollution in the marine ecosystem. The current study aimed to investigate the dynamic process and principles of crude oil release from silty intertidal sediment under different influencing factors and screened for the key factors. In this paper, the fitting equations and correlation between the release amount and various factors were explored through the single-factor and orthogonal experiments. Then, the key influencing factors were selected for multi-factor fitting of the release amount. The results showed that the oil release amount rose with the increase in oil concentration, oscillation frequency, and release time, but decreased with an increase in salinity. As the pH decreased, the oil release amount increased. The relationship between release amount and concentration/oscillation frequency can be equipped by the polynomial equation, and the average R2 was 0.95 and 0.84, respectively. The release amount can be fitted by the Lagergren pseudo-second-order kinetic equation with time, with the average R2 0.89. The pH was negatively correlated with the release amount in the fresh contaminated sediment but positively correlated with the weathered one. The correlation between each factor and oil release amount was ranked (from large to small) as oil concentration, oscillation frequency, salinity, time, and pH. At last, a polynomial equation can be fitted between the key influencing factors (oil concentration and oscillation frequency) and the release amount. The results can provide a theoretical basis for predicting the secondary pollution owing to the oil re-release from intertidal sediment.


A case of reinfection with a different variant of SARS-CoV-2: case report.
Coronavirus disease 2019 (COVID-19) was previously thought to have a low reinfection rate, but there are concerns that the reinfection rate will increase with the emergence and spread of mutant variants. This report describes the case of a 36-year-old, non-immunosuppressed man who was infected twice by two different variants of COVID-19 within a relatively short period. A 36-year-old Japanese man with no comorbidities was infected with the E484K variant (R.1 lineage) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms were mild and improved with symptomatic treatment alone. About four months later he presented to another outpatient department with high fever and headache. We diagnosed him as infected with the Alpha variant (B.1.1.7) of SARS-CoV-2 based on SARS-CoV-2 real-time reverse transcription polymerase chain reaction testing (RT-PCR). The patient was hospitalized with high fever. The patient received treatment in the form of anti-inflammatory therapy with corticosteroid and antibacterial chemotherapy. The patient improved without developing severe disease. Concerns have been raised that the reinfection rate of COVID-19 will increase with the emergence of mutant variants. Particularly in mild cases, adequate amounts of neutralizing antibodies may not be produced, and reinfection may thus occur. Continued attention to sufficient infection control is thus essential.


A randomized trial of Lactobacillus rhamnosus IDCC 3201 tyndallizate (RHT3201) for treating atopic dermatitis.
Probiotic therapies, mainly live bacteria, have been proven to be effective in treating atopic dermatitis (AD) with some controversies. Killed probiotics or postbiotics would have immunomodulatory effect in allergic diseases including AD. This study was performed to evaluate the therapeutic effect and safety of tyndallized Lactobacillus rhamnosus (IDCC 3201, isolated from the feces of a Korean breastfed infant, repeated heat-treated and incubated, RHT3201) in children with AD. In a randomized, double-blind, placebo-controlled study, RHT3201 at a dose of 1.0 × 1010 CPU/d or placebo was given in children (aged 1-12 years) with moderate AD for 12 weeks. SCORing of AD (SCORAD) scores, allergic inflammatory markers, and safety parameters were evaluated. For evaluating the therapeutic effects of RHT3201, 33 subjects in each group were analyzed. The change of SCORAD total score at 12 weeks (primary outcome) from baseline was significantly greater in the RHT3201 group (-13.89 ± 10.05) compared to the control group (-8.37 ± 9.95). Levels of eosinophil cationic protein (ECP) and interleukin (IL)-31 showed tendency to decrease in the RHT3201 group and significant decreases in subgroup analysis in AD for ≥50 months. For safety analysis, a total of 100 subjects (50 in the treated group and 50 in the control group) were evaluated, and there were no significant differences in safety parameters between two groups. In children with moderate AD, oral administration of RHT3201 showed the therapeutic effect on AD, the effects in part correlated with decrement of ECP and IL-31, and the effect was more remarkable in subgroup analysis.


Pneumothorax.
Pneumothoraces are classified as spontaneous, traumatic, and iatrogenic. Spontaneous pneumothoraces (SP) occur without recognized lung disease (primary, PSP) or due to an underlying lung disease (secondary, SSP). Treatment of PSP and SSP has been quite heterogeneous in the United States; adoption of the recently published American College of Chest Physicians guidelines will hopefully improve care. Central to these guidelines is the emphasis of observational management of a small pneumothorax in clinically stable PSP patients, and chest tube placement as key initial management in PSP or SSP patients who are unstable or have a large pneumothorax. Traumatic pneumothoraces due to penetrating or nonpenetrating (blunt) trauma usually require the placement of a larger-bore chest tube. Iatrogenic pneumothoraces appear most commonly due to transthoracic needle aspiration and may be treated in carefully selected patients with observation. The presence of underlying emphysema in the setting of an iatrogenic pneumothorax usually mandates placement of a drainage catheter. Newer mechanical ventilation modes and strategies may limit the development of positive pressure ventilation- related iatrogenic pneumothoraces.


CD19-targeted, Raman tagged gold nanourchins as theranostic agents against acute lymphoblastic leukemia.
The incidence of Acute Lymphoblastic Leukemia (ALL) is increasing globally, and it is being clinically addressed by chemotherapy, followed by immunotherapy and stem cell transplantation, all with potential life-threatening toxicities. In the need for more effective therapeutics, newly developed disease-targeted nanocompounds can thus hold real potential. In this paper, we propose a novel nanoparticle-based immunotherapeutic agent against ALL, consisting of antiCD19 antibody-conjugated, polyethylene glycol (PEG)-biocompatibilized, and Nile Blue (NB) Raman reporter-tagged gold nanoparticles of urchin-like shape (GNUs), that have a plasmonic response in the Near Infrared (NIR) spectral range. Transmission electron microscopy (TEM) images of particle-incubated CD19-positive (CD19(+)) CCRF-SB cells show that the antiCD19-PEG-NB-GNU nanocomplex is able to recognize the CD19 B-cell-specific antigen, which is a prerequisite for targeted therapy. The therapeutic effect of the particles is confirmed by cell counting, combined with cell cycle analysis by flow cytometry and MTS assay, which additionally offer insights into their mechanisms of action. Specifically, antiCD19-PEG-NB-GNUs proved superior cytotoxic effect against CCRF-SB cells when compared with the free antibody, by reducing the overall viability below 18% after 7 days treatment at a particle-bound antibody concentration of 0.17 ng/μl. Moreover, by combining their remarkable plasmonic properties with the possibility of Raman tagging, the proposed nanoparticles can also serve as spectroscopic imaging agents inside living cells, which validates their theranostic potential in the field of hematological oncology.


Genome Characterization of Pseudomonas aeruginosa KT1115, a High Di-rhamnolipid-Producing Strain with Strong Oils Metabolizing Ability.
In this study, a wild-type Pseudomonas aeruginosa strain KT1115 with the capability of converting rapeseed oils into di-rhamnolipids, a class of biosurfactants with extensive application potential, was successfully isolated and characterized. Di-rhamnolipids production by microorganism culture provided a mild, eco-friendly, and secure approach for surfactants production instead of conventional chemical synthesis. However, few studies have been attempted to explore the metabolic mechanism behind the high di-rhamnolipids production by P. aeruginosa. Here, we presented the graft genome of a wild-type P. aeruginosa strain KT1115, with emphasis on the analysis of oils metabolism and rhamnolipid synthesis. The availability of the genome sequence provides additional insight into the genetic mechanism enhancing di-rhamnolipids biosynthesis.


Recent advances in the CRANK software suite for experimental phasing.
For its first release in 2004, CRANK was shown to effectively detect and phase anomalous scatterers from single-wavelength anomalous diffraction data. Since then, CRANK has been significantly improved and many more structures can be built automatically with single- or multiple-wavelength anomalous diffraction or single isomorphous replacement with anomalous scattering data. Here, the new algorithms that have been developed that have led to these substantial improvements are discussed and CRANK's performance on over 100 real data sets is shown. The latest version of CRANK is freely available for download at http://www.bfsc.leidenuniv.nl/software/crank/ and from CCP4 (http://www.ccp4.ac.uk/).


Weaning from ventilation: does a care bundle approach work?
There has been renewed interest in weaning from mechanical ventilation in critical care since the publication of the Modernisation Agency paper in 2002. There have been many papers reporting ways of improving the weaning process but these are specific to single elements and neglect the contextual issues that influence the weaning process. Care bundles have been introduced nationally to standardise patient care and improve patient outcome. Examples in critical care are the ventilator care bundle and sepsis care bundle. However, since care bundles have become linked with targets and part of the 10 High Impact Changes there is a tendency to want to call everything a care bundle. A care bundle is a small but critical set of processes that when implemented together improve outcome. One critical care network has written a weaning care bundle. This is an example of a service improvement initiative the aim of which was to improve weaning from mechanical ventilation. This paper reviews this approach and presents results from a pilot in one teaching hospital.


The cuffless arterial blood pressure estimation based on the timing- characteristics of second heart sound.
Continuous and non-invasive monitoring of blood pressure (BP) is important to prevent hypertensive patients from stroke and heart attack. However, most of the prevalent BP devices can provide solely intermittent measurements. In this study, a novel parameter RS2, defined as the time interval from the R wave of electrocardiographic (ECG) signal to the peak of second heart sound of phonocardiographic (PCG) signal, was used for BP estimation. Experiment was conducted on 66 normal and 19 abnormal subjects during resting condition. The results of this study showed that estimation error of systolic BP (SBP) and diastolic BP (DBP) was 2.0+/-7.5 mmHg and 0.9+/-5.1 mmHg respectively. 94.7% of the difference between measured and estimated SBPs was within +/-2 standard deviations in the Bland Altman plot. 93.4% of the difference between measured and estimated DBFs was within +/-2 standard deviations in the Bland Altman plot. The preliminary results illustrated that the RS2 is a promising parameter for continuous and non-invasive estimation of BP in homecare and mobile healthcare.


Sensitivity and specificity of piroplasm indirect fluorescent antibody test and PCR for Theileria annulata infection in clinically asymptomatic large ruminants using Bayesian latent class analysis.
There is limited information about the accuracy of molecular and serological diagnostic assays for tropical theileriosis in asymptomatic carrier large ruminants. This study has estimated the sensitivity (Se) and specificity (Sp) of PCR and an indirect fluorescent antibody test (IFAT) in the diagnosis of tropical theileriosis in cattle and buffaloes via a Bayesian latent class analysis (BLCA) framework. Blood samples were collected from 70 cattle and water buffaloes (Bubalus bubalis) raised under a smallholder production system in different Egyptian localities. T. annulata infection status was detected by PCR, and IFAT and the test results were subjected to BLCA without assuming the existence of a reference test. Our findings showed that the performance of PCR was superior to that of IFAT. PCR showed a higher Se [0.83 (95% PCI: 0.63-0.98)] in comparison to IFAT [0.72 (95% PCI: 0.68-0.75)]. Similarly, PCR showed a higher Sp [0.95 (95% PCI: 0.77-1.00)] than IFAT [0.82 (95% PCI: 0.80-0.84)]. Se and Sp of the two tests did not differ by species implying that the diagnostics' performance for T. annulata infection in bovines is the same regardless of the species under consideration. In conclusion, PCR outperforms IFAT in the detection of T. annulata infection and can thus be applied to routine control of tropical theileriosis in endemic situations where cattle and buffaloes are kept under traditional smallholder production systems.


Cranioplasty After Severe Traumatic Brain Injury: Effects of Trauma and Patient Recovery on Cranioplasty Outcome.
In patients with severe traumatic brain injury (sTBI) treated with decompressive craniectomy (DC), factors affecting the success of later cranioplasty are poorly known. We sought to investigate if injury- and treatment-related factors, and state of recovery could predict the risk of major complications in cranioplasty requiring implant removal, and how these complications affect the outcome. A retrospective cohort of 40 patients with DC following sTBI and subsequent cranioplasty was studied. Non-injury-related factors were compared with a reference population of 115 patients with DC due to other conditions. Outcome assessed 1 day before cranioplasty did not predict major complications leading to implant removal. Successful cranioplasty was associated with better outcome, whereas a major complication attenuates patient recovery: in patients with favorable outcome assessed 1 year after cranioplasty, major complication rate was 7%, while in patients with unfavorable outcome the rate was 42% (p = 0.003). Of patients with traumatic subarachnoid hemorrhage (tSAH) on admission imaging 30% developed a major complication, while none of patients without tSAH had a major complication (p = 0.014). Other imaging findings, age, admission Glasgow Coma Scale, extracranial injuries, length of stay at intensive care unit, cranioplasty materials, and timing of cranioplasty were not associated with major complications. A successful cranioplasty after sTBI and DC predicts favorable outcome 1 year after cranioplasty, while stage of recovery before cranioplasty does not predict cranioplasty success or failure. tSAH on admission imaging is a major risk factor for a major complication leading to implant removal.


2-Amino-8-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)imidazo[1,2-a][1,3,5]triazin-4(8H)-one monohydrate, a 2'-deoxyguanosine analogue with an altered Watson-Crick recognition site.
The title compound, C(10)H(12)FN(5)O(4).H(2)O, shows an anti glycosyl orientation [chi = -123.1 (2) degrees]. The 2-deoxy-2-fluoroarabinofuranosyl moiety exhibits a major C2'-endo sugar puckering (S-type, C2'-endo-C1'-exo, (2)T(1)), with P = 156.9 (2) degrees and tau(m) = 36.8 (1) degrees , while in solution a predominantly N conformation of the sugar moiety is observed. The conformation around the exocyclic C4'-C5' bond is -sc (trans, gauche), with gamma = -78.3 (2) degrees. Both nucleoside and solvent molecules participate in the formation of a three-dimensional hydrogen-bonding pattern via intermolecular N-H...O and O-H...O hydrogen bonds; the N atoms of the heterocyclic moiety and the F substituent do not take part in hydrogen bonding.


Macrophage--T-lymphocyte interaction in lichen planus. An electron microscopic and immunocytochemical study.
Papular lichen planus lesions from 12 patients were studied by a double-step immunocytochemical method to detect T-lymphocytes. Semithin sections were studied by light microscopy and ultrathin sections examined by electron microscopy. In the dermal infiltrate, many T-lymphocytes appeared closely juxtaposed to macrophages or Langerhans cells, frequently arranged in a rosette-like pattern. In the epidermis, T-lymphocytes were juxtaposed to macrophages or Langerhans cells and to degenerated keratinocytes. The close relationship between T-lymphocytes, macrophages or Langerhans cells and degenerated keratinocytes supports the hypothesis that lichen planus is immunological in nature: T-lymphocytes, after interacting with macrophages or Langerhans cells, become cytotoxic for keratinocytes.


Surface modification of the cellulose nanocrystals through vinyl silane grafting.
Incompatibility of nanocellulose with non-polar polymer matrices disrupts the interfacial interaction and results in aggregation and phase separation. In this study a facile and environmentally friendly method was used to partially substitute the surface hydroxyl groups by attaching polysiloxane to impart hydrophobic properties. The silanization reaction proceeded with hydrolysis of triethoxyvinylsilane (TEVS) into reactive silanols followed by condensation to form the branched polymer. These polysiloxane oligomers were chemically grafted to form alkoxy silane bonds on the surface of CNCs. A suitable degree of hydrophilic-hydrophobic balance of the modified CNCs was achieved which improved their dispersion in hydrophobic matrix poly(butylene adipate-co-terephthalate) (PBAT). FTIR, NMR (13C and 29Si) and XPS demonstrated successful surface chemical modification and confirmed extent of silanization as a function of silane concentration. XRD showed successful grafting of the vinyl silane agent and confirmed polymorph structure of the nanocellulose was retained. The results from TEM and AFM demonstrated successful coating of nano whiskers at 5 wt% silane loading. The successful grafting of the silane agent with pendant vinyl groups improved surface hydrophobicity. These results show that this facile method produces adequately surface modified CNC which can be used as filler in hydrophobic matrices of bioplastics.


Failure of a predictive scale in identifying patients who may benefit from a pain management program: follow-up data.
A 7-item scale to identify patients who may benefit from a pain management program was prospectively studied. The patient group consisted of 217 patients. The duration of follow-up was 2-3 years. Although an item-by-item analysis revealed some differences between successes, partial successes, and failures, the overlap was such that the total score was not predictive of outcome. Although this finding precludes clinical use of the 7-item scale in its present form, future modifications are suggested that may improve its predictive ability.


Pheromone receptor evolution in the cryptic leafroller species, Ctenopseustis obliquana and C. herana.
How new mate recognition systems evolve when changes are required in both the male and female components remains a conundrum. Here, we investigated the molecular basis of pheromone reception in two species of tortricid (leafroller) moth, Ctenopseustis obliquana and C. herana. Male C. obliquana are attracted to a 90:10 blend of (Z)-8-tetradecenyl acetate (Z8-14:OAc) and (Z)-5-tetradecenyl acetate (Z5-14:OAc), whereas C. herana males are attracted to Z5-14:OAc alone. We used a transcriptome sequencing approach from adult male and female antennae to identify 47 olfactory receptors (ORs) from each species and assessed their expression levels in male and female antennae using RNA-Seq counting and quantitative RT-PCR. Three male-biased and one female-biased OR were identified in C. obliquana by quantitative RT-PCR, and four male-biased and one female-biased receptor in C. herana. The male-biased receptors, CoblOR7, CoblOR30, CherOR7, CherOR30, CherOR1a and CherOR1b were tested for their ability to respond to sex pheromone components in a HEK293 cell calcium assay. CoblOR7 and CherOR7 responded to Z8-14:OAc, however, no receptor for Z5-14:OAc was identified. In addition to Z8-14:OAc, CherOR7 also responded to Z7-14:OAc, indicating that this receptor may be under relaxed constraint. Of the 29 amino acid differences between CoblOR7 and CherOR7, significantly more are located in the third and the sixth transmembrane domain regions. Overall, these findings are consistent with studies revealing the presence of neurons tuned to both Z8-14:OAc and Z5-14:OAc in both species, but that for C. herana males, the ability to detect Z8-14:OAc is currently not required.


Increasing the donor pool reduces the severity of liver disease: lessons learned from São Paulo, Brazil.
A new liver allocation system driven by the model for end-stage liver disease (MELD) score was implemented in Brazil in 2006. In association with the new allocation policy, there was a concomitant expansion of the number of donors. We designed this study to assess whether a potential expansion of the donor pool with these educational campaigns had reduced the severity of liver disease at transplantation. We retrospectively reviewed the state of São Paulo liver transplant database from July 2003 through July 2009. Patients were divided into groups: those who were transplanted before (pre-MELD group) and those who were transplanted after (post-MELD group) the implementation of the MELD system. The number of transplantations and the severity of liver disease were the endpoints of the study. There has been a significant shift towards an older donor population, mainly those who are dying of cerebrovascular accidents. The average MELD score has changed over time. Approximately one quarter of the patients have been transplanted with a MELD score of more than 30 in the post-MELD era. However, this number has decreased over the past 3 years (P = .012). Currently, it has been possible to transplant patients with a MELD score from 25 to 30. The number of transplantations due to hepatocarcinoma (HCC) has increased 8-fold. An aggressive educational campaign has successfully expanded the donor pool with a concomitant yearly reduction of the average MELD score at the time of transplantation. Patients with HCC have been benefited tremendously with the new allocation system.


Multiomic analyses of two sorghum cultivars reveals the change of membrane lipids in their responses to water deficit.
Drought is one of the main abiotic stresses influencing crop production all over the world. Membranes are sensitive to drought stress and easy to be degraded and modified. Lipidome and transcriptome analyses were applied to analyze the responses of membrane lipids to drought stress in two sorghum (Sorghum bicolor (L.) Moench) cultivars, drought-sensitive cv. Hongyingzi and drought-tolerant cv. Kangsi. In total, 156 lipid compounds were identified and the contents of the predominant ones changed significantly under drought stress. Drought significantly decreased the unsaturation indices (UI) of digalactosyl-diacylglycerol (DGDG), monogalactosyl-diacylglycerol (MGDG), phosphatidylglycerol (PG) and phosphatidylcholine (PC) in both cultivars, except for insignificant changes of UI for DGDG in cv. Kangsi. Transcriptome sequencing analysis identified genes related to membrane lipid remodeling such as phospholipase D α1 (PLDα1), phospholipase D δ (PLDδ), and phospholipase A 2 (PLA2). By integrating transcriptome data and lipidome data, weighted gene co-expression network analysis (WGCNA) identified hub genes, transcription factors and the genes involved in lipid metabolism. Then, the protein and protein interaction (PPI) was analyzed using STRING and the possible candidate genes regulating membrane lipids under drought stress were obtained, including CCT2, CER1, DGK1, DGK5, EMB3174, KCS4, LCB2, PAH1, PLDP1, PKP-β1, and KCS11. The results from this study have the potential to accelerate the process to breed drought-tolerant sorghum lines.


Social Media Use and Perceived Social Isolation Among Young Adults in the U.S.
Perceived social isolation (PSI) is associated with substantial morbidity and mortality. Social media platforms, commonly used by young adults, may offer an opportunity to ameliorate social isolation. This study assessed associations between social media use (SMU) and PSI among U.S. young adults. Participants were a nationally representative sample of 1,787 U.S. adults aged 19-32 years. They were recruited in October-November 2014 for a cross-sectional survey using a sampling frame that represented 97% of the U.S. SMU was assessed using both time and frequency associated with use of 11 social media platforms, including Facebook, Twitter, Google+, YouTube, LinkedIn, Instagram, Pinterest, Tumblr, Vine, Snapchat, and Reddit. PSI was measured using the Patient-Reported Outcomes Measurement Information System scale. In 2015, ordered logistic regression was used to assess associations between SMU and SI while controlling for eight covariates. In fully adjusted multivariable models that included survey weights, compared with those in the lowest quartile for SMU time, participants in the highest quartile had twice the odds of having greater PSI (AOR=2.0, 95% CI=1.4, 2.8). Similarly, compared with those in the lowest quartile, those in the highest quartile of SMU frequency had more than three times the odds of having greater PSI (AOR=3.4, 95% CI=2.3, 5.1). Associations were linear (p<0.001 for all), and results were robust to all sensitivity analyses. Young adults with high SMU seem to feel more socially isolated than their counterparts with lower SMU. Future research should focus on determining directionality and elucidating reasons for these associations.


Treatment outcomes and dental anxiety in 18-year-olds with MIH, comparisons with healthy controls - a longitudinal study.
In a previous study, 9-year-old children with severe Molar Incisor Hypomineralization (MIH) had undergone dental treatment of their first molars nearly ten times as often as children in a control group. They also showed more management problems (BMP) and fear and anxiety (DFA). To assess the long-term outcomes of dental treatments, dental anxiety, and patients' satisfaction in adolescents with MIH. Sixty-seven patients, identical with those in the baseline study, were studied at age 18-years. The participants answered the Children's Fear Survey Schedule - Dental Subscale the Dental Visit Satisfaction Scale (DVSS). Data were compiled from the dental records concerning dental health, number of restorative treatments and BMP. Molar Incisor Hypomineralization group had a significantly higher DMFT, and had undergone treatment of their permanent first molars 4.2 times as often as the controls. BMP was still significantly more common in the MIH group. However, DFS was reduced in MIH group and increased in the control groups. The DVSS scores did not differ between the groups. Conclusions. Patients with severe MIH had a poorer dental health and were still more treatment consuming at age 18-years. However, their dental fear was now at the same level as the controls.


Intramural oesophageal cyst with massive mediastinal bleeding. A case report.
Intramural oesophageal cysts lined by ciliated columnar epithelium are considered to be lesions which are not prone to serious complications except infection. In contrast to this view, a case of intramural oesophageal cyst recently operated upon by us, in which severe mediastinal bleeding developed, is described.


Identification of genes in the phenylalanine metabolic pathway by ectopic expression of a MYB transcription factor in tomato fruit.
Altering expression of transcription factors can be an effective means to coordinately modulate entire metabolic pathways in plants. It can also provide useful information concerning the identities of genes that constitute metabolic networks. Here, we used ectopic expression of a MYB transcription factor, Petunia hybrida ODORANT1, to alter Phe and phenylpropanoid metabolism in tomato (Solanum lycopersicum) fruits. Despite the importance of Phe and phenylpropanoids to plant and human health, the pathway for Phe synthesis has not been unambiguously determined. Microarray analysis of ripening fruits from transgenic and control plants permitted identification of a suite of coregulated genes involved in synthesis and further metabolism of Phe. The pattern of coregulated gene expression facilitated discovery of the tomato gene encoding prephenate aminotransferase, which converts prephenate to arogenate. The expression and biochemical data establish an arogenate pathway for Phe synthesis in tomato fruits. Metabolic profiling and ¹³C flux analysis of ripe fruits further revealed large increases in the levels of a specific subset of phenylpropanoid compounds. However, while increased levels of these human nutrition-related phenylpropanoids may be desirable, there were no increases in levels of Phe-derived flavor volatiles.


Genome-wide association findings from the brains for dementia research cohort.
The Brains for Dementia Research (BDR) cohort (~3200) is a longitudinal clinicopathological programme, complimented with genetic analysis for the purposes of aetiological investigation into dementia. Here the data from genetic association analyses are presented from the initial collection of DNA from the BDR cohort. The aim of this study was to investigate the preliminary association signals for pathologically confirmed Alzheimer's disease samples compared to controls with no other pathology (n = 520). Genome-wide genotyping was carried out using the NeuroChip platform. Analysis utilised the standard PLINK software for association studies. Genome-wide Bonferroni significant association were observed on chr19 around the APOE/TOMM40 locus across 2 distinct linkage disequilibrium blocks. Eleven of the top 35 association signals have been identified in previous studies, in addition to an intriguing SNP association within the FPR1 gene locus. This study suggests the BDR is genetically comparable to other Alzheimer's disease cohorts and offers an independent resource to verify findings, and additional genetic data for meta-analyses.


A Cross-sectional Review of Cardiothoracic Surgery Department Chairs and Program Directors.
Departmental leadership, namely the chair and program director, are sought after positions among academic cardiothoracic surgeons. However, the path to achieving these positions remains unclear. This study sought to characterize the demographics, educational pathways, and career trajectories of current cardiothoracic academic leaders in the United States. A comprehensive list of ACGME accredited thoracic surgery residency and fellowship programs was obtained. Department chairs and program directors were identified for each program from May to June 2019. For each surgeon, demographic data, education, and training institutions were identified. Information was obtained primarily using institutional based websites. A total of 72 department chairs or division chiefs and 77 program directors were identified. A minority of chairs and program directors were female (4.2%, 10.4%) or had PhD degrees (4.2%, 6.5%). A large number of surgeons trained in the North East region (35%), with Brigham and Women's hospital being the most common training institution (8%). Few chairs (31%) and program directors (39%) hold leadership positions at the institution at which they trained, however a larger proportion (52.8%, 58.4%) remain or return to the same region. Finally, 34.7% of chairs and 32.5% of program directors had some institutional exposure to where they currently practice, through medical school or training. Cardiothoracic department chairs and program directors represent an important group of surgical leaders within our evolving field. As we better understand this group of surgeon-leaders, young trainees and junior faculty that aspire for leadership positions may have a clearer idea of the path to these positions.


Chronic heat stress weakened the innate immunity and increased the virulence of highly pathogenic avian influenza virus H5N1 in mice.
Chronic heat stress (CHS) can negatively affect immune response in animals. In this study we assessed the effects of CHS on host innate immunity and avian influenza virus H5N1 infection in mice. Mice were divided into two groups: CHS and thermally neutral (TN). The CHS treatment group exhibited reduced local immunity in the respiratory tract, including the number of pulmonary alveolar macrophages and lesions in the nasal mucosa, trachea, and lungs. Meanwhile, CHS retarded dendritic cells (DCs) maturation and reduced the mRNA levels of IL-6 and IFN-β significantly (P < .05). After the CHS treatment, mice were infected with H5N1 virus. The mortality rate and viral load in the lungs of CHS group were higher than those of TN group. The results suggest that the CHS treatment could suppress local immunity in the respiratory tract and innate host immunity in mice significantly and moderately increased the virulence in H5N1-infected mice.


Anatomical observation and significance of the parietal foramen in Chinese adults.
This study aimed to investigate the incidence, number, diameter, and relative location of the parietal foramen (PF) as well as communication of intracranial and extracranial orifices and their direction, and sagittal suture morphology and length. A total of 280 dry Chinese adult skull specimens from the Department of Anatomy, Southern Medical University, were observed and measured. The occurrence rate and quantity of the PF near the sagittal suture were recorded. The aperture of the PF, the vertical distance between PF and sagittal suture, and the linear distance between PF and lambda were measured using a Vernier calliper. The length of the sagittal suture was measured by a flexible ruler; the direction and communication of intracranial and extracranial orifices were detected using a probe. The total incidence of the PF was 82.86%, slightly higher on the right side than on the left side. The single-foramen type was the most prevalent. The mean diameter of the PF on the left and right sides were 1.02 ± 0.72 mm and 1.07 ± 0.67 mm, respectively, and the diameter of the PF on the sagittal suture was 1.77 ± 0.44 mm. The mean vertical distance between the PF and the sagittal suture was 5.90 ± 2.78 mm and 5.85 ± 2.75 mm on the left and right sides, respectively. The shape of the sagittal suture in the PF area was primarily dentate shaped, with an average arc length of χ = 124.36 ± 7.76 mm, of which the majority were completely healed type. The intracranial and extracranial communication was 39.97%, and the majority of the PF were anteromedial direction. The current study provided an anatomical basis for imaging diagnosis and neurosurgery by investigating the incidence, diameter, and relative location of the PF and intracranial and extracranial communication and direction.


The Proximal Tubule Toxicity of Immunoglobulin Light Chains.
Plasma and B cells dyscrasias that overproduce monoclonal immunoglobulin free light chains (FLCs) affect the kidney frequently in various ways. The hematologic dyscrasia responsible for the production of FLCs may or may not meet the criteria for cancer, such as multiple myeloma (MM) or lymphoma, or may remain subclinical. If there is overt malignancy, the accompanying kidney disorder is called myeloma- or lymphoma-associated. If the dyscrasia is subclinical, the associated kidney disorders are grouped as monoclonal gammopathy of renal significance. Glomeruli and tubules may both be involved. The proximal tubule disorders comprise a spectrum of interesting syndromes, which range in severity. This review focuses on the recent insights gained into the patterns and the mechanisms of proximal tubule toxicity of FLCs, including subtle transport disorders, such as proximal tubule acidosis, partial or complete Fanconi syndrome, or severe acute or chronic renal failure. Histologically, there may be crystal deposition in the proximal tubule cells, acute tubule injury, interstitial inflammation, fibrosis, and tubule atrophy. Specific structural alterations in the V domain of FLCs caused by somatic hypermutations are responsible for crystal formation as well as partial or complete Fanconi syndrome. Besides crystal formation, tubulointerstitial inflammation and proximal tubulopathy can be mediated by direct activation of inflammatory pathways through cytokines and Toll-like receptors due to cell stress responses induced by excessive FLC endocytosis into the proximal tubule cells. Therapy directed against the clonal source of the toxic light chain can prevent progression to more severe lesions and may help preserve kidney function.


Improvement in the morphology of Ti-based surfaces: a new process to increase in vitro human osteoblast response.
Surface roughness has been shown to be an influencing parameter for cell response. In this experience we attempted to compare the effect of roughness organization of Ti6A14V or pure titanium substrates on human osteoblast (hOB) response (proliferation, adhesion). Surface roughness was extensively analyzed at scales above the cell size (macro-roughness) or below the cell size (micro-roughness) by calculation of relevant classic amplitude parameters (Ra, Rt) and original frequency parameters (Order, Delta). We developed a new process to prepare isotropic surfaces (electro-erosion), which were compared to isotropic surfaces obtained by polishing and anisotropic surfaces obtained by machine-tooling. The hOB response on electro-eroded (EE) Ti6A14V surfaces or pure titanium (Ti) surfaces was largely increased when compared to polished or machine-tooled surfaces after 21 days of culture. Moreover, the polygonal morphology of hOB on these EE surfaces was very close to the aspects of hOB in vivo on human bone trabeculae. By a complete description of the surface topography of EE surfaces, we concluded that when the topography was considered below the cell scale, hOB appreciated their isotropic smooth aspect, although when the topography was considered above the cell scale they appreciated their rough isotropic 'landscape' formed by many 'bowl-like nests' favouring cell adhesion and growth. Electro-erosion is a promising method for preparation of bone implant surfaces, as it could easily be applied to preparation of most biomaterials with complex geometries.


New equation to estimate resting energy expenditure in non-critically ill patients.
Correct measurement of resting energy expenditure (REE) is essential to offer a proper nutritional management during hospital stay. Dietitians are not able to perform an effective dietary treatment if predicted REE values are obtained from invalid equations. The aim of this study was to develop a more valid method to estimate REE in non-critically ill Portuguese patients. In this cross-sectional study, REE was measured by indirect calorimetry (IC) in 180 non-critically patients during hospital stay (50 participants were allocated to the validation group by simple randomization and the remaining 130 were allocated to the derivation group). The best accurate equations were derived by multiple linear regression analysis (stepwise) based on anthropometric variables. The equations were tested on the validation group and compared with published predictive equations. Data was collected from 130 patients, 68 women (52.3%) and 62 men (47.7%), mean age was 58.9 ± 16.8 years and REE-IC was 1918 ± 721 kcal/day. The new best-fit equation REE (kcal/day) = 14.4 (Height) + 52.7 (MUAC) + 453.4 (1 if male, 0 if female) - 371.2 (if Obese) - 2138.3 showed strength of evidence decisive (BF₁₀ = 8008), when compared by Bayesian model, and r2 = 0.315. Only estimated REE values obtained using new equations did not present significant difference when compared with measured REE values (kcal/kg). In this study, new equations derived from a non-critically ill population showed higher validity in estimating REE than currently used equations. A better estimation of REE may lead to a better nutritional intervention and a decreased risk of undernutrition in hospitalized patients.


SNP may modify the effect of vitamin A supplementation at birth on cytokine production in a whole blood culture assay.
Within a neonatal vitamin A supplementation (VAS) trial, we investigated the effect of VAS on TNF-α, IL-10, IL-5 and IL-13 production after lipopolysaccharide, purified protein derivative (PPD) of Mycobacterium tuberculosis and phytohaemagglutinin stimulation using a whole blood culture protocol. We found that VAS recipients had lower unstimulated TNF-α concentrations than placebo recipients. In the present paper, we investigated whether the SNP TNF-α - 308, TNF-α - 238, IL-10 - 592, IL-10 - 1082 and toll-like receptor 4 (TLR4)+896 modified the effect of VAS on cytokine production. DNA and cytokine concentrations were available from 291 children. We found a significant interaction between TNF-α - 308 genotype and VAS for the unstimulated TNF-α production (Pinteraction = 0·04); among G homozygotes, TNF-α concentrations were significantly lower after VAS compared with placebo, whereas for A carriers, VAS did not appear to have any effect. For TNF-α - 238, there was a tendency towards an increase in PPD-stimulated TNF-α production after VAS for the G homozygotes, but the opposite tendency for A allele carriers (Pinteraction = 0·07). Stratification by sex revealed a significant VAS-genotype interaction for boys for TNF-α - 238. There was a borderline-significant three-way interaction (P = 0·05) between sex, VAS and TLR4+896 genotype. Although the present study had very limited representation of the genetic variation with potential for modification of the response to VAS, it adds to the efforts of untangling the diverse effects and impact of VAS.


Seasonal changes in human hair growth.
Various parameters of hair growth were determined every 28 days for 18 months in 14 healthy Caucasian men aged 18-39 with indoor occupations in Sheffield, U.K. (latitude 53.4 degrees N). In the scalp the proportion of follicles in anagen reached a single peak of over 90% in March, and fell steadily to a trough in September. The number of shed hairs reached a peak around August/September, when least follicles were in anagen. At this time the average loss of hairs was about 60 per day, more than double that during the preceding winter. The rate of growth of the beard was lowest in January and February and increased steadily from March to July to reach a peak about 60% above the winter level. The rate of growth of thigh hair showed a similar pattern though with less pronounced differences. No seasonal fluctuations in finger- or toenail growth were detected.


Challenges in the management of colorectal cancer in low- and middle-income countries.
This narrative review aims to describe colorectal cancer (CRC) management landscape in low- and middle-income countries (LMICs), presenting the most recent and relevant papers on the topic. As a secondary aim, the authors suggest new ways of improving CRC patient care in LMICs. Several studies show that the incidence of colon cancer in low- and middle-income countries (LMICs) is rising. In addition to the increasing incidence, lack of early detection and impeded access to optimal multidisciplinary treatment may worsen survival outcomes. Developing quality diagnostic services in the proper health context is crucial for early diagnosis and successful therapy of CRC patients, and applying a resource-sensitive approach to prioritize essential treatments based on effectiveness and cost-effectiveness is key to overcoming barriers in LMICs, with clinical research collaborations between high-income countries (HICs) and LMICs being a helpful strategy to improve health indicators and prevent the burnout of health workers.


High Rate of Return to Sports and Low Recurrences With the Latarjet Procedure in High-Risk Competitive Athletes With Glenohumeral Instability and a Glenoid Bone Loss <20.
To analyze return to sports, functional outcomes, and complications following the Latarjet procedure in competitive athletes with anterior glenohumeral instability and glenoid bone loss <20%. All the included patients were operated between 2010 and 2016. The inclusion criteria were competitive athletes with anterior glenohumeral instability, a glenoid bone defect <20% who participated in contact sports, forced overhead sports, or had a previous failed Bankart repair and had a minimum 2 years' follow-up. Return to sports, range of motion (ROM), the Rowe score, and the Athletic Shoulder Outcome Scoring System score were used to assess functional outcomes. Complications and bone consolidation were also evaluated. A total of 65 athletes were included in the study. The mean follow-up was 53 months (±13), and the mean age was 23.9 years (range, 16-31 years). Overall, 94% were able to return to sports and 84% returned at the same level. No significant difference in shoulder ROM was found between preoperative and postoperative results. The Rowe and Athletic Shoulder Outcome Scoring System scores showed statistical improvement after operation (P < .001). No significant difference in shoulder ROM and functional scores was found between primary and revision cases. The total complication rate was 11% and the revision rate was 1.5% The recurrence rate was 4.6%. The bone block healed in 95% of the cases. In high-risk competitive athletes with anterior glenohumeral instability and glenoid bone loss <20%, the Latarjet procedure resulted in excellent functional outcomes, with most of the patients returning to sports and at the same level they had before injury with a low rate of recurrences. Therapeutic case series; Level of evidence, IV.