White matter connectivity in uncinate fasciculus accounts for visual attention span in developmental dyslexia.
The present study aimed to investigate the role of connectivity disruptions in two fiber pathways, the uncinate fasciculus (UF) and the frontal aslant tract (FAT), in developmental dyslexia and determine the relationship between the connectivity of these pathways and behavioral performance in children with dyslexia. A total of 26 French children with dyslexia and 31 age-matched control children were included. Spherical deconvolution tractography was used to reconstruct the two fiber pathways. Hindrance-modulated oriented anisotropy (HMOA) was used to measure the connectivity of each fiber pathway in both hemispheres. Only boys with dyslexia showed reduced HMOA in the UF compared to control boys. Furthermore, HMOA of the UF correlated with individual differences in the visual attention span in participants with dyslexia. All significant results found in HMOA of the UF were verified in fractional anisotropy (FA) of the UF using standard diffusion imaging model. This study suggests a differential sex effect on the connectivity disruption in the UF in developmental dyslexia. It also indicates that the UF may play an essential role in the visual attention span deficit in developmental dyslexia.


An Enhanced Ambulatory Surgery Experience for Patients with Cancer Through End-to-End Patient Engagement.
Ambulatory surgery centers (ASC) serve an important role for hospital systems of increasing operating capacity and offloading patient volume. When seeking to perform more complex cancer surgeries at an ASC, a systematic approach with care pathways can yield success by facilitating quick recovery for patients and reducing complication rates. End-to-end patient engagement is a key component of patient-centered care at the Josie Robertson Surgery Center and begins the moment the decision to have surgery is made and extends to the postdischarge period to track recovery. Engagement includes comprehensive education, standardization of processes, and setting clear expectations for recovery and discharge.


Comparison of humoral neuroinflammation and adhesion molecule expression in two models of experimental intracerebral hemorrhage.
Inflammatory cascades contribute to secondary injury after intracerebral hemorrhage (ICH) via humoral factors and cell-mediated cytotoxicity. Several experimental models were previously developed to analyze post-hemorrhagic neuroinflammation. However, neuroinflammatory markers have not been compared face-to-face between these models so far, and therefore, pathophysiological conclusions drawn from only one individual model may not be valid. We compared neuroinflammatory pathways in the two most common murine models: striatal injection of autologous blood or collagenase. Expression of pro- and anti-inflammatory cytokines (IL-1, TNF-α, IFN-γ, IL-6, TGF-β and IL-10) as well adhesion molecule expression (VCAM-1, ICAM-1) was analyzed by RT-PCR at several time points after ICH induction. Outcome and physiological parameters were compared between the models. Both models induced a profound and dynamic increase in the expression of pro-inflammatory cytokines and adhesion molecules. However, blood injection resulted in significantly more pronounced alteration of these markers than collagenase injection. This difference was associated with worse outcome after blood injection compared to the collagenase model despite equal ICH volumes. This is the first study performing a face-to-face comparison of neuroinflammatory pathways in the two most widely used murine ICH models, revealing substantial differences between the models. This discrepancies need to be taken into account in designing future studies employing experimental ICH models, especially when analyzing neuroinflammatory pathways and therapies.


Small RNA and degradome sequencing used to elucidate the basis of tolerance to salinity and alkalinity in wheat.
Soil salinity and/or alkalinity impose a major constraint over crop yield and quality. An understanding of the molecular basis of the plant response to these stresses could inform the breeding of more tolerant varieties. The bread wheat cultivar SR3 exhibits an enhanced level of salinity tolerance, while SR4 is distinguished by its superior tolerance of alkalinity. The small RNA and degradome sequencing was used to explore the miRNAs and corresponding targets associated with the superior stress tolerance of the SR lines. An examination of the small RNA content of these two closely related lines revealed the presence of 98 known and 219 novel miRNA sequences. Degradome libraries were constructed in order to identify the targets of the miRNAs, leading to the identification of 58 genes targeted by 26 of the known miRNAs and 549 targeted by 65 of the novel ones. The function of two of the stress-responsive miRNAs was explored using virus-induced gene silencing. This analysis indicated that regulation mediated by both auxin and epigenetic modification can be important in determining both salinity and alkalinity tolerance, while jasmonate signaling and carbohydrate metabolism are important for salinity tolerance, as is proton transport for alkalinity tolerance.


Interpersonal Media and Face-to-Face Communication: Relationship with Life Satisfaction and Loneliness.
Framed by need to belong theory, this study considers the role of communication modality, geographic proximity, and the number of close relationship partners to predict life satisfaction and loneliness. A quota sample of American adults (N = 1,869) completed four name generation tasks to identify up to 16 alters, resulting in four alters per participant (n = 7,471). Participants reported the frequency with which they communicated with each alter in the past year in person and through eight interpersonal media. Results suggest that number of relationship partners and frequency of face-to-face interaction were robust predictors of life satisfaction and loneliness. Those living alone faced significant threats to well-being. Video chat and voice call frequency were also associated with greater life satisfaction. Mediation analyses showed voice call frequency was indirectly associated with less loneliness through greater relationship maintenance satisfaction, while lean media was indirectly associated with greater loneliness through relationship maintenance frustration. The online version contains supplementary material available at 10.1007/s10902-022-00581-8.


CCCTC-binding factor controls its own nuclear transport via regulating the expression of importin 13.
CCCTC-binding factor (CTCF), a multivalent zinc-finger protein, is involved in different aspects of regulation including promoter activation or repression, gene silencing, chromatin insulation, gene imprinting, X-chromosome inactivation, cell growth or differentiation and tumor genesis. However, the molecular mechanisms of CTCF nuclear import remains unclear. In this study, we showed that the expression of CTCF influenced the intracellular distribution of itself, which might go through transport receptor - import 13 (IPO13). We further confirmed that there is a CTCF target site in ipo13 -774∼-573 bp promoter region and CTCF regulates the expression of IPO13. Besides, GST pull-down and Co-IP experiments demonstrated that CTCF interacts with IPO13. Immunofluorescence staining showed that IPO13 influenced intracellular distribution of CTCF. In all, we conclude that CTCF regulates the expression of IPO13, which, in turn, mediates the nuclear import of CTCF.


DuP 753, a nonpeptide angiotensin II-1 receptor antagonist, alters dopaminergic function in rat striatum.
The purpose of this study was to determine if the nonpeptide angiotensin II-1 receptor antagonist DuP 753 after, acute or chronic administration in vivo or after in vitro exposure, altered indices of dopaminergic function in rat striatum. In vivo studies examined the effect of acute and chronic 21-day administration of DuP 753 (10 mg/kg, s.c.) on levels of dopamine (DA) and its metabolite, dihydroxyphenylacetic acid (DOPAC). To determine if chronic treatment with DuP 753 was able to inhibit the pressor response to angiotensin II, a single i.v. dose of angiotensin II (0.1 microgram/kg) was administered 18 hours after the last dose of DuP 753. Acute DuP 753 resulted in significantly decreased (14%) levels of DA. Chronic DuP 753 resulted in increased (1.64 fold) levels of DOPAC, although DA levels were not altered. The single i.v. administration of angiotensin II resulted in increased (88%) DOPAC levels regardless of chronic DuP 753. The in vitro effect of DuP 753 (0.1 nM-1.0 microM) on basal and field stimulation-evoked release of DA and DOPAC was determined in superfused striatal slices from drug naive rats. DA was not detected in these experiments. DuP 753 did not alter basal outflow of DOPAC. At low concentrations (1.0-10 nM), DuP 753 decreased (53%) stimulation-evoked DOPAC overflow; however, at concentrations greater than 10 nM, the inhibitory effect was diminished. Nomifensine (10 microM; a DA uptake inhibitor) was included in the superfusion buffer in order to measure the effect of DuP 753 on the concentration of DA in superfusate. DuP 753 had no effect on basal DA and DOPAC outflow.(ABSTRACT TRUNCATED AT 250 WORDS)


Antimicrobial and anti-biofilm activities of bio-inspired nanomaterials for wound healing applications.
Chronic wounds are ubiquitously inhabited by bacteria, and they remain a challenge as they cause significant discomfort and because their treatment consumes huge clinical resources. To reduce the burden that chronic wounds place upon both patients and health services, a wide variety of approaches have been devised and investigated. Bioinspired nanomaterials have shown great success in wound healing when compared to existing approaches, showing better ability to mimic natural extracellular matrix (ECM) components and thus to promote cell adhesion, proliferation, and differentiation. Wound dressings that are based on bioinspired nanomaterials can be engineered to promote anti-inflammatory mechanisms and to inhibit the formation of microbial biofilms. We consider the extensive potential of bioinspired nanomaterials in wound healing, revealing a scope beyond that covered previously.


Reproducibility of plasma glucose responses to moderate-intensity exercise in individuals with type 1 diabetes.
To examine the within-person variability in plasma glucose responses to moderate-intensity morning exercise in young individuals with type 1 diabetes after overnight fasting and under basal insulin conditions. In this pilot study, eight participants completed 40 min of moderate-intensity exercise at 60% V̇O2 peak on three separate days. The within-person standard deviation (SDw) in plasma glucose response was analysed both during and 1 h after exercise using the two visits per participant most closely matched by pre-exercise plasma glucose level. When the two closest matched visits per individual were included for analysis, mean (±SD) change in plasma glucose level was -1.8 ± 1.1 mmoL/L during exercise and -0.6 ± 1.0 mmoL/L during recovery, with the SDw of these changes being 0.5 mmol (95% CI 0.2, 0.8) during exercise and 0.8 mmoL/L (95% CI 0.4, 1.3) during recovery. The median intra-individual difference in plasma glucose level change was 0.3 mmoL/L [IQR 0.1, 0.7] during exercise and 0.8 mmoL/L [IQR 0.4, 1.0] during recovery. Within-person plasma glucose responses to moderate-intensity exercise may be reproducible under fasting and basal insulin conditions and similar pre-exercise plasma glucose levels. This finding may assist the design of future studies investigating both the reproducibility of glycaemic responses to exercise and blood glucose management for individuals with type 1 diabetes.


Factors associated with knowledge of health care workers toward COVID-19 in health facilities West Guji zone, Southern Ethiopia, 2020.
Coronavirus pandemic puts healthcare workers (HCWs) at high risk and challenges the abilities of healthcare systems to respond to the crisis. This study aimed to assess the level of knowledge of HCWs and associated factors in West Guji zone public health facilities in southern Ethiopia. A health facility-based quantitative cross-sectional study was undertaken from June 10 to July 10, 2020. Two hundred and eighty-three HCWs were involved in the study using a systematic sampling method. The instrument was pretested on 5% of the sample in Yabello Hospital. Data were analyzed using bivariate and multivariate logistic regression. The HCW who had good knowledge was 84.7%. HCWs who had degree holders, masters and above holders, work experience of 2-4 years, and >4 years of experiences, had training on Coronavirus, and medical diseases were significantly associated with good knowledge of Coronavirus. This study indicated that HCWs' knowledge about the Coronavirus was good. Improving the educational status of HCWs and giving updated training on the Coronavirus will improve HCW's knowledge of the Coronavirus.


Comparison of atlas-based and deep learning methods for organs at risk delineation on head-and-neck CT images using an automated treatment planning system.
To investigate the performance of head-and-neck (HN) organs-at-risk (OAR) automatic segmentation (AS) using four atlas-based (ABAS) and two deep learning (DL) solutions. All patients underwent iodine contrast-enhanced planning CT. Fourteen OAR were manually delineated. DL.1 and DL.2 solutions were trained with 63 mono-centric patients and > 1000 multi-centric patients, respectively. Ten and 15 patients with varied anatomies were selected for the atlas library and for testing, respectively. The evaluation was based on geometric indices (DICE coefficient and 95th percentile-Hausdorff Distance (HD95%)), time needed for manual corrections and clinical dosimetric endpoints obtained using automated treatment planning. Both DICE and HD95% results indicated that DL algorithms generally performed better compared with ABAS algorithms for automatic segmentation of HN OAR. However, the hybrid-ABAS (ABAS.3) algorithm sometimes provided the highest agreement to the reference contours compared with the 2 DL. Compared with DL.2 and ABAS.3, DL.1 contours were the fastest to correct. For the 3 solutions, the differences in dose distributions obtained using AS contours and AS + manually corrected contours were not statistically significant. High dose differences could be observed when OAR contours were at short distances to the targets. However, this was not always interrelated. DL methods generally showed higher delineation accuracy compared with ABAS methods for AS segmentation of HN OAR. Most ABAS contours had high conformity to the reference but were more time consuming than DL algorithms, especially when considering the computing time and the time spent on manual corrections.


Effect of different mineral salt mixtures and dough extraction procedure on the physical, chemical and microbiological composition of Şalgam: A black carrot fermented beverage.
NaCl is utilized in Şalgam at 1-2% (w/w). The aim of this study was to reduce the NaCl content by addition of different concentrations of KCl and CaCl2 during production and evaluate their effects on quality. An innovation in production process was also employed, specifically dough extraction and use of the resulting liquid as a starter inoculum. Lactic acid bacteria (LAB) species (13) were identified using a combined approach of (RAPD)-PCR and 16S rRNA gene sequencing. Lactobacillus paracasei and Lactobacillus plantarum were dominant, but Leuconostoc mesenteroides subsp. jonggajibkimchii, Lactococcus lactis subsp. cremoris, Lactobacillus coryniformis subsp. coryniformis, Lactobacillus paraplantarum were also found. Mineral compositons were determined using ICP-OES and the most abundant were potassium, sodium, calcium, magnesium and phosphorus, respectively. A mixture of NaCl and KCl protected anthocyanin contents and improved colour parameters. Dough extraction also accelerated production of şalgam.


Sagittal Condylar Inclination and Transversal Condylar Inclination in Different Skeletal Classes.
During prosthodontic treatment, the averaged values of the transversal condylar inclination (TCI) and the sagittal condylar inclination (SCI) are used for articulator settings. This study evaluated different parameters of measurable mandibular movements according to skeletal classes. Seventy-five patients (mean age 30.8 ± 5.49) had a condylography using the Cadiax Compact device (Gamma Dental, Klosterneuburg, Austria) and cephalometric analysis performed. Statistical analysis was performed using R statistical software. There was no statistical evidence to state that the value of SCI angle is different in I compared to II Skeletal Class. There were no statistically significant differences when comparing the I vs. III and II vs. III Skeletal Class. The lowest mean SCI angle values were found in subjects with Skeletal Class III. There were statistically significant differences in left-sided TCI between Class I and II. There was a statistically significant linear relationship between ANB angle value and SCI value. Due to the wide individual variation in SCI and TCI values, it is advisable to use individual measurable parameters of mandibular movements during prosthetic reconstructions. The statistically significant relationship between SCI and ANB angle can be used to individualize the articulating parameters, especially in significant skeletal disproportions.


Pericapsular nerve group block in hip surgery. An alternative that goes beyond what we know?
Hip fracture is a pathology usually observed in older patients, prone to complications and increased morbidity and mortality during hospital admission. The PENG (Pericapsular Nerve Group) block has recently been described to provide higher quality analgesia, favoring early ambulation. The literature search was carried out from November 2018 to July 2021 with the following keywords: pericapsular nerve group block and PENG block. Studies conducted in the pediatric population or in adults with an indication other than hip surgery were excluded; obtaining 18 articles to read in full text. The analyzed studies had positive results in favor of performing the PENG block in hip surgery. Unfortunately, the current evidence is insufficient to be able to integrate the results obtained and draw conclusions about the effectiveness and safety of the PENG block.


Predictors of Recurrent Ischemic Stroke in Obese Patients With Type 2 Diabetes Mellitus: A Population-based Study.
Diabetes and obesity are established risk factors for stroke. The current study aimed to assess risk factors of ischemic stroke recurrence in diabetic patients based on their body mass index (BMI). A total of 4005 diabetic patients who had a history of ischemic stroke were identified in a retrospective cross-sectional dataset from the Malaysian National Neurology Registry. Patients were classified based on BMI, and multivariable regression analysis was used to evaluate the association between risk factors and recurrent ischemic stroke. Among obese patients, those with ischemic heart disease (aOR, 1.873; 95% CI, 1.131-3.103), received formal education (aOR, 2.236; 95% CI, 1.306-3.830), and received anti-diabetic medication (aOR, 1.788; 95% CI, 1.180-2.708) had a higher stroke recurrence risk, while receiving angiotensin receptors blockers (aOR, 0.261; 95% CI, 0.126-0.543) lowered the odds of recurrence. Overweight patients with hypertension (aOR, 1.011; 95% CI, 1.002-1.019) for over 10 years (aOR, 3.385; 95% CI, 1.088-10.532) and diabetes prior to the first stroke (aOR, 1.823; 95% CI, 1.020-3.259) as well as those received formal education (aOR, 2.403; 95% CI, 1.126-5.129) had higher odds of stroke recurrence, while receiving angiotensin-converting enzyme inhibitors (aOR, 0.244; 95% CI, 0.111-0.538) lowered the recurrence risk. Normal weight East Malaysians (aOR, 0.351; 95% CI, 0.164-0.750) receiving beta-blockers (aOR, 0.410; 95% CI, 0.174-0.966) had lower odds of stroke recurrence. Ischemic heart disease, hypertension, receiving anti-hypertensive agents, and educational level were independent predictors of recurrent stroke in obese patients. Managing the modifiable risk factors can decrease the odds of stroke recurrence.


Functional demarcation of the Fusarium core trichothecene gene cluster.
Many Fusarium species produce toxic sesquiterpenoids known as trichothecenes, including deoxynivalenol and nivalenol by Fusarium graminearum and T-2 toxin by Fusarium sporotrichioides. These toxins are potent inhibitors of protein synthesis and are a significant agricultural problem due to their adverse affect on human, animal, and plant health. Previously, 10-12 co-regulated orthologous genes within a 26-kb region were identified in F. graminearum and F. sporotrichioides, respectively. A majority of these clustered genes have been shown to be involved in different aspects of trichothecene metabolism including 7 of 15 biosynthetic steps. Three other biosynthetic steps are carried out by genes located elsewhere in the genome. In this study, we sequenced 14-16 kb of DNA on both sides of the core clusters and identified 12 new ORFs in both Fusarium species. Although the predicted functions of some of the new ORFs are consistent with some unassigned biochemical reactions, gene expression and gene deletion studies indicate that none are required for trichothecene biosynthesis. These results provide evidence to demarcate both ends of the core trichothecene gene cluster. Index descriptors: Fungal secondary metabolite, Pathogenic fungi, Gene cluster, Fusarium, Trichothecene, DON


Molecular mechanisms and imaging of lymphatic metastasis.
In many types of cancer, tumors metastasize through the lymphatic system to draining lymph nodes. These sentinel lymph nodes have gained increased attention as a prognostic indicator for the severity of the disease, leading to the sentinel lymph node mapping and biopsy procedure to be accepted as standard-of-care for breast cancer and melanoma. However, many limitations exist with this procedure resulting in high false negative rates. In this review we highlight the new advances in the understanding of the molecular mechanisms of lymphangiogenesis and tumor metastasis that may lead to improved strategies in the detection of the sentinel lymph nodes and therapeutic interventions to prevent further tumor spread. In addition, advances in imaging technology are allowing new approaches for anatomical mapping of lymphatic drainage patterns and molecular imaging strategies that may improve detection of metastatic tumor cells within sentinel lymph nodes.


[Degeneration of the tongue of Boops [(Boops boops L., 1758) (Teleost, Sparidae)] parasitized by Meinertia oestroides (Risso, 1826) (Isopoda, Flabellifera, Cymothoidae) (author's transl)].
Host fishes (Boops boops) parasitized by the cymothoid isopod Meinertia oestroides show an atrophied tonuge: its length and its initial weight can decrease of about 50%. These morphological variations are connected with deep histological alterations, such as: A more or less important vanishing of epidermis. A disorganization of the connective tissue, by numerous invading blood cells. A total vanishing of cargilage and a partial vanishing of bone, resulting from the lysis of their own fundamental substance.


High prevalence and incidence of HIV-1 in a counseling and testing center in the city of Itajaí, Brazil.
Itajaí is a port city in southern Brazil with one of the highest incidence and mortality rates from AIDS in the country. The prevalence and incidence of HIV infection were investigated in 1085 of 3196 new HIV-1 infection cases evaluated in the counseling and testing center of Itajaí from January 2002 to August 2008. Recent infections were assessed using the BED™, and pol region sequencing was performed in 76 samples. The prevalence ranged from 3.08% to 6.17% among women and from 10.26% to 17.36% among men. A total of 17% of infections were classified as recent, with annual incidence varying from 1.6% to 4.8 per 100 patient/year among women and from 2.05% to 8.5 per 100 patient/year among men. Pol sequences were obtained from 38 randomly recent infections selected individuals: 71% were infected by subtype C, 24% B, 2% D, and 2% F1. Among 38 subjects with established infection, 76% were subtype C, and 24% B. Transmitted drug resistance was detected in 18.4% of recent infection subjects (7.8% to nucleoside analog reverse-transcriptase inhibitors, 5.2% to non-nucleoside reverse-transcriptase inhibitors, and 5.2% protease inhibitors) and 5.2% of subjects with established infection had nucleoside analog reverse-transcriptase inhibitors resistance. The high prevalence and incidence of HIV infection in this region is unprecedented in studies involving cases evaluated in the counseling and testing centers in Brazil.


"Clickphine": a novel and highly versatile P,N ligand class via click chemistry.
[Structure: see text] A novel P,N-type ligand family (ClickPhine) is disclosed that is easily accessible using the Cu(I)-catalyzed azide-alkyne "click" cycloaddition. A diverse set of ligands was made in just three steps from readily available starting materials to give several homogeneous and a heterogeneous catalyst. Preliminary experiments show the efficacy of these ligands in the Pd-catalyzed allylic alkylation reaction.


Retracted: Prediction of Changes in Tumor Regression during Radiotherapy for Nasopharyngeal Carcinoma by Using the Computed Tomography-Based Radiomics.
[This retracts the article DOI: 10.1155/2022/3417480.].


Superficial middle temporal vein as a pivotal route to embolize dural carotid-cavernous fistulas.
Dural carotid-cavernous fistulas (DCCF) are located in the cavernous sinus wall involving the arterial feeders from the external and internal carotid arteries. The venous route usually passes through the internal jugular vein and inferior petrosal sinus (IPS) up to the pathologic shunts of the cavernous sinus. In cases of a thrombosed IPS, catheterization is not always possible because of the obstruction. Here, we report eight cases of DCCF treated with endovascular transvenous embolization via the superficial middle temporal vein (SMTV). A retrospective study involving eight patients with DCCF treated with transvenous embolization via SMTV was performed. In six patients, IPS was thrombosed. In one patient, IPS was patent, but we could not catheterize the internal jugular vein. In the other patient, because of the compartmentalization of the cavernous sinus, we could not access the anterior part of the cavernous sinus via IPS. Therefore, we performed the embolization via SMTV to occlude the shunts of the anterior part of the cavernous sinus. In all eight cases, navigating through the tortuous junction of the angular vein and superior ophthalmic vein (SOV) was possible. After transvenous catheterization of the cavernous sinus via SMTV, placement of coils resulted in complete occlusion of DCCF with clinical improvement in all eight patients. In the endovascular treatment of DCCF, the transfemoral approach via SMTV provides a pivotal route alternative to other transvenous routes. In patients with dilated SOV, catheterization of the cavernous sinus via SMTV is usually successful.


The Spectrum of Familial Pituitary Neuroendocrine Tumors.
Hereditary pituitary tumorigenesis is seen in a relatively small proportion (around 5%) of patients with pituitary neuroendocrine tumors (PitNETs). The aim of the current review is to describe the main clinical and molecular features of such pituitary tumors associated with hereditary or familial characteristics, many of which have now been genetically identified. The genetic patterns of inheritance are classified into isolated familial PitNETs and the syndromic tumors. In general, the established genetic causes of familial tumorigenesis tend to present at a younger age, often pursue a more aggressive course, and are more frequently associated with growth hormone hypersecretion compared to sporadic tumors. The mostly studied molecular pathways implicated are the protein kinase A and phosphatidyl-inositol pathways, which are in the main related to mutations in the syndromes of familial isolated pituitary adenoma (FIPA), Carney complex syndrome, and X-linked acrogigantism. Another well-documented mechanism consists of the regulation of p27 or p21 proteins, with further acceleration of the pituitary cell cycle through the check points G1/S and M/G1, mostly documented in multiple endocrine neoplasia type 4. In conclusion, PitNETs may occur in relation to well-established familial germline mutations which may determine the clinical phenotype and the response to treatment, and may require family screening.


Alpha-1 Antitrypsin Deficiency: a Rare Disease?
Commonly categorized as a rare disease, alpha-1 antitrypsin deficiency (AATD) is neither rare, when compared to many other genetic disorders, nor an actual disease, but rather a predisposition toward a wide variety of diseases. It is one of the most common genetic disorders which can lead to a spectrum of clinical manifestations, ranging from no symptoms to progressively debilitating systemic disease, most commonly affecting the lung and liver. It is therefore imperative for clinicians to recognize and be familiar with the spectrum of presentations, methods of diagnosis, and clinical management of AATD. It is also imperative for scientists to recognize the potential for progress in the management of this disorder. This review focuses on the current state of knowledge of AATD, including the wide range of presentations, diagnosis, and clinical management. In addition to the clinical implications of severe AATD, we discuss the relevance of heterozygous state with mild or moderate AATD in the development of both lung and liver disease. While our understanding of the multiple roles of alpha-1 antitrypsin (AAT) is on the rise, with appreciation of its immunomodulatory, anti-infective, and anti-inflammatory properties, this knowledge has yet to impact our ability to predict outcomes. We discuss nuances of augmentation therapy and review novel therapeutic approaches currently under investigation. With the expanding knowledge about the complexities of AAT function and its clinical relevance, and with the increasing ability to diagnose early and intervene on AATD, it should be our goal to change the perception of AATD as a correctable inherited disorder rather than a fatal disease.


Neurophysiological evaluation of pain.
Neurophysiological techniques for the evaluation of pain in humans have made important advances in the last decade. A number of features of neuroanatomy and physiology of nociception qualifies pain as a multidimensional phenomenon which is rather unique among the sensory systems and which poses a number of technical and procedural requirements for its appropriate diagnostic assessment. Various stimulation techniques to induce defined pain in humans and used in combination with the methodology of evoked electrical brain potentials and magnetic fields are presented. Most recent knowledge gathered from scalp topography and dipole source analysis of pain-relevant evoked potentials and fields is discussed. Particular emphasis is put upon laser-evoked potentials and their application for diagnosis, pathophysiological description and monitoring of patients with neurological disorders and abnormal pain states. Future perspectives in this growing field of research are discussed briefly.


Outpatient Autologous Stem Cell Transplants for Multiple Myeloma: Analysis of Safety and Outcomes in a Tertiary Care Center.
Autologous stem cell transplant (ASCT) is the preferred consolidation strategy to treat eligible patients with multiple myeloma (MM) and related plasma cell dyscrasias. Given the increasing volume of patients and longer wait time, outpatient ASCT for MM is the standard of care at the Vancouver General Hospital. Patients with MM, POEMS syndrome, and amyloidosis undergoing ASCT were included in this analysis. We analyzed patient characteristics, the number of patients requiring admission, duration of admission, 30-day and 100-day mortality, and overall survival. Between January 2007 and June 2016, 724 patients underwent 752 ASCTs. Of these, 702 were first ASCTs, 44 were second, and 6 were third. The median age was 60 years (interquartile range [IQR], 54-65 years). Reasons for ASCTs were MM (96.9%) amyloidosis (2.4%), and POEMS syndrome (0.7%). There were 431 (59.5%) males in this group. The median time from diagnosis to transplant was 5 months. Conditioning was melphalan 200 mg/m2 for 89.6% of the patients. Admission to the inpatient ward was required by 245 (32.6%) patients within the first 30 days. The median time to admission was 9 days post-transplant (IQR, 5-13 days). The median duration of admission was 6 days (IQR, 3-9 days). The day 100 all-cause mortality rate was 0.9%, and transplant-related mortality was 0.4%. Outpatient ASCT is a safe and feasible treatment strategy with low transplant-related mortality. Overall resource utilization is significantly lower than inpatient ASCT: however, this requires a multidisciplinary approach with close follow-up.


Diagnostic performance of GM-CSF and IL-2 in response to long-term specific-antigen cell stimulation in patients with active and latent tuberculosis infection.
A simple blood test for detecting active tuberculosis (TB) could be key to this epidemic containment, given that a large proportion of patients are unable to produce sputum for testing. Currently available interferon-γ release assays (IGRAs) are inadequate to diagnose active TB, with reported pooled sensitivity and specificity both under 81%. To explore whether cytokines/chemokines other than interferon-γ in response to long-term cell stimulation could improve the ability to distinguish between different TB infection status. We prospectively enrolled subjects with newly diagnosed pulmonary TB and their household contacts in Santiago. All contacts were tested with IGRA. Peripheral blood mononuclear cells were obtained and antigen-specific stimulated for 72 h before collecting their culture supernatants. Subjects with active TB displayed markedly low cytokines/chemokines secretion upon PBMC stimulation, with lower GM-CSF being the best differentiator from IGRA(+) contacts, with 71% (95% CI 53-85) sensitivity, 86% (95% CI 65-97) specificity and AUC = 0.79 (p = 0.0003). On the other hand, when compared to the uninfected IGRA(-) contacts, higher level of IL-2 secretion was the best indicator of active TB, with 73.5% (95% CI 56-87) sensitivity, 85% (95% CI 66-96) specificity and AUC = 0.79 (p = 0.0001). No single cytokine/chemokine released upon stimulation could accurately differentiate between active TB and all TB contacts grouped together. GM-CSF and IL-2 provided the best yield to differentiate active TB from latent TB and from TB uninfected, respectively, with higher specificities than that reported for IGRAs. However, none of both resulted sensitive enough to be used as a stand-alone biomarker for active TB.


Remote sensing and spatial statistical analysis to predict the distribution of Oncomelania hupensis in the marshlands of China.
Remote sensing and spatial statistical analysis were employed to predict the distribution of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum, in the marshlands of Jiangning county in China. Surrogate indices related to environmental factors in the marshlands were derived from a Landsat 7 ETM+ image, and the relationship between environmental covariates and the density of O. hupensis was analyzed by stepwise regression models and ordinary kriging. Although stepwise regression demonstrated that O. hupensis densities of live snails in the marshlands related significantly to the modified soil-adjusted vegetation index, wetness and land surface temperature, the correlation coefficient was low (0.282). Therefore, spatial patterns of the regression residual were investigated by the semi-variogram method, and the spatial variation of O. hupensis density attributed to the spatial autocorrelation was estimated by ordinary kriging. The regression model of the snail density and ordinary kriging of its spatial variation were then combined with the aim of improving the prediction of O. hupensis. Following this approach, the prediction indeed improved considerably (0.852). Our results show that it is possible to predict the distribution of O. hupensis in these marshlands by using remotely sensed environmental indices, and that spatial statistical analyses are capable of improving prediction accuracy. These findings are of relevance for mapping and prediction of schistosomiasis japonica in China, and hence the national control programme.


mRNA expression alterations of inward rectifier potassium channels in rat brain with cholinergic impairment.
Potassium channel dysfunction has been indicated in Alzheimer's disease. In the present study, spatial memory, the activity of cortical acetylcholinesterase (AChE) and the expressions of inward rectifier potassium channels (Kir) were measured after ibotenic acid lesions of nucleus basalis magnocellularis (nbm) in rats. Expressions of Kir (Kir2.1, Kir3.1, Kir6.1 and Kir6.2) at mRNA level were assessed using reverse transcription-polymerase chain reaction. At 28 days after ibotenic acid injection, the spatial memory of rats was significantly impaired accompanied by a 32% reduction of cortical AChE activity. Furthermore, the expression of Kir6.2 was increased by 79.3% in cortex, and that of Kir6.1 was increased by 172.1% in hippocampus, while no obvious changes in the mRNA expression of Kir2.1 and Kir3.1 were detected. This study indicated that the expression of adenosine triphosphate-sensitive potassium channel was area and channel subtype specifically increased following nbm lesions.


Transition From Wild to Domesticated Pearl Millet (Pennisetum glaucum) Revealed in Ceramic Temper at Three Middle Holocene Sites in Northern Mali.
Imprints of domesticated pearl millet (Pennisetum glaucum (L.) R. Br.) spikelets, observed as temper in ceramics dating to the third millennium BC, provide the earliest evidence for the cultivation and domestication process of this crop in northern Mali. Additional sherds from the same region dating to the fifth and fourth millennium BC were examined and found to have pearl millet chaff with wild morphologies. In addition to studying sherds by stereomicroscopy and subjecting surface casts to scanning electron microscopy (SEM), we also deployed X-ray microcomputed tomography (microCT) on eleven sherds. This significantly augmented the total dataset of archaeological pearl millet chaff remains from which to document the use of the wild pearl millet as ceramic temper and the evolution of its morphology over time. Grain sizes were also estimated from spikelets preserved in the ceramics. Altogether, we are now able to chart the evolution of domesticated pearl millet in western Africa using three characteristics: the evolution of nonshattering stalked involucres; the appearance of multiple spikelet involucres, usually paired spikelets; and the increase in grain size. By the fourth millennium BC, average grain breadth had increased by 28%, although spikelet features otherwise resemble the wild type. In the third millennium BC, the average width of seeds is 38% greater than that of wild seeds, while other qualitative features of domestication are indicated by the presence of paired spikelets and the appearance of nondehiscent, stalked involucres. Nonshattering spikelets had probably become fixed by around 2000 BC, while increases in average grain size continued into the second millennium BC. These data now provide a robust sequence for the morphological evolution of domesticated pearl millet, the first indigenous crop domesticated in western Africa. The online version contains supplementary material available at 10.1007/s10437-021-09428-8.


Novelty-induced opioid analgesia in deer mice (Peromyscus maniculatus): sex and population differences.
Exposure to a new environment elicited significant, naloxone (1.0 mg/kg) reversible analgesic responses in three different populations of deer mice; Peromyscus maniculatus artemisiae from the mainland, and P. m. angustus and P. m. triangularis from small marine islands. In all cases male deer mice displayed significantly greater levels of analgesia than females. In addition, the levels of analgesia were significantly greater in the insular than in the mainland populations. These results indicate that there are substantial sex and population differences in the novelty-induced analgesia displayed by natural and laboratory populations of deer mice.


Correction: Social determinants of food group consumption based on Mediterranean diet pyramid: A cross-sectional study of university students.
[This corrects the article DOI: 10.1371/journal.pone.0227620.].


Extra-musculoskeletal manifestations driving the therapeutic decision-making in patients with Spondyloarthritis: a 12-month follow-up prospective cohort study.
The extra-musculoskeletal manifestations (EMMs) such as recurrent acute anterior uveitis (rAAU), psoriasis (Ps), and inflammatory bowel disease (IBD), are related to the Spondyloarthritis (SpA), as well as they are associated with disease activity and poor prognosis. However, there are no data addressing its relevance regarding therapeutic decision-making in clinical practice. To evaluate the impact of EMMs to drive the treatment decision-making in patients with SpA in a 12-month follow-up. SpA patients, according to the axial and peripheral ASAS classification criteria, as well as CASPAR criteria, with any active EMM, defined as main entry criteria, were included in this longitudinal cohort study. Individuals with a history of any disease or condition that could be associated with some of the studied endpoints, including neoplasms and infectious diseases, were excluded. Specific tools related to each EMM, including Psoriasis Area Severity Index (PASI), ophthalmologic evaluation, according to the Standardization of Uveitis Nomenclature (SUN) criteria, and gut complaints were used at baseline and during the 3-, 6- and 12-month of follow-up as outcomes measures over time. Descriptive and inferential analyses were used appropriately, including Pearson's correlation test, chi-squared test, and ANOVA. P value less than 0.05 was considered as significant. A total of 560 patients were enrolled, of whom 472 meet the eligibility criteria. The majority (N = 274; 59.6%) had one or more EMM related to SpA umbrella concept. Among the EMM, the one that most influenced therapeutic decision-making was psoriasis (28.5%), followed by uveitis (17.5%) and IBD (5.5%), regardless of musculoskeletal manifestations. Clinical improvement of EMMs outcomes was observed in most patients over 12-month follow-up, especially in those with rAAU and IBD (P < 0.001). Our results showed that EMMs guided the therapeutic decision-making in half of SpA patients, regardless of musculoskeletal condition, suggesting the inter-disciplinarity among the rheumatologist, ophthalmologist, dermatologist, and gastroenterologist plays a crucial role to manage them.


Discovery of antiviral SARS-CoV-2 main protease inhibitors by structure-guided hit-to-lead optimization of carmofur.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) has been targeted for the development of anti-SARS-CoV-2 agents against COVID-19 infection because Mpro processes essential viral polyproteins and plays a key role in SARS-CoV-2 replication. In this study, we report the development of novel SARS-CoV-2 Mpro inhibitors derived from carmofur, a previously identified compound that has shown moderate potency as a covalent inhibitor of SARS-CoV-2 Mpro. To employ a structure-guided drug design strategy, a putative intact binding mode of carmofur at catalytic active site of Mpro was initially predicted by docking simulation. Based on the predicted binding mode, a series of carmofur derivatives aiming to occupy the Mpro substrate binding regions were investigated for structure-activity relationship analysis. As a result, an indole-based derivative, speculated to interact with the S4 binding pocket, 21b (IC50 = 1.5 ± 0.1 μM) was discovered. Its structure was further modified and evaluated in silico by combining docking simulation, free energy perturbation calculation and subpocket interaction analysis to optimize the interactions at the S2 and S4 binding pockets. Among the newly designed novel derivatives, 21h and 21i showed the best inhibitory potencies against Mpro with IC50 values of 0.35 and 0.37 μM, respectively. Moreover, their antiviral activities were confirmed with EC50 values of 20-30 μM in the SARS-CoV-2-infected cell-based assay, suggesting that these novel Mpro inhibitors could be applied as potential lead compounds for the development of substantial anti-SARS-CoV-2 agents.


Hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated patients with exacerbation of COPD: results from the HOPE COPD Study.
Infectious exacerbations are crucial events that dictate the natural course of COPD patients. Pneumococcal vaccination has been shown to decrease incidence of community-acquired pneumonia in COPD patients. There is a paucity of data on outcomes of hospitalisation in pneumococcal-vaccinated COPD patients in comparison with unvaccinated subjects. The objectives of the present study were to evaluate the difference in hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated COPD subjects hospitalised with acute exacerbation. This was a prospective analytical study on 120 subjects hospitalised with acute COPD exacerbation. 60 patients with prior pneumococcal vaccination and 60 unvaccinated patients were recruited. Outcomes of hospitalisation such as mortality rate, need for assisted ventilation, length of hospital stay, need for intensive care unit (ICU) care and length of ICU stay were collected and compared between two groups with appropriate statistical tools. 60% of unvaccinated patients (36 out of 60) required assisted ventilation, whereas only 43.3% of vaccinated subjects (26 out of 60) needed assisted ventilation (p-value of 0.04). Most of the secondary outcomes were better in the vaccinated group. The mean±SD length of ICU stay in the vaccinated group was 0.67±1.11 days compared to 1.77±1.89 days in the unvaccinated group. The mean±SD length of hospital stay was 4.50±1.64 days and 5.47±2.03 days in the vaccinated and unvaccinated group, respectively (p-value of 0.005). COPD patients who have received prior pneumococcal vaccination have better outcomes when they are hospitalised for an acute exacerbation. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalisation with acute exacerbation.


Extended Light Absorption and Improved Charge Separation by Protonation of the Organic Ligand in a Bismuth-Based Metal-Organic Framework.
In this work, a new method to extend the light absorption and improve the photocatalytic activity of metal-organic frameworks (MOFs) with nitrogen-containing ligand is reported, namely, the protonation of nitrogen. Specifically, a protonated Bi-based MOF synthesized by a hydrothermal method (Bi-MMTAA-H, MMTAA=2-mercapto-4-methyl-5-thiazoleacetic acid) displays a wider visible light absorption than Bi-MMTAA-R with the same single-crystal structure, but synthesized by a reflux method. The redshifted light absorption was confirmed to be caused by the protonation of nitrogen in the thiazolyl ring in MMTAA. Moreover, this protonation also facilitates the charge separation and transfer and improves the photocatalytic activity of selective oxidation of α-terpinene to p-cymene. Our results provide a new idea for nitrogen-containing Bi-based MOFs to extend the light absorption and improve the photocatalytic performance.


Late-onset depression.
Clinical and biologic studies of geriatric depression are reviewed to evaluate the role of age of onset as a distinguishing parameter. The findings suggest that late-onset depressives have a different presentation, more frequent relapses, and a greater association with medical disorders, dementia, and aging-related biologic changes than early-onset geriatric depressives. Careful clinical evaluation and follow-up of late-onset depressives are suggested. Longitudinal investigations of geriatric depressed patients are needed in order to study the frequency and time of occurrence of various clinical outcomes and identify predictors of outcome in late- and early-onset geriatric depression.


Cervical length, multifetal pregnancy reduction, and prediction of preterm birth.
To evaluate the application of transvaginal sonography assessment of cervical length before fetal reduction for predicting spontaneous preterm birth in triplet gestations reduced to twins. This retrospective study was conducted at the ultrasound unit of a university-affiliated municipal hospital. The study cohort consisted of 25 women with triplet gestations following ovulation induction or assisted-reproduction techniques who underwent fetal reduction to twins. Cervical length was assessed via transvaginal sonography before fetal reduction, and data on pregnancy outcome were retrieved from maternal records and/or maternal interviews. Cervical length (mean +/- SD) at reduction was 4.0 +/- 0.85 (range: 1.2-5.5). Five women were excluded from statistical evaluation because pregnancy complications precluded spontaneous delivery. Two of 3 (67%) women with a cervical length of <3.5 cm delivered prior to 33 weeks' gestation compared with 1/17 (6%) women with a cervical length > or = 3.5 cm. This difference was statistically significant (P < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of cervical lengths <3.5 cm to predict delivery prior to 33 gestational weeks was 67%, 94%, 67%, and 94%, respectively. Measurement of cervical length in triplet pregnancies before fetal reduction provides useful predictive information on the risk for preterm delivery.


IRQN award paper: Operational rounds: a practical administrative process to improve safety and clinical services in radiology.
As part of a patient safety program in the authors' department of radiology, operational rounds have been instituted. This process consists of radiology leaders' visiting imaging divisions at the site of imaging and discussing frontline employees' concerns about patient safety, the quality of care, and patient and family satisfaction. Operational rounds are executed at a time to optimize the number of attendees. Minutes that describe the issues identified, persons responsible for improvement, and updated improvement plan status are available to employees online. Via this process, multiple patient safety and other issues have been identified and remedied. The authors believe that the process has improved patient safety, the quality of care, and the efficiency of operations. Since the inception of the safety program, the mean number of days between serious safety events involving radiology has doubled. The authors review the background around such walk rounds, describe their particular program, and give multiple illustrative examples of issues identified and improvement plans put in place.


Association of type I neurons positive for NADPH-diaphorase with blood vessels in the adult monkey corpus callosum.
Sagittal sections through the corpus callosum of adult macaque monkeys (n = 7) reveal a subpopulation of neurons positive for NADPH-diaphorase (NADPHd). These are sparsely distributed, with 2-12 neurons scored over the anterior two-thirds of the callosum (about 14 mm). Neurons are densely labeled, type 1; but on the basis of soma and dendritic morphology, these neurons exhibit distinct heterogeneity. In one subpopulation, the cell body is narrowly attenuated (7-10 μm in width). These have bipolar dendrites, extending 300-800 μm from the cell body. One or both of the dendrites is often closely associated with blood vessels and tends to be aligned dorso-ventral, perpendicular to the body of the callosum. Another subpopulation of neurons has a larger soma (typically, 15 μm × 20 μm) and more multipolar dendrites, which are not as obviously associated with blood vessels. White matter neurons positive for NADPHd have previously been observed as a transient population, most numerous during development, in the human corpus callosum, as well as in that of other species. Their persistence in the corpus callosum of adult macaques and their close association with blood vessels has not previously been reported and is suggestive of roles other than axon guidance.


Controlled ovarian hyperstimulation and transvaginal intratubal insemination as an alternative to gamete intrafallopian transfer.
To evaluate the efficacy of controlled ovarian hyperstimulation (COH) followed by intratubal insemination in the treatment of infertility. Retrospective analysis of 179 intratubal insemination trials in 78 women over a 48-month period. Reproductive endocrinology practice. Seventy-eight women, 26 to 44 years old (34 +/- 4.3 years; mean +/- SD), classified into subgroups according to diagnosis and age (< 40 or > or = 40 years). Patients underwent COH and intratubal insemination. The rates of pregnancy, delivery, spontaneous abortion, ectopic and multiple gestation, and complications were studied and analyzed statistically. Overall, there were 36 pregnancies (20.1% of 179 trials), 29 deliveries (16.2%), 5 of 36 first trimester abortions (13.9%), 2 of 36 ectopic pregnancies (5.6%), and 4 twin gestations. There were no serious complications. In 43 women < 40 years without male factor the first trial resulted in 15 pregnancies (34.9%); in 27 women < 40 years with male factor the first trial resulted in 4 pregnancies (14.8%). Male factor reduced significantly the probability of conception. In 19 women < 40 years of age with either ovarian dysfunction or infertility of unknown cause, the first trial resulted in 9 pregnancies (47.4%), which was significantly better than the 10 pregnancies achieved in the first trial in the remaining 51 women < 40 years of age. Peak serum E2 levels and number of mature follicles had a significant effect on pregnancy rates. Intratubal insemination yielded pregnancy rates comparable to those published for GIFT at reduced cost and with fewer complications.


Mechanisms of alpha-adrenergic potentiation of ventricular arrhythmias in dogs with inherited arrhythmic sudden death.
In German shepherd dogs having inherited arrhythmias and sudden death, pause-dependent arrhythmias are triggered by early afterdepolarizations (EADs) originating from left ventricular (LV) Purkinje fibers (PF). Heterogeneity of LV repolarization provides the arrhythmogenic substrate. To elucidate the mechanisms whereby alpha-adrenergic stimulation exacerbates these arrhythmias we tested the effects of phenylephrine on both arrhythmogenic trigger and substrate. We used microelectrode techniques to record action potentials from LV and right ventricular (RV) PF and from midmyocardial sections of anteroseptal, anterobasal and posterobasal LV wall of unafflicted and afflicted dogs. EADs occurred spontaneously in 8 of 12 LV PF and in no RV PF from afflicted dogs and in no PF from unafflicted dogs. In LV PF from afflicted dogs, phenylephrine (10(-9)-10(-5) M) concentration-dependently decreased membrane potential, induced abnormal automaticity at membrane potentials from -65 to -45 mV in 6 LV PF and potentiated EADs in another 6. To determine the mechanisms of membrane depolarization we studied phenylephrine effects on IK1 in voltage-clamped single LV and RV PF cells from afflicted dogs. In LV PF, phenylephrine (10(-5) M) reduced IK1 over the range of -120 to -40 mV and had no effects on RV PF. Regional heterogeneity of LV repolarization was observed in afflicted dogs only. Phenylephrine had no effects on repolarization in either group. Alpha-adrenergic stimulation exacerbates arrhythmias in afflicted dogs by increasing the arrhythmogenic trigger while leaving the substrate unchanged. Decrease in IK1 contributes importantly to alpha-adrenergic effects on LV PF.


Robot-Assisted Laparoscopic Paravaginal Repair and Sacrocolpopexy in Patients With Pelvic Organ Prolapse.
To evaluate the surgical effects of robotic paravaginal repair and sacrocolpopexy in patients diagnosed with lateral cystocele due to paravaginal defect. Robotic paravaginal repair and sacrocolpopexy were performed contemporaneously in 43 patients with high-grade pelvic organ prolapse combined with a lateral or mixed cystocele. To objectively evaluate prolapse correction, the Pelvic Organ Prolapse Quantification (POP-Q) test was performed at the 12-month visit and the results compared to those of the preoperative period. Subjective satisfaction was scored using the Patient Global Impression of Improvement (PGI-I) questionnaire. POP-Q measurement results before and after surgery, an objective indicator of surgery, the Ba and C scores improved significantly from 2.1 ± 1.2 preoperatively to -2.0 ± 1.1 postoperatively (P <.01), and from 0.3 ± 1.3 preoperatively to -4.3 ± 1.1 postoperatively (P <.01), respectively. In PGI-I questionnaire, the numbers of patients who awarded scores of 1 and 2 (evidencing high-level symptom improvement) were 33 at 1 month (76.7%), 30 at 3 months (69.8%), and 28 (65.1%) at 12 months. When respondents awarding 3 points (a little improvement) were included, the numbers rose to 38 (88.4%) at 1 and 3 months and 35 (81.4%) at 12 months, indicating satisfaction with symptom improvement. There were no critical complications during and after surgery, but complications such as de novo stress urinary incontinence that lower patient satisfaction occurred in some cases. Robot-assisted paravaginal repair and sacrocolpopexy can be safely performed in patients with cystocele-predominant pelvic organ prolapse and good surgical results can be expected with excellent effects.


Increased expression of fibronectin and the alpha 5 beta 1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia.
The extracellular matrix (ECM) is an important regulator of angiogenesis and vascular remodeling. We showed previously that angiogenic capillaries in the developing CNS express high levels of fibronectin and its receptor alpha5beta1 integrin, and that this expression is developmentally downregulated. As cerebral hypoxia leads to an angiogenic response, we sought to determine whether angiogenic vessels in the adult CNS re-express fibronectin and the alpha5beta1 integrin. Ten-week old mice were subject to hypobaric hypoxia for 0, 4, 7 and 14 days, and fibronectin/integrin expression examined. Fibronectin and the alpha5 integrin subunit were strongly upregulated on capillaries in the hypoxic CNS, with the effect maximal at the earliest time point examined (4 days). Immunofluorescent studies demonstrated that the alpha5 integrin was expressed by angiogenic endothelial cells. In light of the defined angiogenic role for fibronectin in other systems, this work suggests that induction of fibronectin-alpha5beta1 integrin expression may be an important molecular switch driving angiogenesis in the hypoxic CNS.


A comparison of oncological outcomes after abdominoperineal excision before and after the implementation of a selective perineal flap closure program.
Abdominoperineal excision (APE) is the operation chosen when a patient has low rectal cancer unamenable to sphincter preserving surgery. Perineal flap reconstruction is associated with less wound morbidity but little is known about oncological outcomes. The objective was to compare outcomes in patients undergoing APE before and after the introduction of a program that utilized flap reconstruction of the perineum. A retrospective review of a prospectively maintained database was performed. Patients who underwent APE followed by primary closure or flap reconstruction between 1998 and 2018 were selected. The cohorts were divided according to the implementation of the flap reconstruction program in July 2009. Clinicopathological data, recurrence and survival were compared between the cohorts. One hundred and forty nine patients underwent APE for rectal adenocarcinoma between 1998 and 2018. There were 57 patients in the pre-flap era and 92 in the post-flap era. Forty-six patients underwent flap reconstruction in the latter cohort (50%). More patients in the post-flap era underwent neoadjuvant chemoradiotherapy (85.9% vs. 63.2%; p < .01). Margin positivity rates decreased from 21.1% in the pre-flap era to 10.9% in the post-flap era (p = .10) and there was an associated improvement in incidence and time to local recurrence (p = .03). The use of perineal flap reconstruction is associated with a longer median time to local recurrence. Perineal flap reconstruction may contribute to reduced margin positivity.


Expression on leukemic cells and serum circulating levels of intercellular adhesion molecule-1 (ICAM-1) in B-cell chronic lymphocytic leukemia: implications for prognosis.
Expression of intercellular adhesion molecule-1 (ICAM-1) has been correlated clinical and laboratory characteristics of 62 patients with untreated CD5+ chronic lymphocytic leukemia (CLL). ICAM-1 was detected on B-CLL cells from 19 out of 62 patients (30.6%) and its expression did not correlate with the majority of immunological markers. An important finding of this study was the association between ICAM-1 expression and mean fluorescence intensity (MFI) of Slg (r = 0.507; P < 0.001). As far as correlation with clinical parameters is concerned, a statistically significant association between Binet clinical stages and ICAM-1 expression was found (P < 0.05). Furthermore, an atypical CLL morphology was more frequently encountered among patients who expressed ICAM-1 (P < 0.005). To obtain more information on the role of ICAM-1 in CLL we measured serum levels with a sandwich enzyme immunoassay. In 47 B-cell CLL patients studied, the mean value of circulating ICAM-1 levels was significantly higher (561 +/- 201 ng/ml) than that observed in 25 normal controls (353 +/- 162 ng/ml; P < 0.005); a clear correlation being found with Binet clinical stages (P = 0.026) and bone marrow (BM) histology (P < 0.005). We conclude that circulating ICAM-1 is elevated in CLL and such an increase reflects tumor mass as defined by clinical stages and BM histology, rather than peripheral blood lymphocytosis (r = 0.240). Even if soluble ICAM-1 appears to be less specifically increased that soluble CD23 serum levels, these circulating molecules were not completely independent of each other (r = 0.512; P < 0.001).


Corrigendum: (1) Some OFF Bipolar Cell Types Make Contact With Both Rods and Cones in Macaque and Mouse Retinas; (2) OFF Bipolar Cells in Macaque Retina: Type-specific Connectivity in the Outer and Inner Synaptic Layers.
[This corrects the article on p. 105 in vol. 8, PMID: 25309346.][This corrects the article on p. 122 in vol. 9, PMID: 26500507.].


Maintaining the status quo: T-cell homeostasis.
Lymphocyte numbers and subset composition are maintained at relatively constant levels throughout adulthood. Fluctuations in cell numbers due to infection, loss of cells, or other influences are smoothed out by unknown mechanisms that return the system to homeostasis. Regulation of lymphocyte numbers could be controlled at several points: rate of production, alteration in life span by diminution or enhancement of survival, or by division of cells within the compartment. Cell numbers within the immune system appear to be controlled by homeostatic mechanisms that influence each of these points. This discussion will focus on the regulation of peripheral cell numbers by the antigen-independent proliferation of T cells, which has recently been demonstrated to contribute to the maintenance and recovery of lymphocyte homeostasis.


COVID-19-related issues on tele-counseling helpline in Bangladesh.
To provide a brief description of COVID-19-related issues presented by callers to a tele-counseling helpline in Bangladesh. Counselors who receive calls write brief descriptions of each call. These descriptions were coded and analyzed. Eighty-six percent of callers displayed anxiety and/or sleeplessness; these callers also displayed a range of issues including family/interpersonal problems, financial difficulties, physical health concerns, mental illness, and difficulty managing quarantine. These findings indicate the mental health challenges faced in Bangladesh due to lockdown and can inform future interventions.


Leadless atrioventricular synchronous pacing in an outpatient setting: Early lessons learned on factors affecting atrioventricular synchrony.
Leadless pacemakers (PMs) capable of atrioventricular (AV) synchronous pacing have recently been introduced. Initial feasibility studies were promising but limited to just a few minutes of AV synchronous pacing. Real-world, long-term data on AV synchrony and programming adjustments affecting AV synchrony in outpatients are lacking. The purpose of this study was to investigate AV synchrony and influences of PM programming adjustments in outpatients with leadless VDD PMs. All patients who received a leadless VDD PM (Micra™ AV, Medtronic) between July 2020 and May 2021 at our center were included in this observational study. AV synchrony was assessed repeatedly postoperatively and during follow-up using Holter electrocardiographic (ECG) recordings. AV synchrony was defined as a QRS complex preceded by a p wave within 300 ms. The impact of programming changes during follow-up on AV synchrony was studied. A total of 816 hours of Holter ECG from 20 outpatients were analyzed. During predominantly paced episodes (≥80% ventricular pacing), median AV synchrony was 91% [interquartile range (IQR) 34%-100%] when patients had sinus rates 50-80/min. Median AV synchrony was lower when patients had sinus rates >80/min [33% (29%-46%); P <.001]. During a stepwise optimization protocol, AV synchrony could be improved (P <.038). Multivariate analysis showed that a shorter maximum A3 window end (P <.001), lower A3 threshold (P = .046), and minimum A4 threshold (P <.001) improved AV synchrony. Successful VDD pacing in the outpatient setting during higher sinus rates is more difficult to achieve than can be presumed based on initial feasibility studies. The devices often require multiple reprogramming to maximize AV sequential pacing.


The effect of intralipid on human lymphocyte and monocyte function.
Peripheral blood lymphocyte function (PHA) was unaffected by Intralipid in patients receiving lipid as part of a parenteral nutrition regime, and in volunteers receiving a small intravenous bolus. However monocyte function (chemotaxis) was significantly impaired by Intralipid in both groups. Three measures of monocyte function confirmed depression following in vitro exposure to Intralipid. Electronmicrographs of circulating monocytes and autoradiographs of cells exposed to 14C-Intralipid in vitro suggested that this detrimental effect on monocytes may follow phagocytosis of lipid particles. These findings suggest that caution should be exercised with the use of Intralipid in patients at particular risk of sepsis.


Malacoplakia of epididymis.
Malacoplakia localized to the epididymis is described. Ultrastructural study revealed the presence of bacterial bodies in phagolysosomes of malacoplakic macrophages. The possible role of the phagocytosed bacteria in the pathogenesis of malacoplakia is briefly discussed.


The effect of temperature on Triclosan and Lead exposed mussels.
Interest on the effects of emerging contaminants over aquatic organisms has increased in the last years. Nonetheless, the toxic action of classical natural and anthropogenically-driven metals has also to be monitored, especially because they reflect real environmental situations. For that, in the present study we focused on the effects on the marine mussel Mytilus galloprovincialis of the personal care product Triclosan (TCS) and Lead (Pb), as toxic metal, under separate and co-exposure situations at environmentally relevant concentrations: TCS (1 μg/L) and Pb (50 μg/L). The consideration of an additional factor such as an increase in ambient temperature was also included to provide a forecasted scenario of climate change: from the ambient temperature at actual conditions (17 °C) to a predicted warming situation (22 °C). Water chemical characterization and some physical properties and bioaccumulation of TCS and Pb in mussels at the end of the experiment (28 days) was considered. The parameters followed up comprise the energy related system production (electron transport system) and glycogen and protein reserves. Antioxidant enzymatic defences towards reactive oxygen species (ROS) and the consequences of ROS damage over endogenous lipids (LPO) and proteins (PC). Overall the results suggested only particular responses to chemical exposures at 17 °C whereas at 22 °C the detoxification machinery was set up and this prevented the occurrence of LPO. Nonetheless, PC formation occurred under Pb and TCS + Pb co-exposure at the highest temperature. Due to the complexity of the study: 4 chemical conditions, 2 temperatures and 10 biomarkers considered, a principal component ordination (PCO) analysis was included. The results of this integrative analysis confirmed a clear effect of the temperature, more responsiveness to drugs at 22 °C and in all likelihood due to Pb presence.


Bioinformatics methods for identifying candidate disease genes.
With the explosion in genomic and functional genomics information, methods for disease gene identification are rapidly evolving. Databases are now essential to the process of selecting candidate disease genes. Combining positional information with disease characteristics and functional information is the usual strategy by which candidate disease genes are selected. Enrichment for candidate disease genes, however, depends on the skills of the operating researcher. Over the past few years, a number of bioinformatics methods that enrich for the most likely candidate disease genes have been developed. Such in silico prioritisation methods may further improve by completion of datasets, by development of standardised ontologies across databases and species and, ultimately, by the integration of different strategies.


Applying systemic functional linguistics to conversations with dementia: the linguistic construction of relationships between participants.
Social isolation in dementia is a growing concern as the incidence and prevalence of dementing conditions is on the rise in many societies. Positive social interactions, which foster the construction and enactment of positive interpersonal relationships and therefore positive discursive identities, make an important contribution to emotional well-being. In this article, we investigate how two women diagnosed with dementia of the Alzheimer's type use language to relate to each other and two visiting graduate students. We use Systemic Functional Linguistics as an analytical framework, specifically investigating the use of vocatives and naming, and conversational moves and exchanges.


The LBP/BPI multigenic family in invertebrates: Evolutionary history and evidences of specialization in mollusks.
LBPs (lipopolysaccharide binding proteins) and BPIs (bactericidal permeability increasing proteins) are important proteins involved in defense against bacterial pathogens. We recently discovered a novel biocidal activity of a LBP/BPI from the gastropod Biomphalaria glabrata and demonstrated its role in parental immune protection of eggs, highlighting the importance of LBP/BPIs in invertebrate immunity. Here we characterize four additional LBP/BPI from B. glabrata, presenting conserved sequence architecture and exon-intron structure. Searches of invertebrate genomes revealed that existence of LBP/BPIs is not a conserved feature since they are absent from phyla such as arthropods and platyhelminths. Analyses of LBP/BPI transcripts from selected mollusk species showed recent parallel duplications in some species, including B. glabrata. In this snail species, LBP/BPI members vary in their expression tissue localization as well as their change in expression levels after immune challenges (Gram-negative bacterium; Gram-positive bacterium or yeast). These results, together with the predicted protein features provide evidences of functional specialization of LBP/BPI family members in molluscs.


End-of-life care in neurodegenerative conditions: outcomes of a specialist palliative neurology service.
People with advanced neurological conditions (ANCs) face complex problems and needs that are often unrecognised and undertreated.Their last year of life may be characterised by unplanned hospital admissions and an unexpected death. A National End-of-Life Care Programme (NEoLCP) 2010 framework made recommendations to aid timely and appropriate end-of-life care for people with ANCs. Assessment of key outcomes of a UK nurse-led palliative neurology service against the NEoLCP standards. A retrospective study of clinical records of patients who died from an ANC under the care of the service from December 2006 to April 2012. All 62 patients had multidisciplinary care coordinated by a key worker-a clinical nurse specialist (CNS) in palliative neurology. Mental capacity was assessed in 95% of cases, of which 95% had a documented advance care plan or best interest decision.The CNS had specific input regarding carer distress in 77% of cases. Mean hospital admissions were 0.9 per patient in the last year of life, compared with 3.5 nationally across all diagnoses. The service demonstrated better outcomes in other key areas, including place of death, with more patients dying at home or in the hospice compared with national figures. This service model fulfils key NEoLCP recommendations, as well as resulting in low hospital admissions and deaths.


[Identification of chlorzoxazone metabolites in human urine (author's transl)].
Besides 6-hydroxychlorzoxazon II, the main metabolite of 5-chlorobenzoxazolin-2-one (chlorzoxazone I, Paraflex) two other compounds were found to be metabolites of chlorzoxazone: 5-chloro-2,4-dihydroxyacetanilide XXII is produced from 6-hydroxychlorzoxazone II by ring cleavage and acetylation of the nitrogen. More interesting is the formation of the 6-hydroxybenzoxazolone XX. This compound is formally produced by substitution of Cl for hydrogen and hydroxylation of a neighbour ring-carbon atom.


Investigation of medical faculty students' views on cadaver and cadaver teaching in anatomy.
Cadaver education in anatomy is one of the cornerstones of medical school education. The primary purpose of this study is to determine the importance of cadaver education from the students' point of view by examining the effect of cadaver education on learning the anatomy course. In this study, the perspectives of second-term medical students who received or did not receive anatomy education with cadavers, on cadavers and on anatomy education with cadavers were investigated. The study was carried out with a total of 116 (66 females and 50 males) second-term medical faculty students. Participants were divided into 2 groups; the first group (n=56) consisted of students who learned anatomy with cadavers, while the second group (n=60) included students who had never seen a cadaver and learned anatomy through atlas and models. As a result, it was determined that the students in both groups thought that there should be cadavers in anatomy education and education with cadavers would accelerate and facilitate the learning process of anatomy. It was also determined that, the students who received anatomy education with cadaver were psychologically affected by the cadaver compared to those who did not, and they thought that the cadaver was less effective in gaining a physician identity (P<0.05). When the results of the study are evaluated, it is revealed that the anatomy course is difficult, but the education given on the cadaver significantly facilitates learning and makes it more attractive.


Diffusion-relaxation scattered MR signal representation in a multi-parametric sequence.
This work focuses on obtaining a magnetic resonance imaging (MRI) signal representation that accounts for a longitudinal T1 and transverse T2⋆ relaxations while at the same time integrating directional diffusion in the context of scattered multi-parametric acquisitions, where only a few diffusion gradient directions and b-values are available for each pair of echo and inversion times. The method is based on the three-dimensional simple harmonic oscillator-based reconstruction and estimation (SHORE) representation of the diffusion signal, which enables the estimation of the orientation distribution function and the retrieval of various quantitative indices such as the generalized fractional anisotropy or the return-to-the-origin probability while simultaneously resolving for T1 and T2⋆ relaxation times. Our technique, the Relax-SHORE, has been tested on both in silico and in vivo diffusion-relaxation scattered MR data. The results show that Relax-SHORE is accurate in the context of scattered acquisitions while guaranteeing flexibility in the diffusion signal representation from multi-parametric sequences.


Group B streptococci in the lower urogenital tract and late abortions.
The occurrence of group B streptococci in the lower urogenital tract of 150 women with signs of abortion and 100 women with uncomplicated pregnancy was studied. Group B streptococci appeared significantly more frequently in the urine (p less than 0.001) and in the uterine cervix (p less than 0.01) of women with abortion. Delivery resulted in 85% of patients with group B streptococci in the urine and in 42% of patients with no group B streptococci (p less than 0.001). Group B streptococci were cultured from amniotic fluid from three of eight women with intact membranes and were isolated from the urine and cervix. These bacteria were antibody coated as demonstrated by an immunofluorescence technique. Group B streptococci were recovered from blood or liver in six fetuses, including two who had group B streptococci in the amniotic fluid. The study demonstrates an association between the occurrence of group B streptococci in the urine and cervix and late abortions.


[Establishment of malaria early warning system in Jiangsu Province VI Regular surveillance of eliminating malaria and its effect].
To analyze the regular surveillance and evaluate its effect during the elimination stage of malaria in Jiangsu Province from 2012 to 2014 and discuss the best way for surveillance and management, so as to provide the evidence for formulating and adjusting the strategy and methods for malaria elimination. The data of network malaria reports, blood tests of feverish patients, epidemiology investigation forms of case study of malaria patients in the report system, and investigation and disposition forms of epidemic regions were collected and analyzed statistically. From 2012 to 2014, there were 894 malaria cases in total. Totally 1 625 034 feverish patients had blood tests, and 892 of them showed positive and the positive rate was 0.05%. The epidemiological case study showed that all the patients were foreign infection import patients except one was foreign import cases by blood transfusion. These cases were mainly distributed in Nantong City (125 cases), Yangzhou City (123 cases), Huai'an City (112 cases), Lianyungang City (111 cases) and Taizhou City (88 cases), and the total cases of the five cities accounted for 62.53% (559/894) of total cases of entire province. These cases were mainly diagnosed in country level CDC and medical organizations, and city level medical organizations. These units accounted for 87.02% of all the diagnostic organizations (778/894). From 2012 to 2014, there are no reports of local malaria infection cases in Jiangsu Province, meaning the preliminary realization of eliminating malaria. However, we still should strengthen the regular surveillance and treatment of import malaria cases.


Self-rated health status as a risk factor for future vascular events and mortality in patients with symptomatic and asymptomatic atherosclerotic disease: the SMART study.
Lower self-rated health status has been associated with worse prognosis in patients with coronary artery disease (CAD). We investigated the influence of self-rated physical and mental health status on the risk of future vascular events and mortality for various locations of symptomatic atherosclerotic disease and asymptomatic disease. Patients with CAD (n = 2547), cerebrovascular disease (n = 1061), peripheral arterial disease (PAD; n = 648), abdominal aortic aneurysm (AAA; n = 272) and asymptomatic atherosclerotic disease (n = 1933) were followed for a median of 4 years for the occurrence of a new vascular event or death. Self-rated health status was assessed with the Short Form-36 physical and mental component summary scales. Cox regression models were used to estimate associations between health status and vascular events and death, adjusted for age, sex, vascular risk factors and intima-media thickness. In the total population, lower self-rated physical health status (per 10-point decrease) increased the risk of vascular events [hazard ratio (HR) = 1.37, 95% confidence interval (CI) 1.24-1.52], and all-cause (HR = 1.45, 95% CI 1.29-1.63) and vascular mortality (HR = 1.40, 95% CI 1.20-1.64). A 10-point decrease in mental health status was associated with a modest increase in the risk of vascular events (HR = 1.19, 95% CI 1.08-1.32), and all-cause (HR = 1.19, 95% CI 1.05-1.34) and vascular mortality (HR = 1.28, 95% CI 1.09-1.49). Risk estimates of physical and mental health status were highest in patients with asymptomatic atherosclerotic disease and lowest in those with PAD. Poorer self-rated physical and mental health status increases the risk of vascular events and mortality in a broad population of patients with symptomatic and asymptomatic atherosclerotic disease.


Neurodevelopmental outcomes for children with hypoplastic left heart syndrome at the age of 5 years.
This study aimed to determine the neurodevelopmental (ND) outcome for children with hypoplastic left heart syndrome (HLHS) at early school age. English-speaking patients who underwent the Norwood procedure between 2000 and 2005 were eligible at 4-6 years of age for ND testing. Of the 72 eligible patients, 44 (61 %) agreed to participate, and 37 completed ND testing before the close of the study. Three subjects were excluded from analyses due to late stroke. The ND testing included intelligence, visual motor integration, memory and motor and language skills. Parents and teachers completed measures of behavior and attention problems. Subjects' scores and parent/teacher ratings were converted to z-scores and compared with test norms. Higher scores on child measures represent better outcomes, whereas higher scores on parent and teacher rating scales indicate more problems. The average ND performance of the tested cohort fell within one standard deviation of the test norms for all measures. However, the subjects performed significantly lower than the test norms on measures of visual-motor integration, fine motor skills, memory, and word structure (z = -0.42 to -0.54; p < 0.005). On the parent and teacher completed measures, the subjects scored higher than the test norms on attention problems (z = 0.40-0.62; p < 0.005). Although the overall ND performance of the cohort was normal, the subjects showed relative weakness in visual motor and attention skills. Ongoing developmental monitoring of these children is recommended to guide interventions that may improve individual outcomes and to assess the impact of changes in clinical management strategies on functional outcomes.


The evolving treatment of congenital heart disease in patient with Down syndrome: Current state of knowledge.
Children with Down syndrome are usually seen as not worthy of high-risk cardiac surgery. Through this review, we try to show the results of curative and palliative surgery for functional single ventricle syndrome in patients with Down syndrome, as there is currently no standard protocol for the treatment of this category of patients. An exhaustive search of all related published medical literature included the following domains: Down syndrome and diagnosis, Down syndrome and taxonomy, Down syndrome, and natural history, Down syndrome and cardiovascular abnormalities, Down syndrome and pulmonary hypertension, Down syndrome and institutionalization, Down syndrome and surgical repair, Down syndrome, and single ventricle palliation, Down syndrome and Glenn, Down syndrome, and Fontan. 12 articles were included from 775 identified. Low-risk cardiac surgery procedure should be provided for Down syndrome with a balanced ventricular septal defect. There is no universal agreement about the surgical approach for Down syndrome with unbalanced ventricular septal defects, but it can be performed at relatively low risk. TCPC in Down syndrome patients could be a relatively low-risk procedure if patients are prepared well and their pulmonary vascular resistance is low. Randomized prospective studies are required to show the long-term impact of TCPC palliation and develop a better understanding of standardized care of these patients.


Recovery Capital among Migrants and Ethnic Minorities in Recovery from Problem Substance Use: An Analysis of Lived Experiences.
Migrants and ethnic minorities (MEM) are known to be disadvantaged concerning risk factors for problem substance use and resources to initiate and sustain recovery (i.e., recovery capital). Yet, the voices of MEM are largely overlooked in recovery literature. This study explores recovery capital through 34 semi-structured interviews with a diverse sample of MEM in recovery in two ethnically diverse cities in Belgium. A Qualitative Content Analysis using recovery capital theory allowed us to identify various recovery resources on a personal, social, and community level. While physical and human recovery resources play a central role in participants' narratives, personal recovery capital is closely intertwined with meaningful social networks (i.e., social recovery capital) and recovery-supportive environments that maximize opportunities for building culturally sensitive recovery capital (i.e., community recovery capital). Though MEM-specific elements such as culture, migration background, stigma, and structural inequalities play a significant role in the recovery resources of MEM, the largely "universal" nature of recovery capital became clear. The narratives disclose a distinction between "essential" and "acquired" recovery capital, as well as the duality of some recovery resources. The need for developing recovery-oriented systems of care that are culturally responsive, diminish structural inequalities, and facilitate building recovery capital that is sensitive to the needs of MEM is emphasized.


Neurophysiological Markers Related to Negative Self-referential Processing Differentiate Adolescent Suicide Ideators and Attempters.
Adolescent suicide is a major public health concern, and presently, there is a limited understanding of the neurophysiological correlates of suicidal behaviors. Cognitive models of suicide indicate that negative views of the self are related to suicidal thoughts and behaviors, and this study investigated whether behavioral and neural correlates of self-referential processing differentiate suicide ideators from recent attempters. Adolescents with depression reporting current suicidal ideation and no lifetime suicide attempts (suicide ideators, n = 30) and past-year suicide attempts (recent attempters, n = 26) completed a self-referential encoding task while high-density electroencephalogram data were recorded. Behavioral analyses focused on negative processing bias (i.e., tendency to attribute negative information as being self-relevant) and drift rate (i.e., slope of reaction time and response type that corresponds to how quickly information is accumulated to make a decision about whether words are self-referent). Neurophysiological markers probing components reflecting early semantic monitoring (P2), engagement (early late positive potential), and effortful encoding (late late positive potential) also were tested. Adolescent suicide ideators and recent suicide attempters reported comparable symptom severity, suicide ideation, and mental disorders. Although there were no behavioral differences, compared with suicide ideators, suicide attempters exhibited greater P2 amplitudes for negative versus positive words, which may reflect enhanced attention and arousal in response to negative self-referential stimuli. There were no group differences for the early or late late positive potential. Enhanced sensory arousal in response to negative stimuli-that is, attentional orienting to semantic, emotional, and self-relevant features-differentiates adolescent suicide attempters from ideators and thus may signal risk for suicidal behavior.


Impact of carbapenem restriction on the antimicrobial susceptibility pattern of Pseudomonas aeruginosa isolates in the ICU.
Rates of carbapenem-resistant Pseudomonas aeruginosa are increasing. Aggressive prevention strategies, including instituting antimicrobial stewardship programmes, are essential for combating antimicrobial resistance. We conducted this study to compare the antimicrobial susceptibility pattern of P. aeruginosa before and after carbapenem restriction. We conducted a two-phase retrospective study in an adult ICU. The first phase was from May until July 2016 (before carbapenem restriction), whereas the second phase was from September until November 2016 (while implementing carbapenem restriction). The antimicrobial susceptibility pattern of P. aeruginosa was reviewed in August and December 2016. The measure of carbapenem-resistant P. aeruginosa was the proportion of resistant isolates (percentage resistant). The measure of antibacterial consumption in the study phases was DDDs/1000 patient days. The overall carbapenem consumption decreased significantly in the second phase, from 28.44 to 11.67 DDDs/1000 patient days (P = 0.012). The resistance of P. aeruginosa to imipenem and meropenem decreased significantly from 76.0% to 38.5% (P = 0.019) and from 74.1% to 30.0% (P = 0.012), respectively. Susceptibility of P. aeruginosa to other antibacterials was not affected by carbapenem restriction. These data suggest that restricting carbapenems, even for a short duration, may be an effective strategy for managing the problem of carbapenem resistance in P. aeruginosa.


The SCID mouse model: novel therapeutic targets - lessons from gene transfer.
The hallmark of rheumatoid arthritis (RA) is progressive destruction of the joints, preceded and accompanied by synovial hyperplasia and chronic inflammation. Spontaneous and induced animal models of RA reflect predominantly the inflammatory aspects of the disease. To reproduce the destruction of cartilage and bone mediated by an activated synovium, it was desirable to develop models that allow the dissection of cellular and molecular components derived from human tissue. The SCID mouse co-implantation model of human RA focuses on RA synovial fibroblasts (RA-SF) and their role in cartilage destruction. The model has provided the best evidence that RA-SF contribute significantly to matrix degradation, even in the absence of human lymphocytes and macrophages, since highly purified RA-SF invade the co-implanted normal human cartilage. Moreover, it became clear that they maintained their aggressive phenotype over long periods of time, particularly at sites of invasion into the co-implanted human cartilage. Targeting different signaling molecules, cytokines and matrix-degrading enzymes by soluble receptors, antagonists or negative mutants in the SCID mouse model of RA has implicated many of them in the mechanisms leading to cartilage destruction. However, since inhibition of a single molecule or pathway is not sufficient to inhibit the aggressive behavior of RA-SF it appears necessary to co-express in the synoviocytes genes for two or even more antagonists of e.g. cytokines, matrix-degrading enzymes or molecules interfering specifically with signaling pathways involved in the apoptosis of RA-SF. Based on the recent observation that the L1 (line-1) endogenous retroviral element appears responsible for the cytokine- independent activation via the MAPK p38delta, the current understanding of disease pathogenesis suggests that both the cytokine-dependent as well as the cytokine-independent pathways of joint destruction must be inhibited. Modulation of both pathways by gene transfer approaches in the SCID mouse model is a feasible method aimed at identifying novel targets for the prevention of cartilage destruction in RA.


Sleep quality and polysomnographic changes in patients with chronic pain with and without central sensitization signs.
Insufficient sleep is common nowadays and it can be associated with chronic pain. To describe the main polysomnographic findings in patients with chronic musculoskeletal pain and to estimate the association between sleep quality, polysomnography variables and chronic musculoskeletal pain. This cross-sectional research analyzed a database from polysomnography type 1 exams results and then collected data via an electronic form from these patients. The form collected sociodemographic data and presented clinical questionnaires for measuring sleep quality, sleepiness, pain intensity and central sensitization signs. Pearson's correlation coefficient and odds ratio were used to estimate the associations. The mean age of the respondents was 55.1 (SD 13.4) years. The mean score of the Central Sensitization Inventory showed signs of central sensitization (50.1; SD 13.4) in the participants. Most patients (86%) had 1 or more nocturnal awakenings, 90% had one or more episodes of sleep apnea, 47% had Rapid Eye Movement sleep phase latency greater than 70-120 min and the mean sleep efficiency among all participants was 81.6%. The Pittsburgh Sleep Quality Index score was correlated with the CSI score (r = 0.55; 95% CI: 0.45, 0.61). People with central sensitization signs have 2.6 times more chance to present sleep episodes of blood oxygen saturation below 90% (OR = 2.62; 95% CI:1.23, 6.47). Most people with central sensitization signs had poor sleep quality, night waking episodes and specific disturbances in sleep phases. The findings showed association between central sensitization, sleep quality, nocturnal awakening, and changes in blood oxygen saturation during sleep.


Ungual squamous cell carcinoma mimicking a chronic paronychia: clinical, pathological and radiological correlation.
Squamous cell carcinoma is a malignant skin tumor that is rarely located in the nails. Its presentation, can sometimes be confused with an inflammatory process as onychomycosis or psoriatic onychopathy or other tumors as viral warts. We report the case of a 73-year-old woman with a locally invasive squamous cell carcinoma reaching the bone, simulating a chronic paronychia.


Dynamics of alternative polyadenylation in human preimplantation embryos.
Alternative polyadenylation (APA) affects the length of the 3' untranslated region (3'-UTR) and the regulation of microRNAs. Previous studies have shown that cancer cells tend to have shorter 3'-UTRs than normal cells. A plausible explanation for this is that it enables cancer cells to escape the regulation of microRNAs. Here, we extend this concept to an opposing context: changes in 3'-UTR length in the development of the human preimplantation embryo. Unlike cancer cells, during early development 3'-UTRs tended to become longer, and gene expression was negatively correlated with 3'-UTR length. Moreover, our functional enrichment results showed that length changes are part of the development mechanism. We also investigated the analogy of 3'-UTR length variation with respect to lncRNAs and found that, similarly, lncRNA length tended to increase during embryo development.


N-acetylcysteine normalizes glutamate levels in cocaine-dependent patients: a randomized crossover magnetic resonance spectroscopy study.
Treatment with N-acetylcysteine (NAC) normalizes glutamate (Glu) homeostasis and prevents relapse in drug-dependent animals. However, the effect of NAC on brain Glu levels in substance-dependent humans has not yet been investigated. Proton magnetic resonance spectroscopy ((1)H MRS) was used to investigate Glu changes in the dorsal anterior cingulate cortex (dACC) after a single dose of NAC in cocaine-dependent patients and normal controls. In an open-label, randomized, crossover study, 8 cocaine-dependent patients and 14 healthy controls underwent two scan sessions: one group receiving no compound and the other following a single administration of 2400 mg NAC. The Barratt Impulsiveness Scale was administered to examine the relation between dACC Glu levels and impulsivity. In the medication-free condition, Glu levels in the dACC were significantly higher in cocaine-dependent patients compared with healthy controls. After administration of NAC, Glu levels were reduced in the cocaine-dependent group, whereas NAC had no effect in healthy controls. Higher baseline Glu levels were associated with higher impulsivity, and both were predictive of greater NAC-induced Glu reduction. The current findings indicate that NAC can normalize elevated Glu levels in cocaine-dependent patients. These findings may have important implications for treatment, because abnormal Glu levels are related to relapse, and treatment with NAC prevented relapse in animal studies. Furthermore, clinical studies have indicated beneficial effects of NAC in cocaine-dependent patients, and the current study suggests that these beneficial effects might in part be mediated by the ability of NAC to normalize glutamatergic abnormalities.


The actin binding protein, fesselin, is a member of the synaptopodin family.
Fesselin is a natively unfolded protein that is abundant in avian smooth muscle. Like many natively unfolded proteins, fesselin has multiple binding partners including actin, myosin, calmodulin and alpha-actinin. Fesselin accelerates actin polymerization and bundles actin. These and other observations suggest that fesselin is a component of the cytoskeleton. We have now cloned fesselin and have determined the cDNA derived amino acid sequence. We verified parts of the sequence by Edman analysis and by mass spectroscopy. Our results confirmed fesselin is homologous to human synaptopodin 2 and belongs to the synaptopodin family of proteins.