Unvaccinated Children Are an Important Link in the Transmission of SARS-CoV-2 Delta Variant (B1.617.2): Comparative Clinical Evidence From a Recent Community Surge.
To evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China. A total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis. The Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10^9/L vs. 1.31 (0.94, 1.85)×10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28 (3.31, 8.13) vs. 9.10 (4.37, 15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13 (0.00, 0.09) vs. 0.12 (0.03, 0.41), p<0.05; 0.02 (0.00, 0.14) vs. 1.94 (0.54, 6.40), p<0.05; 5.46 (2.41, 9.26) vs. 73.63 (54.63, 86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13). Unvaccinated children may be an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2), which indicated an urgent need of vaccination for this particular population.


Polarization and migration in the zebrafish posterior lateral line system.
Collective cell migration plays an important role in development. Here, we study the posterior lateral line primordium (PLLP) a group of about 100 cells, destined to form sensory structures, that migrates from head to tail in the zebrafish embryo. We model mutually inhibitory FGF-Wnt signalling network in the PLLP and link tissue subdivision (Wnt receptor and FGF receptor activity domains) to receptor-ligand parameters. We then use a 3D cell-based simulation with realistic cell-cell adhesion, interaction forces, and chemotaxis. Our model is able to reproduce experimentally observed motility with leading cells migrating up a gradient of CXCL12a, and trailing (FGF receptor active) cells moving actively by chemotaxis towards FGF ligand secreted by the leading cells. The 3D simulation framework, combined with experiments, allows an investigation of the role of cell division, chemotaxis, adhesion, and other parameters on the shape and speed of the PLLP. The 3D model demonstrates reasonable behaviour of control as well as mutant phenotypes.


PROPOFOL AS AN IMMERSION ANESTHETIC AND IN A MINIMUM ANESTHETIC CONCENTRATION (MAC) REDUCTION MODEL IN GOLDFISH (CARASSIUS AURATUS).
Propofol is a novel immersion anesthetic in goldfish ( Carassius auratus ). Objectives were to characterize propofol as an anesthetic and assess its suitability in a minimum anesthetic concentration (MAC) reduction model. Using a crossover design, eight goldfish were submerged in 1, 5, or 10 mg/L propofol. Data included induction time, recovery time, heart rate, opercular rate, and response to supramaximal stimulation. Baseline MAC (Dixon's up-and-down method) was determined, and 15 fish were anesthetized with propofol on 4 consecutive days with MAC determination on the fifth day, weekly, for 1 mo. Using a crossover design, MAC of propofol (n = 15) was determined 1 hr following administration of i.m. butorphanol 0.05, 0.5, and 1 mg/kg, dexmedetomidine 0.01, 0.02, and 0.04 mg/kg, ketoprofen 0.5, 1, and 2 mg/kg, morphine 5, 10, and 15 mg/kg, or saline 1 ml/kg. Comparisons were performed with Wilcoxon signed-rank tests (P < 0.05) and Tango's score confidence interval. Propofol at 1 mg/L did not produce anesthesia. Induction time with 10 mg/L (112, 84-166 s) was faster than 5 mg/L (233, 150-289 s; P = 0.0078). Heart and opercular rates for 5 and 10 mg/L were 36 (24-72) beats/min, 58 (44-68) operculations/min and 39 (20-48) beats/min, 57 (48-80) operculations/min, respectively. Recovery time was 249 (143-396) s and 299 (117-886) s with 5 and 10 mg/L, respectively. Response to supramaximal stimulation was not significantly different with 5 mg/L (1/8) compared with 10 mg/L (0/8). Baseline and weekly MAC following daily exposure was 8.4 and 9.0, 8.1, 8.1, and 8.7 mg/L, respectively. MAC reduction was no more than 8% following any drug or dosage. Propofol at 5 and 10 mg/L produced anesthesia, and anesthetic needs were similar following repeated exposure. Propofol was not suitable to test MAC reduction in goldfish in this study.


Monitoring and analysis of the change process in curriculum mapping compared to the National Competency-based Learning Objective Catalogue for Undergraduate Medical Education (NKLM) at four medical faculties. Part I: Conducive resources and structures.
Objective: After passing of the National Competency-based Learning Objectives Catalogue in Medicine (Nationaler Kompetenzbasierter Lernzielkatalog Medizin, [NKLM, retrieved on 22.03.2016]), the German medical faculties must take inventory and develop their curricula. NKLM contents are expected to be present, but not linked well or sensibly enough in locally grown curricula. Learning and examination formats must be reviewed for appropriateness and coverage of the competences. The necessary curricular transparency is best achieved by systematic curriculum mapping, combined with effective change management. Mapping a complex existing curriculum and convincing a faculty that this will have benefits is not easy. Headed by Tübingen, the faculties of Freiburg, Heidelberg, Mannheim and Tübingen take inventory by mapping their curricula in comparison to the NKLM, using the dedicated web-based MERLIN-database. This two-part article analyses and summarises how NKLM curriculum mapping could be successful in spite of resistance at the faculties. The target is conveying the widest possible overview of beneficial framework conditions, strategies and results. Part I of the article shows the beneficial resources and structures required for implementation of curriculum mapping at the faculties. Part II describes key factors relevant for motivating faculties and teachers during the mapping process. Method: The network project was systematically planned in advance according to steps of project and change management, regularly reflected on and adjusted together in workshops and semi-annual project meetings. From the beginning of the project, a grounded-theory approach was used to systematically collect detailed information on structures, measures and developments at the faculties using various sources and methods, to continually analyse them and to draw a final conclusion (sources: surveys among the project participants with questionnaires, semi-structured group interviews and discussions, guideline-supported individual interviews, informal surveys, evaluation of target agreements and protocols, openly discernible local, regional or over-regional structure-relevant events). Results: The following resources and structures support implementation of curriculum mapping at a faculty: Setting up a coordination agency (≥50% of a full position; support by student assistants), systematic project management, and development of organisation and communication structures with integration of the dean of study and teaching and pilot departments, as well as development of a user-friendly web-based mapping instrument. Acceptance of the mapping was increased particularly by visualisation of the results and early insight into indicative results relevant for the department. Conclusion: Successful NKLM curriculum mapping requires trained staff for coordination, resilient communication structures and a user-oriented mapping database. In alignment with literature, recommendations can be derived to support other faculties that want to map their curriculum.


Probing the Role of the Bridging Nitrogen in the Signaling Mechanism of an Anthracene-Boronic Acid Sugar Sensor and a Different Version of the PET-Based Mechanism.
The N-quaternized derivative 5 of the James-Shinkai anthracene-boronic acid fluorescence sugar sensor 1 was prepared to probe the role of the bridging nitrogen in the signaling mechanism of 1. Both 5 and 1 contain positively charged bridging groups NMe+ or NH+, respectively, but 5 lacks the ability to form the intramolecular ammonium-boronate doubly ionic hydrogen bond present in 1. Receptors 1 and 5 display opposite fluorescence vs pH profiles with a small turn-on effect of the sugar binding to the zwitterion of 5 in contrast to a large effect observed with 1. It is concluded that the ammonium-boronate hydrogen bond is essential for the signaling mechanism of 1. Its possible function is enabling the PET quenching effect by shifting the NH+ proton toward boronate anion inside the hydrogen bond, the degree of which is modulated by the ester formation with diols affecting the basicity of boronate anion. This mechanism agrees with observed signaling selectivity of 1 toward a series of di- and polyols of variable structures as well as with the behavior of 1 in buffered D2O and methanol solvents at controlled pH and provides an addition to the established "loose bolt" mechanism signaling mode essential for receptors with nonpolar fluorophores.


The MS Center of Saint Louis: a practice perspective of the impacts of high cost sharing.
As treatment for multiple sclerosis (MS) has become increasingly expensive, patients have had to shoulder a greater cost-sharing burden. This case study follows a fictitious patient as she encounters the common cost-related barriers to treatment that have been observed by providers at the MS Center of Saint Louis. Medications, tests to monitor patient safety on medications, physical therapy, occupational therapy, medical equipment, mental health counseling, transportation, and modifications to house or vehicles are all common needs of MS patients that increase their cost burden. The MS Center of Saint Louis provides care management and education to help patients budget for expected expenses and navigate resources for assistance. However, this will ultimately be an unsustainable solution without substantial policy change.


Marfan syndrome: current perspectives.
Marfan syndrome (MFS) is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. The FBN1 gene, which is made of 66 exons, is located on chromosome 15q21.1. This review, after an introduction on the clinical manifestations that leads to the diagnosis of MFS, focuses on cardiovascular manifestations, pharmacological and surgical therapies of thoracic aortic aneurysm and/or dissection (TAAD), mechanisms underlying the progression of aneurysm or of acute dissection, and biomarkers associated with progression of TAADs. A Dutch group compared treatment with losartan, an angiotensin II receptor-1 blocker, vs no other additional treatment (COMPARE clinical trial). They observed that losartan reduces the aortic dilatation rate in patients with Marfan syndrome. Later on, they also reported that losartan exerts a beneficial effect on patients with Marfan syndrome carrying an FBN1 mutation that causes haploinsufficiency (quantitative mutation), while it has no significant effect on patients displaying dominant negative (qualitative) mutations. Moreover, a French group in a 3-year trial compared the administration of losartan vs placebo in patients with Marfan syndrome under treatment with beta-receptor blockers. They observed that losartan decreases blood pressure but has no effect on aortic diameter progression. Thus, beta-receptor blockers remain the gold standard therapy in patients with Marfan syndrome. Three potential biochemical markers are mentioned in this review: total homocysteine, serum transforming growth factor beta, and lysyl oxidase. Moreover, markers of oxidative stress measured in plasma, previously correlated with clinical features of Marfan syndrome, may be explored as potential biomarkers of clinical severity.


Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal.
Rheumatic heart disease (RHD) remains a major contributor to morbidity and mortality in developing countries. The reported prevalence rates of RHD are highly variable and mainly attributable to differences in the sensitivity of either clinical screening to detect advanced heart disease or echocardiographic evaluation where disease is diagnosed earlier across a continuous spectrum. The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established. The authors designed a cross-sectional survey to determine the prevalence of RHD in children from private and public schools between the age of 5 and 15 years in urban and rural areas of Eastern Nepal using both cardiac auscultation and echocardiographic evaluation. Children with RHD will be treated with secondary prevention and enrolled in a prospective cohort study. The authors will compare the prevalence rates by cardiac auscultation and echocardiography, determine risk factors associated with diagnosis and progression of RHD, investigate social and economic barriers for receiving adequate cardiac care and assess clinical outcomes with regular medical surveillance as a function of stage of disease at the time of diagnosis. Prospective clinical studies investigating the impact of secondary prevention for subclinical RHD on long-term clinical outcome will be of central relevance for future health resource utilisation in developing countries. The study was considered ethically uncritical and was given an exempt status by the ethics committee at University of Bern, Switzerland. The study has been submitted to the National Nepal Health Research Council and was registered with http://www.ClinicalTrials.gov (NCT01550068). The study findings will be reported in peer-reviewed publications. CLINICALTRIALS.GOV IDENTIFIER: NCT01550068.


Arteriovenous malformations within jejunal diverticulosis: case report and literature review.
Jejunal diverticula are the rarest of all small bowel diverticula. Most patients with jejunal diverticula are asymptomatic. Major complications include diverticulitis, gastrointestinal hemorrhage, intestinal obstruction and perforation. The hemorrhage has been attributed to diverticulitis with ulceration, diverticulosis associated with trauma and irritation disorder. However, only six cases reported the arteriovenous malformations within jejunal diverticulosis to be the cause of hemorrhage. We present a case of arteriovenous malformations within jejunal diverticulosis in a 68-year-old male presented with lower gastrointestinal bleeding. After admission and stabilization, upper and lower endoscopies were performed without demonstrating the bleeding site. They only revealed clotted and red blood throughout the colon. Technetium-labeled red blood cell bleeding scan, endoscopic capsule, and selective angiography were performed to localize the site of bleeding without significant findings. As the clinical status of the patient deteriorated, exploratory laparotomy was performed urgently. Extensive jejunal saccular pouches were found 10 cm distal to duodenojejunal junction extending 1.6 m distally. Segmental resection was performed with side to side primary anastomosis. Microscopic examination of the specimen revealed many diverticula. He was followed up 2 years after that without complications. We report yet the seventh case jejunal diverticulosis with the presence of angiodysplasia, in hope of expanding the knowledge of a rare occurrence and increasing the demand for further research about the etiology, clinical impact and treatment of such anomalies coexistence. This case also highlights the importance of considering the diagnosis of AVMs within jejunal diverticulosis in the presence of uncontrollable blood loss in the pre- or intra- operatively diagnosed jejunal diverticulosis and the urgent need for surgical intervention. In addition, the diagnostic tests should be performed close to the bleeding episode.


Factors Influencing the Willingness of Allied Health Students to Donate Organs or Tissues.
There has been an increase in the number of patients waiting for organ transplantation. A questionnaire on knowledge and attitude toward organ donation was completed by 434 allied health students. Overall knowledge about the various aspects of organ donation was adequate and was higher among women and clinical students. Although the majority were willing to be living donors for their families, very few students supported deceased organ donation, and even fewer of them had thought about an organ donation card. Despite the good knowledge, an overall positive attitude toward deceased donation was held by only 44% of the students. In contrast, the attitude toward directed living organ donation to family members was favorable in 83.1% of the respondents, which seems to be influenced by cultural and sociodemographic factors. Our findings indicate that the most frequent cause of refusal to donate organs among students with negative attitudes was the mistrust of medical staff regarding brain death diagnosis (49.9%), followed by bodily concerns (18.1%) and religion (9.9%). Quite a few of our respondents supported commercial donation, which was attributed to the less knowledgeable groups. Respondents who were willing to donate organs indicated that the reason was for helping others and sympathy. This study identified that the main source of information about organ donation for the respondents was television, followed by relatives/friends and the internet. The misconception of the students toward deceased donation needs to be improved by integrating the concepts of brain death within the curriculum of allied health students.


Restrictiveness of care among the severely mentally disabled.
Restrictiveness of care was assessed among 286 severely mentally disabled individuals known to an urban community mental health center. By examining clinical records, the authors rated each subject for each month during a period of up to 85 months on four dimensions of restrictiveness: physical freedom, time constraints, legal status, and conservatorship. The maximum restrictiveness experienced by most of the subjects was high, reflecting periodic involuntary hospitalization. The average restrictiveness they experienced, however, was well below the level represented by state hospital care. Thus the authors suggest that the average restrictiveness experienced by this population has been reduced since the initiation of deinstitutionalization.


The use of caries detector dye in diagnosis of occlusal carious lesions.
The purpose of this in vitro study was to compare the accuracy of diagnosis of carious lesions in the occlusal pit, fissure, and groove system of lower molars examined by two methods: examination by using caries detector dye. vs. traditional tactile examination using a dental explorer. Thirty human lower permanent molars were examined in this study. The occlusal surface of each tooth was examined by explorer; a linear measurement in millimeters of carious lesions diagnosed in the pit, fissure and groove system was recorded. The same surface was then stained with caries detection dye. Linear measurements in millimeters were then recorded for areas of stain remaining in the pit, fissure, and groove system. The thirty teeth were then sectioned buccal lingually in three sections, exposing 180 saggital histological cross sections for histological examination. Histological cross section confirmed a ratio of 1:1 (100%) accuracy by caries detection dye in diagnosing decay underlying the occlusal surface. Concurrent examination of the same occlusal surfaces by traditional explorer examination was reliable only in a 1:4 ratio (25%). Other findings of significance revealed by histological examination of the cross sections include: a sub-ridge occlusal transverse ridge of enamel; different shape and direction of occlusal grooves compared to traditional teaching; and unpredictable path of caries underlying the occlusal grooves.


(-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma.
We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment.


Prioritizing environmental issues around the world: opinions from an international Central and Eastern European environmental health conference.
As the next generation of scientists enters the field of environmental health, it is imperative that they view their contributions in the context of global environmental stewardship. In this commentary, a group of international graduate students facilitated by three experienced environmental health scientists present their views on what they consider to be the global environmental health concerns of today. This group convened initially in October 2004 at an international health conference in Prague, Czech Republic. In this report we identify perceived environmental health concerns that exist around the world, with a focus on Central and Eastern Europe. Additionally, we address these perceived problems and offers some potential solutions. At the meeting, students were invited to participate in two panel discussions. One group of young international scientists identified several significant global environmental health concerns, including air pollution, occupational hazards, and risk factors that may exacerbate current environmental health issues. The second panel determined that communication, education, and regulation were the mechanisms for addressing current environmental challenges. In this commentary we expand on the views presented at the meeting and represent the concerns of young investigators from nine different countries. We provide ideas about and support the exchange of information between developed and developing countries on how to handle the environmental health challenges that face the world today.


The PI3K/Akt and ERK pathways elevate thyroid hormone receptor β1 and TRH receptor to decrease thyroid hormones after exposure to PCB153 and p,p'-DDE.
PCBs and DDT cause the disturbance of thyroid hormone (TH) homeostasis in humans and animals. To test the hypothesis that the PI3K/Akt and MAPK pathways would play significant roles in TH imbalance caused by PCBs and DDT, Sprague-Dawley rats were dosed with PCB153 and p,p'-DDE intraperitoneally for 5 consecutive days, and human thyroid follicular epithelial (Nthy-ori 3-1 cell line) were treated with PCB153 and p,p'-DDE for different time. Results showed that serum total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3) and thyroid stimulating hormone (TSH) were decreased, whereas serum free triiodothyronine (FT3) and thyrotropin releasing hormone (TRH) were not changed. The PI3K/Akt and ERK pathways were activated in vivo and in vitro after the treatment with PCB153 and p,p'-DDE. Moreover, TH receptor β1 (TRβ1) was elevated after the activation of the PI3K/Akt pathway and was depressed after the inhibition of the PI3K/Akt pathway; TRH receptor (TRHr) was increased after the activation of the ERK pathway and was decreased after the inhibition of the ERK pathway. Though TH receptor α1 (TRα1) level was increased in the hypothalamus, TRα1 and TSHr were not influenced by the status of signaling pathways in in vitro study. Taken together, after exposure to PCB153 and p,p'-DDE, activated PI3K/Akt and ERK pathways disrupt the hypothalamic-pituitary-thyroid (HPT) axis via TRβ1 and TRHr and then decrease TH levels, and that would be a potential mechanism by which PCBs and DDT disturb TH homeostasis.


Autism and maternally derived aberrations of chromosome 15q.
Of the chronic mental disabilities of childhood, autism is causally least well understood. The former view that autism was rooted in exposure to humorless and perfectionistic parenting has given way to the notion that genetic influences are dominant underlying factors. Still, identification of specific heritable factors has been slow with causes identified in only a few cases in unselected series. A broad search for genetic and environmental influences that cause or predispose to autism is the major thrust of the South Carolina Autism Project. Among the first 100 cases enrolled in the project, abnormalities of chromosome 15 have emerged as the single most common cause. The four abnormalities identified include deletions and duplications of proximal 15q. Other chromosome aberrations seen in single cases include a balanced 13;16 translocation, a pericentric inversion 12, a deletion of 20p, and a ring 7. Candidate genes involved in the 15q region affected by duplication and deletion include the ubiquitin-protein ligase (UBE3A) gene responsible for Angelman syndrome and genes for three GABA(A) receptor subunits. In all cases, the deletions or duplications occurred on the chromosome inherited from the mother.


Views on teaching-learning: lessons learned from nursing education in Sweden.
Although change sometimes feels risky, nurse educators continually search for more effective ways of teaching. Different approaches to teaching-learning were experienced during a visiting professorship at a Swedish university. Ethnographic methods involving participant observation and interviews with faculty and students were used to understand the educational philosophy and methods of teaching and learning. Reflection exercises and suggestions provide ideas about how these approaches might be adapted for use in the United States.


CArbon dioxide surgical field flooding and aortic NO-touch off-pump coronary artery bypass grafting to reduce Neurological injuries after surgical coronary revascularisation (CANON): protocol for a randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms.
Neurological injuries remain a major concern following coronary artery bypass grafting (CABG) that offsets survival benefit of CABG over percutaneous coronary interventions. Among numerous efforts to combat this issue is the development of off-pump CABG (OPCABG) that obviates the need for extracorporeal circulation and is associated with improved neurological outcomes. The objective of this study is to examine whether the neuroprotective effect of OPCABG can be further pronounced by the use of two state-of-the-art operating techniques. In this randomised, controlled, investigator and patient blinded single-centre superiority trial with three parallel arms, a total of 360 patients will be recruited. They will be allocated in a 1:1:1 ratio to two treatment arms and one control arm. Treatment arms undergoing either aortic no-touch OPCABG or OPCABG with partial clamp applying carbon dioxide surgical field flooding will be compared against control arm undergoing OPCABG with partial clamp. The primary endpoint will be the appearance of new lesions on control brain MRI 3 days after surgery. Secondary endpoints will include the prevalence of new focal neurological deficits in the first 7 days after surgery, the occurrence of postoperative cognitive dysfunction at either 1 week or 3 months after surgery and the incidence of delirium in the first 7 days after surgery. Data will be analysed on intention-to-treat principles and a per protocol basis. Ethical approval has been granted for this study. Results will be disseminated through peer-reviewed media. NCT03074604; Pre-results. 10-Mar-2017 Original.


Orbital fat prolapse and dermolipoma: two distinct entities.
A subconjunctival orbital fat prolapse is frequently confused with a dermolipoma clinically. These two entities have similar clinical appearances, but are clearly distinct. The clinical features, differential diagnosis, and treatment modalities of subconjunctival orbital fat prolapse and dermolipoma are discussed.


(Per)chlorate in Biology on Earth and Beyond.
Respiration of perchlorate and chlorate [collectively, (per)chlorate] was only recognized in the last 20 years, yet substantial advances have been made in our understanding of the underlying metabolisms. Although it was once considered solely anthropogenic, pervasive natural sources, both terrestrial and extraterrestrial, indicate an ancient (per)chlorate presence across our solar system. These discoveries stimulated interest in (per)chlorate microbiology, and the application of advanced approaches highlights exciting new facets. Forward and reverse genetics revealed new information regarding underlying molecular biology and associated regulatory mechanisms. Structural and functional analysis characterized core enzymes and identified novel reaction sequences. Comparative genomics elucidated evolutionary aspects, and stress analysis identified novel response mechanisms to reactive chlorine species. Finally, systems biology identified unique metabolic versatility and novel mechanisms of (per)chlorate respiration, including symbiosis and a hybrid enzymatic-abiotic metabolism. While many published studies focus on (per)chlorate and their basic metabolism, this review highlights seminal advances made over the last decade and identifies new directions and potential novel applications.


[Tumour-induced precocious puberty. Discussion of the indications for neurosurgery (author's transl)].
The tumour aetiology of precocious puberty is sometimes clinically evident when accompanied by visual disturbances or by raised intracranial pressure. It may be suspected in the presence of accelerated puberty but should also be feared in cases of apparently idiopathic precocious puberty. In the 13 cases studied, the tumour was studied in the posterior hypothalamus. Ten children underwent surgery (with additional radiotherapy in two cases). Two children died, the follow-up varying at present between 2 and 12 years. Amongst the various tumours, the hamartoma has a special nature by virtue of slow or absence of increase in tumour size. When the clinical and radiological signs suggest this type of tumour, abstention from surgery with close observation of the size of the tumour and medical slowing of puberty is advised.


Sphingosine-1-phosphate induces islet β-cell proliferation and decreases cell apoptosis in high-fat diet/streptozotocin diabetic mice.
Sphingosine-1-phosphate (S1P) has been reported to enhance the function of islet β-cells, providing a potential therapeutic target for diabetes mellitus. In the present study, the effects of S1P on the proliferation and apoptosis of β-cells in type 2 diabetic mice were investigated. The mice were administered intraperitoneal S1P solution daily at a dose of 20 µg/kg for three weeks. The intraperitoneal glucose tolerance test (IPGTT) and homeostatic model assessment of insulin resistance (HOMA-IR) index determination were carried out. Immunohistochemical staining was used to detect the protein expression of insulin, antigen Ki-67 and S1P receptor isoforms (S1PR1/S1PR2/S1PR3) in pancreatic islets. Compared with the diabetic control (DC) group, the IPGTT results and HOMA-IR index in the S1P treatment group were decreased. The islets in the S1P group exhibited higher insulin immunostaining intensity than the DC group, as well as higher proliferation (P<0.05) and lower apoptosis rates (P<0.05). Positive staining for the S1P receptors S1PR1, S1PR2 and S1PR3 was observed in the cytoplasm and membrane of the islet cells. S1PR1 and S1PR2 proteins showed increased expression in the S1P and DC groups compared with the normal control group (P<0.01 and P<0.05, respectively), whereas no significant difference was observed in the expression of S1PR3 among these groups. In conclusion, extracellular S1P can induce islet β-cell proliferation and decrease cell apoptosis in diabetic mice. S1P function may be mediated via S1PR1 and S1PR2; therefore, targeting S1P/S1PR signalling pathways may be a novel therapeutic strategy for diabetes mellitus.


Sinus histiocytosis with massive lymphadenopathy and subglottic stenosis: a case report.
An 18 year-old woman presented with massive cervical lymphadenopathy. She also had bilateral parotid gland enlargement, and later upper airway obstruction from subglottic mass compression. Surgical excision of lymph nodes and bilateral total parotidectomy with facial nerve preservation were selected. Direct laryngoscopy and CO2 laser excision were used to remove the subglottic mass. Airway was secured by tracheostomy and after that it was removed. Histologic finding was Sinus histiocytosis with massive lymphadenopathy (SHML) that involved the subglottic. SHML is very rare, probably less than 1000 cases reported in the literature and this is the 6th case in the literature that involved the subglottic. There are no standard treatment modalities. The treatment is comprised of surgery, steroid, chemotherapy and local control. In the present case the authors chose surgery, steroid and local control of disease in the subglottic by using CO2 laser excision. Now, the disease is under control.


SUMOylation: Novel Neuroprotective Approach for Alzheimer's Disease?
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized in the brain by the formation of amyloid-beta (Aβ)-containing plaques and neurofibrillary tangles containing the microtubule-associated protein tau. Neuroinflammation is another feature of AD and astrocytes are receiving increasing attention as key contributors. Although some progress has been made, the molecular mechanisms underlying the pathophysiology of AD remain unclear. Interestingly, some of the main proteins involved in AD, including amyloid precursor protein (APP) and tau, have recently been shown to be SUMOylated. The post-translational modification by SUMO (small ubiquitin-like modifier) has been shown to regulate APP and tau and may modulate other proteins implicated in AD. Here we present an overview of recent studies suggesting that protein SUMOylation might be involved in the underlying pathogenic mechanisms of AD and discuss how this could be exploited for therapeutic intervention.


Optimized cardiac magnetic resonance imaging inversion recovery sequence for metal artifact reduction and accurate myocardial scar assessment in patients with cardiac implantable electronic devices.
Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is the gold standard for imaging myocardial viability. An important application of LGE CMR is the assessment of the location and extent of the myocardial scar in patients with ventricular tachycardia (VT), which allows for more accurate identification of the ablation targets. However, a large percentage of patients with VT have cardiac implantable electronic devices (CIEDs), which is a relative contraindication for cardiac magnetic resonance imaging due to safety and image artifact concerns. Previous studies showed that these patients can be safely scanned on 1.5 T scanners provided that an adequate imaging protocol is adopted. Nevertheless, imaging patients with a CIED result in metal artifacts due to the strong frequency off-resonance effects near the device; therefore, the spins in the surrounding myocardium are not completely inverted, and thus give rise to hyperintensity artifacts. These artifacts obscure the myocardial scar tissue and limit the ability to study the correlation between the myocardial scar structure and the electro-anatomical map during catheter ablation. In this study, we developed a modified inversion recovery technique to alleviate the CIED-induced metal artifacts and improve the diagnostic image quality of LGE images in patients with CIEDs without increasing scan time or requiring additional hardware. The developed technique was tested in phantom experiments and in vivo scans, which showed its capability for suppressing the hyperintensity artifacts without compromising myocardium nulling in the resulting LGE images.


Ultrasonographic and computed tomographic features of a true gastro-gastric intussusception with concurrent foreign bodies in a dog.
A 2-year-old intact male Cane Corso dog was presented for acute weakness, vomiting, and diarrhea. Abdominal ultrasound revealed the stomach had severe wall edema and a target appearance. Computed tomography was consistent with a gastro-gastric intussusception and concurrent mineral-like gastric foreign bodies. After reduction of the intussusception, bilateral incisional gastropexy was performed to prevent recurrence. True gastrogastric intussusception is a rare condition and should be considered if the stomach has severe wall edema with a target sign on abdominal ultrasound. Computed tomography was useful to confirm this rare diagnosis and screen the entire abdomen for concurrent lesions. Key clinical message: This case highlights the usefulness of a CT examination to confirm this rare diagnosis, to determine the position of gastric compartments, and to detect potential concurrent lesions prior to surgery.


Humerus Lengthening: A Comparison of the Internal Lengthening Nail to External Fixation.
Introduction: Magnetic internal lengthening nails (MILNs) have been used for humeral lengthening to avoid complications associated with external fixation. Purpose/Questions: We compared the 1-year Disabilities of the Arm, Shoulder and Hand (DASH) score, adjacent joint range of motion (ROM), bone healing index (BHI), length achieved, distraction rate, and complications when lengthening the humerus using MILN vs using external fixation. Methods: We conducted a retrospective cohort study of 18 patients (22 humeri) from January 2001 to March 2020 divided into 2 groups, the MILN group (7 patients, 7 humeri) and the mono-lateral fixator group (11 patients, 15 humeri). Results: The MILN group showed larger improvement of DASH scores (average 26.8 and 8 for MILN and fixator groups, respectively), less loss of elbow ROM (average 5° and 7° for MILN and fixator groups, respectively), and shorter time to full recovery of elbow ROM (average 39 days and 122 days for MILN and fixator groups, respectively). In the MILN group, there was slower distraction rate (average 0.66 mm/day and 0.86 mm/day for MILN and fixator groups, respectively), less lengthening achieved (average 5.2 cm and 7 cm for MILN and fixator group, respectively), and a lower lengthening percentage (average 19% and 41% for MILN and fixator group, respectively). Bone healing index (BHI) of 0.94 and 0.99 months/cm for the MILN and the fixator groups were similar. Conclusion: Humeral lengthening using the MILN allowed for early full recovery of joint ROM with comparable functional and radiographic outcomes compared with using external fixators.


[Therapeutic treatment with neuroleptics. II: Subjective mechanisms of effect, compliance and consequences for treatment strategy].
The problems of subjective acceptance and reaction by the patients to the effects produced by neuroleptics, have been receiving far more less attention so far than the "objective" aspects, and have not yet been empirically tested to the same extent. However, papers have been published recently in connection with this complex within the framework of researches into concept of disease and into compliance. These papers supply proof of the tremendous significance of the patient's attitude to, and assessment of, pharmacotherapeutic measures. The following aspects are pointed out to be particularly important: The attitude and relation of the patient to his psychosis; the style of coping in the sense of integration or disintegration of the psychosis into the process of life; the dysphoric reactions to neuroleptics; and the disease pattern or disease model. Practical model examples are given to illustrate three possibilities of a more intensive connection between neuroleptic therapy and other therapeutic measures.


The effect of an H1 blocker, chlorpheniramine maleate, on total menstrual loss.
50 subjects participated in a 4-month study of the effects of an antihistamine on total menstrual loss. During the first 2 periods, no drugs were given; during the last 2 periods, an antihistamine or a placebo was administered according to a double-blind format. The menstrual weights of the first 2 months were averaged and compared with averages from the last 2 months combined. The treated group showed an average decrease in menstrual loss of 11.30 g compared to a decrease of 0.98 g in the placebo group. While the difference in means was not statistically significant, the variance between the 2 groups was significant (p = 0.0002), indicating that the antihistamine, chlorpheniramine maleate, was effective in reducing menstrual loss in certain individuals, but that the effect was neither uniform nor universal.


Validation of an analytical method based on the high-resolution continuum source flame atomic absorption spectrometry for the fast-sequential determination of several hazardous/priority hazardous metals in soil.
The aim of this paper was the validation of a new analytical method based on the high-resolution continuum source flame atomic absorption spectrometry for the fast-sequential determination of several hazardous/priority hazardous metals (Ag, Cd, Co, Cr, Cu, Ni, Pb and Zn) in soil after microwave assisted digestion in aqua regia. Determinations were performed on the ContrAA 300 (Analytik Jena) air-acetylene flame spectrometer equipped with xenon short-arc lamp as a continuum radiation source for all elements, double monochromator consisting of a prism pre-monocromator and an echelle grating monochromator, and charge coupled device as detector. For validation a method-performance study was conducted involving the establishment of the analytical performance of the new method (limits of detection and quantification, precision and accuracy). Moreover, the Bland and Altman statistical method was used in analyzing the agreement between the proposed assay and inductively coupled plasma optical emission spectrometry as standardized method for the multielemental determination in soil. The limits of detection in soil sample (3σ criterion) in the high-resolution continuum source flame atomic absorption spectrometry method were (mg/kg): 0.18 (Ag), 0.14 (Cd), 0.36 (Co), 0.25 (Cr), 0.09 (Cu), 1.0 (Ni), 1.4 (Pb) and 0.18 (Zn), close to those in inductively coupled plasma optical emission spectrometry: 0.12 (Ag), 0.05 (Cd), 0.15 (Co), 1.4 (Cr), 0.15 (Cu), 2.5 (Ni), 2.5 (Pb) and 0.04 (Zn). Accuracy was checked by analyzing 4 certified reference materials and a good agreement for 95% confidence interval was found in both methods, with recoveries in the range of 94-106% in atomic absorption and 97-103% in optical emission. Repeatability found by analyzing real soil samples was in the range 1.6-5.2% in atomic absorption, similar with that of 1.9-6.1% in optical emission spectrometry. The Bland and Altman method showed no statistical significant difference between the two spectrometric methods for 95% confidence interval. High-resolution continuum source flame atomic absorption spectrometry can be successfully used for the rapid, multielemental determination of hazardous/priority hazardous metals in soil with similar analytical performances to those in inductively coupled plasma optical emission spectrometry.


Sensitivity of polarization fluctuations to the nature of protein-water interactions: study of biological water in four different protein-water systems.
Since the time of Kirkwood, observed deviations in magnitude of the dielectric constant of aqueous protein solution from that of neat water (∼80) and slower decay of polarization have been subjects of enormous interest, controversy, and debate. Most of the common proteins have large permanent dipole moments (often more than 100 D) that can influence structure and dynamics of even distant water molecules, thereby affecting collective polarization fluctuation of the solution, which in turn can significantly alter solution's dielectric constant. Therefore, distance dependence of polarization fluctuation can provide important insight into the nature of biological water. We explore these aspects by studying aqueous solutions of four different proteins of different characteristics and varying sizes, chicken villin headpiece subdomain (HP-36), immunoglobulin binding domain protein G (GB1), hen-egg white lysozyme (LYS), and Myoglobin (MYO). We simulate fairly large systems consisting of single protein molecule and 20000-30000 water molecules (varied according to the protein size), providing a concentration in the range of ∼2-3 mM. We find that the calculated dielectric constant of the system shows a noticeable increment in all the cases compared to that of neat water. Total dipole moment auto time correlation function of water ⟨δMW(0)δMW(t)⟩ is found to be sensitive to the nature of the protein. Surprisingly, dipole moment of the protein and total dipole moment of the water molecules are found to be only weakly coupled. Shellwise decomposition of water molecules around protein reveals higher density of first layer compared to the succeeding ones. We also calculate heuristic effective dielectric constant of successive layers and find that the layer adjacent to protein has much lower value (∼50). However, progressive layers exhibit successive increment of dielectric constant, finally reaching a value close to that of bulk 4-5 layers away. We also calculate shellwise orientational correlation function and tetrahedral order parameter to understand the local dynamics and structural re-arrangement of water. Theoretical analysis providing simple method for calculation of shellwise local dielectric constant and implication of these findings are elaborately discussed in the present work.


"Neonatal Sepsis": Bacteria & their Susceptibility Pattern towards Antibiotics in Neonatal Intensive Care Unit.
Neonatal sepsis is one of the most common causes of neonatal mortality and morbidity, particularly in the developing countries. Its causative bacteria and their respective sensitivity patterns are different in each hospital and region. The objective of this study was to determine the causative bacteria and pattern of susceptibility to antibiotics in NICU of a tertiary care centre, which in turn may help in implementation of empirical therapy. This prospective study was carried out at a medical college during the period from 1st April 2011 to 31st March 2013. A total of 364 cases of suspected sepsis were admitted in our NICU during the mentioned period. Out of which, 137 cases were positive for culture. All the neonates of suspected sepsis were screened by using a panel consisting of CRP, ANC, I/T ratio, micro ESR and culture and sensitivity. A total of 137 cultures were found to be positive out of 364 cases. The most common organism isolated was Staphylococcus aureus (37.22%) followed by Klebsiella pneumoniae (27.01%) and Escherichia coli (19.70%). Other organisms were much less in number, which included pathogenic Streptococci, Coagulase negative Staphylococci (CoNS), Pseudomonas, Acinetobacter and Enterobacter species. The gram positive organisms except Streptococci displayed a high degree of resistance to most penicillins and ciprofloxacin but were sensitive to vancomycin, amikacin and cefepime. There was a high incidence of resistance noted with ampicillin, gentamicin and ciprofloxacin amongst most gram negative organisms' where-in cefepime, amikacin and meropenem were effective in most cases. There is an increasing trend of antibiotic resistance to the commonly used first line drugs. Continuous surveillance for antibiotic susceptibility is needed to ensure proper empirical therapy.


Lymph drainage from the upper and middle third of the rectum as demonstrated by 198 Au.
Extensive lymph node dissections have been performed in an attempt to increase survival after abdomino-perineal excision or anterior resection of the rectum for carcinoma. The lymph drainage from the upper and middle third of the rectum was demonstrated by means of 198Au which was injected into the submucosa. Less than one percent was drained to pelvic lymph nodes, giving little support for pelvic lymph node dissection for carcinoma in the upper and middle third of the rectum.


Fibrinogen adsorption on mica studied by AFM and in situ streaming potential measurements.
Adsorption of fibrinogen from aqueous solutions on mica was studied using AFM and in situ streaming potential measurements. In the first stage, bulk physicochemical properties of fibrinogen and the mica substrate were characterized for various ionic strength and pH. The zeta potential and number of uncompensated (electrokinetic) charges on the protein surfaces were determined from microelectrophoretic measurements. Analogously, using streaming potential measurements, the electrokinetic charge density of mica was determined for pH range 3-10 and the NaCl background electrolyte concentration of 10(-3) and 10(-2) M. Next, the kinetics of fibrinogen adsorption at pH 3.5 and 7.4 in the diffusion cell was studied using a direct AFM determination of the number of molecules per unit area of the mica substrate. Then, streaming potential measurements were performed to determine the apparent zeta potential of fibrinogen-covered mica for different pH and ionic strength in terms of its surface concentration. A quantitative interpretation of these streaming potential measurements was achieved in terms of the theoretical model postulating a side-on adsorption of fibrinogen molecules as discrete particles. On the basis of these results, the maximum coverage of fibrinogen Θ close to 0.29 was predicted, in accordance with previous theoretical predictions. It was also suggested that anomalous adsorption for pH 7.4, where fibrinogen and the mica substrate were both negatively charged, can be explained in terms of a heterogeneous charge distribution on fibrinogen molecules. It was estimated that the positive charge was 12 e (for NaCl concentration of 10(-2) M and pH 7.4) compared with the net charge of fibrinogen at this pH, equal to -21 e. Results obtained in this work proved that the coverage of fibrinogen can be quantitatively determined using the streaming potential method, especially for Θ < 0.2, where other experimental methods become less accurate.


Probiotic and prebiotic supplementation ameliorates chronic restraint stress-induced male reproductive dysfunction.
Restraint stress (RS) can induce male reproductive deficits by activating the hypothalamic-pituitary-adrenal (HPA) axis and causing oxidative stress. Previous studies have shown that probiotics can alleviate neurological and metabolic disorders induced by stress. However, the effects of probiotics on RS-induced reproductive deficits have not been fully elucidated. This study aimed to investigate whether Lactobacillus rhamnosus NCDC-610 (Probiotic-1) and Lactobacillus fermentum NCDC-400 (Probiotic-2) with prebiotic (fructooligosaccharides (FOS)) could prevent RS-induced reproductive deficits. C57BL6/J mice were subjected to RS for four hours daily before oral administration of probiotics (4 × 109 CFU per mice) either separately or concurrently with FOS. The results showed that oral administration of Probiotic-1 and Probiotic-2 protected against RS-induced sperm deficits, including sperm count, motility, morphology, and histopathology of testes, and improved intestinal health. Furthermore, Probiotic-1 and Probiotic-2 prevented RS-induced changes in testosterone levels by up-regulating the expressions of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme (P450scc), and 17β-hydroxysteroid dehydrogenase (17βHSD) in the testes. Additionally, Probiotic-1 and Probiotic-2 increased the activities of catalase and superoxide dismutase and reduced the fold change of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α), indicating a protective effect against RS-induced oxidative stress. Oral administration of Probiotic-1 and Probiotic-2, either separately or concurrently with FOS (probiotic dose of 4 × 109 CFU per mice and prebiotic 5% w/v), prevented RS-induced activation of the HPA axis and improved male fertility. These findings suggest that L. rhamnosus NCDC-610 and L. fermentum NCDC-400 are safe and effective probiotics for mitigating stress-induced male reproductive deficits.


Major themes for 2011 in cardiovascular anesthesia and intensive care.
The past year has witnessed major advances in of cardiovascular anesthesia and intensive care. Perioperative interventions such as anesthetic design, inotrope choice, glycemic therapy, blood management, and noninvasive ventilation have significant potential to enhance perioperative outcomes even further.The major theme for 2011 is the international consensus conference that focused on ancillary interventions likely to reduce mortality in cardiac anesthesia and intensive care. This landmark conference prioritized volatile anesthetics, levosimendan, and insulin therapy for their promising life-saving perioperative potential. Although extensive evidence has demonstrated the cardioprotective effects of volatile anesthetics, levosimendan as well as glucose, insulin and potassium therapy, the clinical relevance of these beneficial effects remains to be fully elucidated. Furthermore, controversy still persists about how tight perioperative glucose control should be in adult cardiac surgery because of the risk of hypoglycemia.A second major theme in 2011 has been perioperative hemostasis with the release of multispecialty guidelines. Furthermore, hemostatic agents such as recombinant factor VIIa and tranexamic acid have been studied intensively, even in the setting of major non-cardiac surgery. This review then highlights the remaining two major themes for 2011, namely the expanding role of noninvasive ventilation in our specialty and the formation of the Roland Hetzer International Cardiothoracic and Vascular Surgery Society.In conclusion, it is time for large adequately powered multicenter trials to test whether prioritized perioperative interventions truly reduce mortality and morbidity in cardiac surgical patients. This essential paradigm shift represents a major clinical opportunity for the global cardiovascular anesthesia and critical care community.


Household dietary diversity, vitamin A consumption and food security in rural Tigray, Ethiopia.
To describe: household dietary diversity across four zones in Ethiopia; the relationship between household dietary diversity and consumption of vitamin A-rich foods; and the relationship between household dietary diversity and food security status. This was a cross-sectional survey. Data were collected using structured questionnaires in the local language. Household dietary diversity scores measured types of foods households consumed, and households were classified by food security status using a modified version of the Household Food Insecurity Access Scale. An ordinal logistics regression model was created to assess the relationship between three tiers of dietary diversity (low, medium and high) and food security while controlling for agricultural zone, educational variables and household characteristics. Rural households in Tigray, Ethiopia. Three hundred households in Tigray, Ethiopia, were interviewed. Of the households, 23, 47 and 30 % had low, medium and high dietary diversity, respectively. Among households with high dietary diversity, eggs and fruit were the most common foods added to the diet. In the fully adjusted model, participants who reported being food secure had 1·8 increased odds of greater dietary diversity (95 % CI 1·0, 3·2) compared with participants who were food insecure. Food security was positively associated with dietary diversity. In order to enhance health, interventions that improve dietary diversity and vitamin A consumption should remain important areas of focus for health leaders in the region.


[Obesity in children: value of clinical evaluation criteria].
To clarify risk factors for obesity in children and look for factors affecting prognosis, simple clinical parameters were analyzed in 113 obese children at the first visit and during treatment. Height and weight charts were constructed. The main risk factors were parental obesity, excess weight at the age of one and above all young age at the time of the rebound in body mass index (W/H2). Severity of obesity was unrelated to spontaneous caloric intake but was negatively correlated with age at the time of rebound in body mass index (r = -0.34; p = 0.017) and above all with age at onset of obesity (r = -0.53; p < 0.001). Closely spaced measurements of weight, stature, and body mass index in high risk children would allow appropriate preventive treatment before the phase of established obesity. Curative treatment is disappointing: only 28% of the study subjects achieved significant reductions in weight.


The sympathetic neuro-adipose connection and the control of body weight.
In recent decades, obesity has become a global public health crisis irrespective of age or gender [20]. But according to historic records, concerns over appropriate maintenance of body size have been long established. For more than to 2 millennia, the main therapeutic approach to curb excess weight has been to recommend dietary restrictions and regular exercise (Haslam, 2016). Nevertheless, more contemporary studies indicate that the employment of such approaches in the treatment of severely obese patients causes metabolic adaptions which impair their long-term success in weight management [8]. These evidences highlight thus, the urgency in the search for a more comprehensive knowledge of the mechanisms that underlie the control of body weight, which would be essential for the development of effective strategies for the treatment of obesity and its comorbidities. Importantly, the discovery of the hormone leptin [33]and the use of novel techniques in targeted transgenesis [32] have enabled progress in defining some of the key players and the molecular mechanisms that are involved in the processes that control body size homeostasis and energy balance, and how obesity may disrupt leptin's feedback loop and lead to the pathology of metabolic syndrome. On the light of such findings, here we review how the sympathetic nervous system modulates adipose tissue metabolism downstream of leptin's action on the CNS, with particular focus on how this system may be disrupted in the context of excess adiposity, plus highlight the potential clinical implications arising from a better understanding of the physiologic control of the sympathetic neuro-adipose connection.


Synthetic Cooling Agents in Australian-marketed E-cigarette Refill Liquids and Disposable E-cigarettes: Trends Follow the US Market.
E-cigarettes are becoming increasingly popular in Australia, especially amongst the younger population. The synthetic cooling molecules WS-3 and WS-23 have been identified in e-cigarette products from the US and Europe. The extent of inclusion of these synthetic coolants in Australian e-liquids is unknown, particularly in newer disposable e-cigarettes. E-cigarettes and e-liquids were purchased within Australia and anonymously donated by Australian users. Nicotine, WS-3, WS-23 and menthol were quantified in the eliquids using gas chromatography - mass spectrometry (GCMS). WS-23 and nicotine were detected in all of the disposable e-cigarettes with WS-23 often present in high concentrations. There was no correlation between cooling terms in the flavour name and the inclusion of cooling agents. Only three bottled e-liquids were found to contain WS-23 while none contained WS-3 above the limit of detection. Synthetic coolants were a common addition in disposable e-cigarettes while rarely added to e-liquid bottle refills. Their inclusion in these products is reflective of trends observed in US and European ecigarette products.


Template-based correction of high-order aberration in keratoconus.
The common change in corneal morphology that is seen in keratoconus (KC) suggests the presence of common high-order aberration (HOA) structures and the potential for HOA corrections that apply to more than one eye. The purpose of this investigation is to classify a sample of KC eyes into subgroups based on similar HOA characteristics and simulate optical performance of common HOA corrections on members of each subgroup. High-order aberrations were recorded over a 5-mm pupil on 111 KC eyes. The eyes were divided into five subgroups based on observed commonality in HOA structure. From each subgroup, two eyes were removed for later evaluation of corrections. Principal components analysis was performed on the remaining eyes of each subgroup. The first principal component was scaled to form a set of corrections. Simulated optical correction of the test eyes was performed by identifying the magnitude of the inner-group correction providing the lowest level of residual higher order root mean square wavefront error (HORMS). Residual uncorrected HORMS was compared with levels found in uncorrected normal eyes and KC eyes wearing rigid gas-permeable corrections. Ninety (81%) of the 111 eyes were included in one of the five subgroups. All 10 test eyes experienced a reduction in HORMS with a template correction compared with their uncorrected levels. Median HORMS reduced from uncorrected levels of 2.14 to 0.97 μm. On average, the 10 subjects experienced a 51% reduction in HORMS (minimum, 16%; maximum, 81%; p < 0.01). When scaled to a 4-mm pupil, five of the 10 eyes experienced residual uncorrected HORMS within limits associated with gas-permeable wear. Overlap exists across these templates because of the dominance of vertical coma in the HOA structure. All eyes evaluated received reduced HORMS with a template-based correction.


Tuning the anticancer properties of Pt(ii) complexes via structurally flexible N-(2-picolyl)salicylimine ligands.
Three tridentate Schiff base ligands were synthesized from the reactions between 2-picolylamine and salicylaldehyde derivatives (3-ethoxy (OEt), 4-diethylamino (NEt2) and 4-hydroxy (OH)). Complexes with the general formula Pt(N^N^O)Cl were obtained from reactions between the ligands and K2PtCl4. The ligands and their complexes were characterized by NMR spectroscopy, mass spectrometry and elemental analysis. Further confirmation of the structure of Pt-OEt was achieved by single-crystal X-ray diffraction. The DMSO/chlorido exchange process at Pt-OEt was investigated by monitoring the change in conductivity, revealing very slow dissociation in DMSO. Moreover, solvent/chlorido exchange for Pt-OEt and Pt-NEt2 were investigated by NMR spectroscopy in DMSO and DMSO/D2O; Pt-NEt2 forms an adduct with DMSO while Pt-OEt forms adducts with DMSO and water. The DNA-binding behaviour of the platinum(ii) complexes was investigated by two techniques. Pt-NEt2 has the best apparent binding constant. The intercalation mode of interaction with ct-DNA was suggested by molecular docking studies and the increase in the relative viscosity of ct-DNA with increasing concentrations of the platinum(ii) complexes. However, the gradual decrease in the relative viscosity over time at constant concentration of platinum(ii) complexes indicated a shift from intercalation to a covalent binding mode. Anticancer activities of the ligands and their platinum(ii) complexes were examined against two cell lines. The platinum(ii) complexes exhibit superior cytotoxicity to that of their ligands. Among the platinum(ii) complexes, Pt-OEt possesses the best IC50 against both cell lines, its cytotoxicity being comparable to that observed for cisplatin. Cell cycle arrest in the HepG2 cell line upon treatment with Pt-OEt and Pt-NEt2 was investigated and compared to that of cisplatin; the change in the cell accumulation patterns supports the presumption of an apoptotic cell death pathway. The optimized structures of the B-DNA trimer adducts with the platinum complexes showed hydrogen-bonding interactions between the ligands and nucleobases, affecting the inter-strand hydrogen bonding within the DNA, and highlighting the strong ability of the complexes to induce conformational changes in the DNA, leading to the activation of apoptotic cell death. In summary, the current study demonstrates promising new anticancer platinum(ii) complexes with highly flexible tridentate ligands; the functional groups on the ligands are important in tuning their DNA binding/anticancer properties.


Omacetaxine mepesuccinate (synribo) - newly launched in chronic myeloid leukemia.
Omacetaxine mepesuccinate (formerly known as homoharringtonine [HHT]) is a natural alkaloid with significant anticancer activity partly through inhibition of protein synthesis and induction of apoptosis. Prior to the development of tyrosine kinase inhibitors (TKIs), HHT was the most active therapy in chronic myeloid leukemia (CML) after interferon failure. Subsequent trials showed that HHT and omacetaxine are active in patients failing several TKIs or carrying the T315I mutation. This review will discuss the preclinical development of HHT and omacetaxine mepesuccinate in CML and the clinical studies leading to its approval by the Food and Drug Administration (FDA). A sizable number of patients with CML will develop TKI resistance, frequently through the acquisition of BCR-ABL1 kinase domain mutations. Omacetaxine is active in patients with CML after failure to multiple TKIs and in those carrying the T315I mutation, which is highly resistant to all FDA-approved TKIs except for ponatinib. Both ponatinib and omacetaxine have been recently approved by the FDA and represent useful treatment options for patients with CML who failed several TKIs and/or acquired the T315I mutation. The development of an oral formulation of omacetaxine would greatly facilitate its use and provide an attractive option for TKI-based combinatorial strategies.


[Acute management and face reconstruction in severe open facial injury].
Authors describe the acute treatment and the reconstruction of the face in the severe, multiple combined fracture of the facial bones. After the primary definitive care further reconstructive operations were performed. After one and half year treatment the functional and esthetic results are good.


Investigating the Role of the Hypothalamus in Outcomes to Repetitive Mild Traumatic Brain Injury: Neonatal Monosodium Glutamate Does Not Exacerbate Deficits.
Repetitive mild traumatic brain injury (RmTBI) is a prevalent and costly head injury particularly among adolescents. These injuries may result in long-term consequences, especially during this critical period of development. Insomnia and sleeping difficulties are frequently reported following RmTBI and greatly impair recovery. We sought to develop an animal model of exacerbated deficits following RmTBI by disrupting the hypothalamic circadian system. To accomplish this, we conducted RmTBI on adolescent rats that had received neonatal injections of monosodium glutamate (MSG), a known hypothalamic neurotoxin. We then examined behavioral, circadian, and epigenetic changes. MSG treated rats showed lower anxiety-like behaviors and displayed poor short-term working memory. We also showed changes in the morphology of the circadian clock in the suprachiasmatic nucleus (SCN) vasoactive intestinal polypeptide (VIP) immunostaining. VIP optical density in the SCN increased with MSG but decreased with RmTBI. There were changes in the expression of the clock genes and upregulation of the orexin receptors in response to RmTBI. MSG treated rats had longer telomere lengths than controls. Finally, although both MSG and RmTBI alone produced attenuated circadian amplitudes of activity and body temperature, exacerbated deficits were not identified in animals that received MSG and RmTBI. In sum, both MSG and RmTBI can alter behavior, circadian rhythm amplitude, SCN morphology, and gene expression independently, but the effects do not appear to be additive. Specific damage in the hypothalamus and SCN should be considered when patients experience sleeping problems following RmTBI, as this may improve therapeutic strategies.


[The mast cells phagocytose bacteria].
In the last years there has been a growing number of reports concerning the role of mast cells in host defense against bacteria. The mast cell membrane is replete with many receptors/molecules, including those that promote the recognition and binding of bacteria. Mast cells exhibit two basic mechanisms of microbial recognition: opsonin-dependent (via Fc and C3 receptors) and opsonin-independent (via integrins, CD48 molecule and Toll-like receptors). Moreover, mast cells phagocytose and kill adherent bacteria. Phagocytosis of bacteria results in the presentation of bacterial antigens for MHC class I to T cells.


Partitioned weight loss and body composition changes during a mountaineering expedition: a field study.
Weight loss and changes in body composition are recognized phenomena associated with high-altitude mountaineering expeditions. Attempts to partition the weight loss between fat mass (FM) and fat-free mass (FFM) have been inconclusive. Therefore, five male subjects, average age 40.0 +/- 5.5 years, were studied prior to, during, and following a 21-day expedition between 2200 m and 4300 m on Mt. McKinley, Alaska. Pre- to postexpedition body composition changes were determined by densitometry, skinfold thickness (12 sites), body girth measurements (14 sites), and cross-sectional area from magnetic resonance imaging (MRI) (three sites). Data analysis by Student's t-test (p < 0.05(1) tail) indicated decreases in body weight (4.2 +/- 2.8 kg, 220 g/day, 5.4% of initial weight), total skinfold thickness (10.8%), total body girth (2.8%), and percentage of fat by densitometry (15%). Total cross-sectional area of the three MRI slices (upper arm + thigh + calf) decreased 4.7%, muscle area decreased 9.1%, and fat area decreased 3.9%. The three methods used to partition the weight loss between FM and FFM did not agree: 77% FM vs 23% FFM by densitometry, 25% FM vs 75% FFM by skinfolds, and 38% FM vs 62% FFM by MRI. Energy intake (3640 +/- 1250 kcal/day) was negatively correlated (Pearson r > 0.88(2) tail) with losses in weight (r = -0.89), skinfolds (r = -0.93), and girths (r = -0.88), ie the greater the intake the less the decline. Therefore, insufficient energy intake appeared primarily responsible for the weight loss and changes in body composition during the expedition.


[Fulminant pancreatitis--internal point of view].
In acute pancreatitis pancreatic necrosis and involvement of different organ systems determine clinical course and severity. There is no method to predict the outcome of acute pancreatitis at the beginning of the disease. If there is evidence for severe pancreatitis, an immediate intensive care of all organ systems is needed, to avoid complications. Besides clinical signs, serum CRP is the most valuable parameter to define severity. According to present knowledge, a CT scan is only needed in sepsis or multiorgan failure. Non-invasive ventilation should be started early in case of hypoxia. Up to now, no general benefit was detected for antibiotic prophylaxis or enteral nutrition.


Comparison of osteogenic capability of 3D-printed bioceramic scaffolds and granules with different porosities for clinical translation.
Pore parameters, structural stability, and filler morphology of artificial implants are key factors influencing the process of bone tissue repair. However, the extent to which each of these factors contributes to bone formation in the preparation of porous bioceramics is currently unclear, with the two often being coupled. Herein, we prepared magnesium-doped wollastonite (Mg-CSi) scaffolds with 57% and 70% porosity (57-S and 70-S) via a 3D printing technique. Meanwhile, the bioceramic granules (57-G and 70-G) with curved pore topography (IWP) were prepared by physically disrupting the 57-S and 70-S scaffolds, respectively, and compared for in vivo osteogenesis at 4, 10, and 16 weeks. The pore parameters and the mechanical and biodegradable properties of different porous bioceramics were characterized systematically. The four groups of porous scaffolds and granules were then implanted into a rabbit femoral defect model to evaluate the osteogenic behavior in vivo. 2D/3D reconstruction and histological analysis showed that significant bone tissue production was visible in the central zone of porous granule groups at the early stage but bone tissue ingrowth was slower in the porous scaffold groups. The bone tissue regeneration and reconstruction capacity were stronger after 10 weeks, and the porous architecture of the 57-S scaffold was maintained stably at 16 weeks. These experimental results demonstrated that the structure-collapsed porous bioceramic is favorable for early-stage osteoconduction and that the 3D topological scaffolds may provide more structural stability for bone tissue growth for a long-term stage. These findings provide new ideas for the selection of different types of porous bioceramics for clinical bone repair.


Outcomes after minimally invasive esophagectomy: review of over 1000 patients.
Esophagectomy is a complex operation and is associated with significant morbidity and mortality. In an attempt to lower morbidity, we have adopted a minimally invasive approach to esophagectomy. Our primary objective was to evaluate the outcomes of minimally invasive esophagectomy (MIE) in a large group of patients. Our secondary objective was to compare the modified McKeown minimally invasive approach (videothoracoscopic surgery, laparoscopy, neck anastomosis [MIE-neck]) with our current approach, a modified Ivor Lewis approach (laparoscopy, videothoracoscopic surgery, chest anastomosis [MIE-chest]). We reviewed 1033 consecutive patients undergoing MIE. Elective operation was performed on 1011 patients; 22 patients with nonelective operations were excluded. Patients were stratified by surgical approach and perioperative outcomes analyzed. The primary endpoint studied was 30-day mortality. The MIE-neck was performed in 481 (48%) and MIE-Ivor Lewis in 530 (52%). Patients undergoing MIE-Ivor Lewis were operated in the current era. The median number of lymph nodes resected was 21. The operative mortality was 1.68%. Median length of stay (8 days) and ICU stay (2 days) were similar between the 2 approaches. Mortality rate was 0.9%, and recurrent nerve injury was less frequent in the Ivor Lewis MIE group (P < 0.001). MIE in our center resulted in acceptable lymph node resection, postoperative outcomes, and low mortality using either an MIE-neck or an MIE-chest approach. The MIE Ivor Lewis approach was associated with reduced recurrent laryngeal nerve injury and mortality of 0.9% and is now our preferred approach. Minimally invasive esophagectomy can be performed safely, with good results in an experienced center.


[Gayet-Wernicke encephalopathy].
We have reviewed the aetiology, symptomatology, biology and clinical course of 61 cases of the Gayet-Wernicke encephalopathy. Our results do not differ fundamentally from those of Victor et al. (1971). Nevertheless, our study shows fewer oculomotor palsies in the acute stages, lower mortality and a lower incidence of residual anmesic syndromes. These results demonstrate the importance of early diagnosis and of starting the specific therapy in the initial stage of reversible biochemical lesions.


Evaluation of sleeping energy expenditure using the SenseWear Armband in patients with overt and subclinical hypothyroidism.
The aim of the present study was to evaluate the average sleeping energy expenditure (EE) levels using the SenseWear Armband (SWA) in patients with overt and subclinical hypothyroidism. Sixty patients with hypothyroidism and 30 healthy individuals were recruited for the study. Hypothyroid patients were divided into two groups: group 1 (n = 30) consisted of patients with overt hypothyroidism and group 2 (n = 30) consisted of patients with subclinical hypothyroidism. Lastly, group 3 (n = 30) consisted of healthy subjects. The average EE and metabolic equivalent of task (MET) values during sleep of all the hypothyroid participants were analyzed at baseline and at the end of the study. Data were also obtained from the healthy subjects at baseline. The average sleeping EE and METs values were not significantly different at baseline. Similarly, these values did not change significantly after achieving a euthyroid state via thyroid hormone replacement (both p > 0.05). Contrary to what has been previously reported , the average sleeping EE and METs values in all hypothyroid patients and healthy individuals were similar at baseline and did not change in the patients with overt and subclinical hypothyroidism after achievement of a euthyroid state.


Severe cystic fibrosis associated with a deltaF508/R347H + D979A compound heterozygous genotype.
This report is concerned with twins with cystic fibrosis (CF). They are of mixed parentage: Japanese mother and German father. One case is presented with meconium ileus as a neonate. The other patient did relatively well until the age of 6 years when she was first hospitalized and diagnosed with pulmonary aspergillosis. They have been receiving standard therapies for CF including digestive enzymes, vitamins and periodic antibiotic therapy in the US. At 19 years of age, they were tested for common mutations and one AF508 cystic fibrosis transmembrane conductance regulator (CFTR) allele was found. Further testing of their CFTR gene as well as those of their Japanese mother and grandmother revealed missense mutations in exon 7 (R347H) and exon 16 (D979A). Although the D979A mutant is very rare, this mutation combination seemed to be responsible for severe CF phenotypes.


Salmonella Typhimurium exploits inflammation to its own advantage in piglets.
Salmonella Typhimurium (S. Typhimurium) is responsible for foodborne zoonotic infections that, in humans, induce self-limiting gastroenteritis. The aim of this study was to evaluate whether the wild-type strain S. Typhimurium (STM14028) is able to exploit inflammation fostering an active infection. Due to the similarity between human and porcine diseases induced by S. Typhimurium, we used piglets as a model for salmonellosis and gastrointestinal research. This study showed that STM14028 is able to efficiently colonize in vitro porcine mono-macrophages and intestinal columnar epithelial (IPEC-J2) cells, and that the colonization significantly increases with LPS pre-treatment. This increase was then reversed by inhibiting the LPS stimulation through LPS antagonist, confirming an active role of LPS stimulation in STM14028-intracellular colonization. Moreover, LPS in vivo treatment increased cytokines blood level and body temperature at 4 h post infection, which is consistent with an acute inflammatory stimulus, capable to influence the colonization of STM14028 in different organs and tissues. The present study proves for the first time that in acute enteric salmonellosis, S. Typhimurium exploits inflammation for its benefit in piglets.


Kinetics and location of bone marrow cell graft rejection by irradiated mice.
Natural killer (NK) cells were eliminated with rabbit anti-Asialo GM1 (anti-ASGM1) serum to test the kinetics and location of bone marrow cell (BMC) rejection. Anti-ASGM1 serum was injected intravenously in mice at various times before or after irradiation (8.6 Gy) and transfer of parental-strain or allogeneic BMC. Growth of BMC was determined by measuring splenic 5-iodo-2'-deoxyuridine-125I incorporation 5 days after cell transfer. Anti-ASGM1 serum weakened hybrid resistance even if injected intravenously as late as 24 h post-BMC transfer and even in recipients injected with polyinosinic:polycytidylic acid so as to boost NK activity. If regenerating spleen cells (higher rate of cell cycling) were used as donor cells instead of BMC, the length of time required for rejection was unaffected. Anti-ASGM1 serum injected intravenously rapidly inhibited splenic NK activity and lung clearance of YAC-1 tumor cells, but when injected intratracheally, it only inhibited lung NK activity. Thus, BMC rejection occurs in the hematopoietic tissue and requires at least 24 h.


Kinetics of liver function tests after a hepatectomy for colorectal liver metastases predict post-operative liver failure as defined by the International Study Group for Liver Surgery.
Post-hepatectomy liver failure (PHLF) has been defined by the International Study Group for Liver Surgery (ISGLS). The purpose of the present study was to examine the kinetics of conventional liver function tests (LFT) after a major liver resection and is the first to examine their utility in predicting PHLF in groups defined by the ISGLS. Consecutive patients undergoing a major liver resection for colorectal liver metastases were stratified into ISGLS groups and their LFT up to 1 year after surgery compared. Receiving-operating characteristic (ROC) analysis of LFT identified optimal thresholds in predicting category C liver failure. In total, 32, 22 and 19 patients belonged to ISGLS groups A, B and C, respectively. The median international normalized ratio (INR) and bilirubin values on post-operative days 1, 3, 5 and 7 were significantly different among the groups (all P-values <0.05). ROC analysis of day 1 INR (AUC 0.813) and day 5 bilirubin (AUC 0.798) revealed thresholds of 1.35 and 52 μmol/l to have sensitivities of 85% and 81% and specificities of 63% and 73%, respectively, to predict group C liver failure. Post-operative LFT after a major liver resection differs significantly among the three ISGLS groups. Thresholds of bilirubin and INR can be used to identify patients who are at a maximum risk of complications.


[A case of leiomyosarcoma of the small intestine with perforative peritonitis].
On April 15th, 1986, the patient, a 58-year-old man, felt ill because of a stomachache. On April 15, he was referred to our hospital and admitted after having been diagnosed as having pan peritonitis. During surgery, an extraintestinal growth, a small fist-size tumor, was detected in the jejunum. The tumor was partly perforated, and a partial resection of the small intestine was carried out. A histopathological examination led to the diagnosis of a leiomyosarcoma of the small intestine. On June 12, 1987, the patient again returned to our hospital, complaining of a stomachache. A reoperation was performed for perforative peritonitis due to its recurrence but only palliative treatment could be provided.


Spinal cord stimulation for relief of chronic pain in vasospastic disorders of the upper limbs.
Eleven patients with chronic pain due to severe vasospastic disorders in the upper limbs were treated with cervical spinal cord stimulation. In 8 patients the pain was due to reflex sympathetic dystrophy in the late stage of the disease, and 3 patients had severe idiopathic Raynaud's disease. The mean follow-up for both groups was 27 months. A total of 10 patients (90.9%) had good or excellent results. Thermographic and plethysmographic changes were observed in both groups. There seems to be a very close relationship between the increase of blood flow and the amount of pain relief achieved. In an attempt to quantify the intensity of pain, the visual analog scale and McGill Pain Questionnaire were used. Stimulation proved to be harmless, with no mortality and very low morbidity. The latter centered around local infection and displacement of the electrodes. No objective changes occurred in trophic alterations such as bone decalcification and ankylosis, but there were improvements in the alterations in the nails and skin. In the reflex sympathetic dystrophy group, the amount of pain relief achieved enabled most patients to undergo subsequent physiotherapy and rehabilitation. In severe cases of reflex sympathetic dystrophy and idiopathic Raynaud's disease, spinal cord stimulation is an alternative treatment that can be used as primary therapy or as secondary therapy after unsuccessful sympathectomy or sympathetic blocks.


Strategies for tobacco control among youngsters with cancer.
To examine smoking rates, discuss risk factors for smoking onset, and summarize the success of smoking trials conducted to date with youngsters treated for cancer. Studies selected from the published pediatric literature on smoking in young cancer patients were summarized to illustrate the progress in tobacco control in this vulnerable population. Children with cancer report smoking at rates that are lower than or comparable to those of their healthy peers, depending on their treatment status. The few smoking trials conducted with youngsters with cancer have yielded modest effects. The timing, intensity and duration of smoking interventions for children with cancer in the medical setting have not been adequately explored. Identification of intermediate biomarkers that are predictive of later morbidity is necessary to demonstrate the short-term impact of smoking trials. Simultaneous implementation of many levels of intervention will enhance tobacco control efforts for youngsters with cancer.


Fitting meta-analytic structural equation models with complex datasets.
A modification of the first stage of the standard procedure for two-stage meta-analytic structural equation modeling for use with large complex datasets is presented. This modification addresses two common problems that arise in such meta-analyses: (a) primary studies that provide multiple measures of the same construct and (b) the correlation coefficients that exhibit substantial heterogeneity, some of which obscures the relationships between the constructs of interest or undermines the comparability of the correlations across the cells. One component of this approach is a three-level random effects model capable of synthesizing a pooled correlation matrix with dependent correlation coefficients. Another component is a meta-regression that can be used to generate covariate-adjusted correlation coefficients that reduce the influence of selected unevenly distributed moderator variables. A non-technical presentation of these techniques is given, along with an illustration of the procedures with a meta-analytic dataset. Copyright © 2016 John Wiley & Sons, Ltd.


The influence of operating experiences in the design of the IVAR thermal drying plant expansion in Stavanger, Norway.
The Regional Wastewater Treatment Plant of North Jaeren (IVAR IKS) serves the Stavanger conurbation with a population equivalence of 240,000. The site was the first in Norway to operate a thermal drying and a pelletising plant for municipal sludge. Since the start up in 1992, IVAR has encountered most of the operational problems typically associated with thermal drying processes. Considerable modifications have been made and lessons learnt resulting in the plant being one of the few thermal drying facilities in Norway which continues to operate successfully. In general, thermal drying is often considered as a costly, energy demanding and complex process requiring careful attention to safety aspects such as risks of self-combustion, fires and dust explosions. The paper presents general considerations of operating experiences influencing the procurement and design stage of the new extended IVAR thermal drying plant. Furthermore, topical issues important for resolution of thermal drying problems are also discussed. Mass and energy balances for the Stavanger plant are presented.


ETV6-related thrombocytopenia and leukemia predisposition.
Germ line mutations in ETV6 are responsible for a familial thrombocytopenia and leukemia predisposition syndrome. Thrombocytopenia is almost completely penetrant and is usually mild. Leukemia is reported in ∼30% of carriers and is most often B-cell acute lymphoblastic leukemia. The mechanisms by which ETV6 dysfunction promotes thrombocytopenia and leukemia remain unclear. Care for individuals with ETV6-related thrombocytopenia and leukemia predisposition includes genetic counseling, treatment or prevention of excessive bleeding and surveillance for the development of hematologic malignancy.


Cerebral calcifications and cerebellar hypoplasia in two children: clinical, radiologic and neuropathological studies--a separate neurodevelopmental entity.
Two siblings with cerebral calcifications are described, clinically characterized by the early onset of general regression and epileptic seizures, followed by cerebral blindness and spastic tetraplegia. No remarkable biochemical abnormalities were found. Death ensued before the age of seven years. Radiology of the skull in the second case showed widespread calcifications, situated periventricularly, in the basal nuclei and in the cerebellum. In both cases postmortem examination revealed widespread calcifications, corpus callosum hypoplasia and hydrocephalus "a vacuo". Moreover retrocerebellar leptomeningeal "cysts" and hypoplasia of the cerebellum were found. A diffuse lack of axons appeared to be the main cause of the poor staining of the white matter. The diagnostic criteria are neurological regression, progressive calcification, hydrocephalus and hypoplasia of the corpus callosum and cerebellum. Five similar cases were found in the literature. Our cases and those from the literature probably belong to a separate entity, originally published by Laubenthal et al (1940).


Analysis of glycoproteins expressed by isolates of herpes simplex virus causing different forms of keratitis in man.
An in vitro analysis of glycoprotein produced by nine human ocular isolates of HSV-1 is reported. The source of the isolates was; three patients with recurrent dendritic keratitis, three with chronic stromal disease and three with primary keratoconjunctivitis. Virus strains were labelled with the radioactive precursors (35S) methionine and (14C) glucosamine. Radiolabelled viral glycoproteins were subsequently analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), followed by autoradiography. Viral glycoproteins were further characterised by immuno-precipitation with polyclonal and monoclonal antibodies to HSV. The stromal isolates excrete larger amounts of 'soluble' precursor glycoprotein D than those in the other two disease categories. It is possible that the immune response to glycoprotein D is in part responsible for the severity of stromal disease.


The [5+5] route to the phenanthrene skeleton.
This account describes the historical development of the coupling of γ,δ-unsaturated Fischer carbene complexes and o-alkynylbenzaldehydes, which directly affords hydrophenanthrene ring systems in a process where each reactant contributes five carbons to the newly-formed bicyclo[4.4.0]decane ring system. The process has been termed net [5+5] cycloaddition. Use of the reaction to produce various medicinally important natural products and/or their parent ring systems is discussed.


Identification of Pulmonary Edema in Forensic Autopsy Cases of Sudden Cardiac Death Using Fourier Transform Infrared Microspectroscopy: A Pilot Study.
Many studies have proven the usefulness of biofluid-based infrared spectroscopy in the clinical domain for diagnosis and monitoring the progression of diseases. Here we present a state-of-the-art study in the forensic field that employed Fourier transform infrared microspectroscopy for postmortem diagnosis of sudden cardiac death (SCD) by in situ biochemical investigation of alveolar edema fluid in lung tissue sections. The results of amide-related spectral absorbance analysis demonstrated that the pulmonary edema fluid of the SCD group was richer in protein components than that of the neurologic catastrophe (NC) and lethal multiple injuries (LMI) groups. The complementary results of unsupervised principle component analysis (PCA) and genetic algorithm-guided partial least-squares discriminant analysis (GA-PLS-DA) further indicated different global spectral band patterns of pulmonary edema fluids between these three groups. Ultimately, a random forest (RF) classification model for postmortem diagnosis of SCD was built and achieved good sensitivity and specificity scores of 97.3% and 95.5%, respectively. Classification predictions of unknown pulmonary edema fluid collected from 16 cases were also performed by the model, resulting in 100% correct discrimination. This pilot study demonstrates that FTIR microspectroscopy in combination with chemometrics has the potential to be an effective aid for postmortem diagnosis of SCD.


Improved and new-onset anemia during follow-up in patients with acute decompensated heart failure: Characteristics and outcomes.
There was no previous report on the prognostic impact of new-onset or improved anemia after discharge from acute decompensated heart failure (ADHF).We analyzed 771 patients with ADHF and who were followed in multicenters in Japan was divided into 4 groups based on the hemoglobin values at discharge and 6-month index visit: 373 patients (48.4%) with persistent anemia, 87 patients (11.3%) with new-onset anemia, 91 patients (11.8%) with improved anemia, and 220 patients (28.5%) without anemia.The primary outcome measure was a composite of all-cause death or HF hospitalization after index visit. The cumulative 6-month incidences of the primary outcome measure were 25.2% for persistent anemia, 18.5% for new onset anemia, 9.0% for improved anemia, and 9.2% for no anemia (log-rank P < .001). Compared with the no anemia group, the excess risk for the primary outcome measure remained significant in the persistent anemia group [hazard ratio (HR) 2.70, 95% confidence interval (95% CI), 1.45-5.44, P = .001] and in the new-onset anemia group (HR 2.73, 95% CI 1.19-6.25, P = .02), while it was not significant in the improved anemia group (HR 1.69, 95% CI 0.68-4.03, P = .25).Persistent and new-onset anemia at 6-month visit were associated with a subsequent higher risk for all-cause death or HF hospitalization in patients with ADHF, suggesting the importance of detecting anemia during follow-up.


Eye Contact Judgment Is Influenced by Perceivers' Social Anxiety But Not by Their Affective State.
Fast and accurate judgment of whether another person is making eye contact or not is crucial for our social interaction. As affective states have been shown to influence social perceptions and judgments, we investigated the influence of observers' own affective states and trait anxiety on their eye contact judgments. In two experiments, participants were required to judge whether animated faces (Experiment 1) and real faces (Experiment 2) with varying gaze angles were looking at them or not. Participants performed the task in pleasant, neutral, and unpleasant odor conditions. The results from two experiments showed that eye contact judgments were not modulated by observers' affective state, yet participants with higher levels of social anxiety accepted a wider range of gaze deviations from the direct gaze as eye contact. We conclude that gaze direction judgments depend on individual differences in affective predispositions, yet they are not amenable to situational affective influences.


Effects of sex and gender on adaptations to space: reproductive health.
In this report, sex/gender research relevant to reproduction on Earth, in conjunction with the extant human and animal observations in space, was used to identify knowledge gaps and prioritize recommendations for future sex- and gender-specific surveillance and monitoring of male and female astronauts. With overall increased durations of contemporary space missions, a deeper understanding of sex/gender effects on reproduction-related responses and adaptations to the space environment is warranted to minimize risks and insure healthy aging of the men and women who travel into space.


Adolescents' Utilization of a Tertiary-Level Pediatric Emergency Department in Italy.
Describe the use of the emergency department of a tertiary-level children's hospital in Italy by adolescents. This retrospective study was based on the medical records of patients aged 13 to 17 years, who accessed the emergency department of the Institute for Maternal and Child Health of Trieste, from 1 January to 31 December 2018. The primary outcome was to describe the leading causes of access, diagnoses, rate of hospitalization, and ward of destination among adolescent patients. During the study period, 24,599 patients accessed the department. Among them, 3,062 were adolescents, for a total of 3,895 unscheduled visits. The principal causes of access were trauma (45.3%) and organic diseases (38.8%). Two hundred and forty nine adolescents (6.4%) had mental health problems. One hundred and forty two adolescents (3.6%) Were Admitted to the Hospital, 54 of Whom (38%) to the Neuropsychiatric Ward, for Mental Health Problems. Among adolescents seen in this Italian tertiary-level children's hospital, mental health problems represented a small proportion of emergency department visits but were the leading cause of urgent hospitalization.