Ultrasound visualization of the vagus nerve for intraoperative neuromonitoring in thyroid surgery.
Localization of the vagus nerve is required during intraoperative neuromonitoring (IONM) for thyroid surgery in order to electromyographically verify the functional integrity of inferior laryngeal nerve and aim to reduce the risk of postoperative vocal fold paralysis. Classically, the vagus nerve courses within the carotid sheath between the common carotid artery and internal jugular vein, but anatomic variations have been described. Our aim was to compare preoperative ultrasound (US) and intraoperative localization of vagus nerve and to document anatomic variations. Retrospective study of patients undergoing thyroidectomy. The vagus nerve was identified 2 cm below the inferior border of the cricoid cartilage, on US performed 6 weeks prior to surgery; then, vagus nerve was identified surgically. For 82 patients, on preoperative US, the right vagus nerve was in between, superficial, or deep to the vessels in 94%, 2.4%, and 3.6%, and on the left in 72%, 24.4%, and 3.6%. Intraoperatively, the right vagus was in between, superficial, or deep in 90%, 4%, and 6%, and on the left in 67%, 27%, and 6%. US correlated with surgery on the right in 79/82 (96%) and on the left in 78/82 (95%). To our knowledge, this is the first study directly comparing US and intraoperative findings. The US and surgical findings were identical in 95% on the left and 96% on the right The vagus nerve was superficial in 27% of cases on the left and 4% on the right. Identifying this anatomic variation preoperatively may facilitate IONM. • Localization of the vagus nerve is necessary during thyroid surgery when using neuromonitoring for electromyographic testing of the inferior laryngeal nerve to reduce the risk of postoperative vocal fold paralysis. • The vagus nerve in the neck can be routinely visualized using ultrasound, and is generally in between the common carotid artery and the internal jugular vein. Its location on ultrasound corresponds very closely to that observed in vivo during surgery (95%). • At the level of the thyroid lobe, there is an anatomic variant with the vagus nerve superficial to the common carotid artery which is seen more often on the left than on the right.


Classic myeloproliferative neoplasms in Singapore: A population-based study on incidence, trends, and survival from 1968 to 2017.
Current descriptive epidemiological information on classic myeloproliferative neoplasms (MPNs) is incomplete. Published data among Asian population are particularly sparse. We conducted a large population-based study to determine the incidence rates and survival patterns of MPN reported to the Singapore Cancer Registry during the period 1968-2017. Age-standardised incidence rates(ASR), overall survival, 5-/10-year relative survival ratio (RSR) were estimated. Joinpoint regression was used to evaluate quinquennial percent change (QPC) in incidence. We identified 2557 individuals diagnosed with MPN including 1031 chronic myeloid leukaemia (CML), 424 polycythaemia vera (PV), 389 essential thrombocythaemia (ET), 134 primary myelofibrosis (PMF) and 579 MPN unclassifiable (MPN-U). The overall respective ASRs per 100,000 for CML, PV, ET, PMF and MPN-U were 1.24, 1.15, 1.07, 0.43, and 0.80 in 2013-2017. Males had higher ASR than females in all MPNs. A gradual rise in incidence trends of CML was observed between 1968 and 2017 (QPC 2.1%, 95% CI -0.9, 5.3). The overall incidence trends of non-CML MPNs including PV (QPC 62.9%, 95% CI 19.3, 122.6), ET (QPC 54.2%, 95% CI 23.5, 92.3) and PMF (QPC 103.5%, 95% CI 19.1, 247.6) increased sharply during 1993-2017. Survival was lower in MPNs compared with expected survival in general population: 5-year RSRs were 0.82 (95% CI 0.78, 0.86), 0.96 (95% CI 0.91, 1.01), 0.96 (95% CI 0.92, 1.01), 0.53 (95% CI 0.43, 0.65), and 0.74 (95% CI 0.68, 0.80) for CML, PV, ET, PMF and MPN-U respectively. CML incidence has increased marginally, whereas non-CML MPNs incidences have sharply increased. MPN patients have a lower relative survival compared to the general population, and patients with PV and ET have the most favourable relative survival. Median survival for CML patients has increased dramatically over the last 50 years.


Lipid-based vaccine nanoparticles for induction of humoral immune responses against HIV-1 and SARS-CoV-2.
The current health crisis of corona virus disease 2019 (COVID-19) highlights the urgent need for vaccine systems that can generate potent and protective immune responses. Protein vaccines are safe, but conventional approaches for protein-based vaccines often fail to elicit potent and long-lasting immune responses. Nanoparticle vaccines designed to co-deliver protein antigens and adjuvants can promote their delivery to antigen-presenting cells and improve immunogenicity. However, it remains challenging to develop vaccine nanoparticles that can preserve and present conformational epitopes of protein antigens for induction of neutralizing antibody responses. Here, we have designed a new lipid-based nanoparticle vaccine platform (NVP) that presents viral proteins (HIV-1 and SARS-CoV-2 antigens) in a conformational manner for induction of antigen-specific antibody responses. We show that NVP was readily taken up by dendritic cells (DCs) and promoted DC maturation and antigen presentation. NVP loaded with BG505.SOSIP.664 (SOSIP) or SARS-CoV-2 receptor-binding domain (RBD) was readily recognized by neutralizing antibodies, indicating the conformational display of antigens on the surfaces of NVP. Rabbits immunized with SOSIP-NVP elicited strong neutralizing antibody responses against HIV-1. Furthermore, mice immunized with RBD-NVP induced robust and long-lasting antibody responses against RBD from SARS-CoV-2. These results suggest that NVP is a promising platform technology for vaccination against infectious pathogens.


β-Glucanase specific expression in the parotid gland of transgenic mice.
The feasibility of using the pig parotid secretory protein promoter to drive the β-glucanase transgene expression in mouse parotid glands was examined in this study. The parotid gland-specific vector expressing β-glucanase gene (GLU, from Paenibacillus polymyxa CP7) was constructed. Transgenic mice were produced by the pronuclear microinjection. Both PCR and Southern blot analysis showed that the mice carried the β-glucanase gene and the β-glucanase gene could be stably inherited. Furthermore, RT-PCR and northern blot analysis indicated that it was specifically expressed in the parotid. The β-glucanase activity in the saliva was found to be 0.18 U/mL. After feeding a diet containing 2 % β-glucan, the average daily gain of transgenic was significantly higher than non-transgenic mice. The crude protein and crude fat concentration in faeces of transgenic mice were significantly reduced compared with that of the non-transgenic mice. These results suggest that the successful expression of foreign β-glucanase in the animal parotid would offer a promising biological approach to reduce the anti-nutritional effect of β-glucans in feed.


Evaluating non-pharmacological approaches to nursing home dementia care: A protocol.
The COVID-19 pandemic has underscored the daily challenges nursing home (NH) staff face caring for the residents living with Alzheimer's Disease and Related Dementias (ADRD). Non-pharmacological approaches are prioritized over off-label medication to manage the behavioral and psychological symptoms of ADRD. Yet, it is not clear how to best equip NH staff and families with the knowledge and strategies needed to provide non-pharmacological approaches to these residents. This clustered randomized trial will compare team- and problem-based approaches to non-pharmacological ADRD care. The team-based approach includes core training for all NH staff using a common language and strategies to support continuity and sustainability. The problem-based approach capitalizes on the expertise of the professional healthcare providers to target issues that arise. A convergent mixed methods design will be used to examine (a) comparative effectiveness of the two approaches on long-term NH resident outcomes and (b) whether either approach is protective against the negative consequences of COVID-19. The primary outcome is the percentage of ADRD residents with off-label antipsychotic medication use, which will be evaluated with an intent-to-treat approach. Staff and family caregiver perspectives will be explored using a multiple case study approach. This trial will be the first-ever evaluation of team- and problem-based approaches to ADRD care across multiple NHs and geographic regions. Results can provide health system leaders and policymakers with evidence on how to optimize ADRD training for staff in an effort to enhance ADRD care delivery.


Measuring the nonselective effects of motor inhibition using isometric force recordings.
Inhibition is a key cognitive control mechanism humans use to enable goal-directed behavior. When rapidly exerted, inhibitory control has broad, nonselective motor effects, typically demonstrated using corticospinal excitability measurements (CSE) elicited by transcranial magnetic stimulation (TMS). For example, during rapid action-stopping, CSE is suppressed at both stopped and task-unrelated muscles. While such TMS-based CSE measurements have provided crucial insights into the fronto-basal ganglia circuitry underlying inhibitory control, they have several downsides. TMS is contraindicated in many populations (e.g., epilepsy or deep-brain stimulation patients), has limited temporal resolution, produces distracting auditory and haptic stimulation, is difficult to combine with other imaging methods, and necessitates expensive, immobile equipment. Here, we attempted to measure the nonselective motor effects of inhibitory control using a method unaffected by these shortcomings. Thirty male and female human participants exerted isometric force on a high-precision handheld force transducer while performing a foot-response stop-signal task. Indeed, when foot movements were successfully stopped, force output at the task-irrelevant hand was suppressed as well. Moreover, this nonselective reduction of isometric force was highly correlated with stop-signal performance and showed frequency dynamics similar to established inhibitory signatures typically found in neural and muscle recordings. Together, these findings demonstrate that isometric force recordings can reliably capture the nonselective effects of motor inhibition, opening the door to many applications that are hard or impossible to realize with TMS.


Immobilization of enzymes on nanoinorganic support materials: An update.
Despite the widespread use in various industries, enzyme's instability and non-reusability limit their applications which can be overcome by immobilization. The nature of the enzyme's support material and method of immobilization affect activity, stability, and kinetics properties of enzymes. Here, we report a comparative study of the effects of inorganic support materials on immobilized enzymes. Accordingly, immobilization of enzymes on nanoinorganic support materials significantly improved thermal and pH stability. Furthermore, immobilizations of enzymes on the materials mainly increased Km values while decreased the Vmax values of enzymes. Immobilized enzymes on nanoinorganic support materials showed the increase in ΔG value, and decrease in both ΔH and ΔS values. In contrast to weak physical adsorption immobilization, covalently-bound and multipoint-attached immobilized enzymes do not release from the support surface to contaminate the product and thus the cost is decreased while the product quality is increased. Nevertheless, nanomaterials can enter the environment and increase health and environmental risks and should be used cautiously. Altogether, it can be predicated that hybrid support materials, directed immobilization methods, site-directed mutagenesis, recombinant fusion protein technology, green nanomaterials and trailor-made supports will be used increasingly to produce more efficient immobilized industrial enzymes in near future.


Sudden infant death syndrome: an update and new perspectives of etiology.
Sudden infant death syndrome (SIDS) is a condition in which an infant, usually in the early postnatal period and nearly always before 6 months of age, dies during sleep for unexplained reasons and the standard autopsy fails to disclose an etiology. Various physiological explanations of risk factors include the prone sleeping position, overheating by excessive bundling, viral upper respiratory tract infections, parental smoking at home, and birthing injury resulting in an insult to the inner ear and central chemoreceptor zone, an immaturity that involves CO2 chemoreceptors that regulate respiratory control. Neuropathological studies and theories implicate: (1) hypoplasia or defective transmitter function in the medullary arcuate nucleus, a derivative of the rhombencephalic lip of His; (2) synaptic or receptor immaturity of the nucleus of the fasciculus solitarius, the "pneumotaxic center"; and (3) functional impairment of the serotonergic raphé nuclei of the pontine and medullary ventral median septum and other serotonergic neurons of the brainstem. Additional neurological risk factors for SIDS include perinatal neuromuscular diseases, infantile epilepsies or status epilepticus, and genetic metabolic encephalopathies.


The methyl binding domain 3/nucleosome remodelling and deacetylase complex regulates neural cell fate determination and terminal differentiation in the cerebral cortex.
Chromatin-modifying complexes have key roles in regulating various aspects of neural stem cell biology, including self-renewal and neurogenesis. The methyl binding domain 3/nucleosome remodelling and deacetylation (MBD3/NuRD) co-repressor complex facilitates lineage commitment of pluripotent cells in early mouse embryos and is important for stem cell homeostasis in blood and skin, but its function in neurogenesis had not been described. Here, we show for the first time that MBD3/NuRD function is essential for normal neurogenesis in mice. Deletion of MBD3, a structural component of the NuRD complex, in the developing mouse central nervous system resulted in reduced cortical thickness, defects in the proper specification of cortical projection neuron subtypes and neonatal lethality. These phenotypes are due to alterations in PAX6+ apical progenitor cell outputs, as well as aberrant terminal neuronal differentiation programmes of cortical plate neurons. Normal numbers of PAX6+ apical neural progenitor cells were generated in the MBD3/NuRD-mutant cortex; however, the PAX6+ apical progenitor cells generate EOMES+ basal progenitor cells in reduced numbers. Cortical progenitor cells lacking MBD3/NuRD activity generate neurons that express both deep- and upper-layer markers. Using laser capture microdissection, gene expression profiling and chromatin immunoprecipitation, we provide evidence that MBD3/NuRD functions to control gene expression patterns during neural development. Our data suggest that although MBD3/NuRD is not required for neural stem cell lineage commitment, it is required to repress inappropriate transcription in both progenitor cells and neurons to facilitate appropriate cell lineage choice and differentiation programmes.


Renal abnormalities among children with sickle cell conditions in highly resource-limited setting in Ghana.
Sickle cell disease (SCD) is associated with progressive multi-organ failure especially, the brain and kidney and leads to high morbidity and mortality rate. The aim of this study was to determine the prevalence of renal abnormalities among children with SCD. This cross-sectional study recruited 212 sickling positive patients comprising of 96 Hb AS, 48 Hb SC, and 68 Hb SS phenotypes from the Pediatric Unit of Wassa Akropong Government Hospital, Wassa Akropong, Ghana. Early morning urine and venous blood samples were collected from each participant. Urinalysis was conducted and serum urea and creatinine levels were estimated. Estimate glomerular filtration rate (eGFR) was calculated using the Swartz equation. Classification of chronic kidney disease (CKD) was based on 'The Kidney Disease: Improving Global Outcomes (KIDIGO)' criteria. The mean age of the children were 7.90 years. Serum creatinine (p = 0.0310) and urea (p<0.0001) levels were significantly higher among Hb AS participants compared with Hb SS phenotype. The prevalent indicators of renal abnormalities were proteinuria (26.4%), urine granular cast (5.6%) and CKD (39.6%). Proteinuria, urine granular cast and CKD were most prevalent among Hb SS (47.1%, 11.8% and 73.5% respectively) compared with Hb SC (41.7%, 8.3%, and 45.8% respectively) and Hb AS (4.2%, 0.0%, and 14.5%) phenotypes, respectively. Sickle cell conditions were significantly associated with proteinuria (p<0.0001) and CKD (p = 0.0378). Children with Hb SS [aOR = 5.04, 95% CI (2.47-10.3); p<0.0001] and Hb SC [aOR = 3.14 95% CI (1.39-7.01); p = 0.0174] were at increased odds of developing CKD after adjusting for age, BMI and gender. Proteinuria and CKD are associated with sickle cell disease (Hb SC and Hb SS). Renal function should be routinely monitored for children with SCD.


Targeted Selection of Stimulation Parameters for Restoration of Motor and Autonomic Function in Individuals With Spinal Cord Injury.
This is a report of methods and tools for selection of task and individual configurations targeted for voluntary movement, standing, stepping, blood pressure stabilization, and facilitation of bladder storage and emptying using tonic-interleaved excitation of the lumbosacral spinal cord. This study aimed to present strategies used for selection of stimulation parameters for various motor and autonomic functions. Tonic-interleaved functionally focused neuromodulation targets a myriad of consequences from spinal cord injury with surgical implantation of the epidural electrode at a single location. This approach indicates the sophistication of the human spinal cord circuitry and its important role in the regulation of motor and autonomic functions in humans.


Mapping the optimal forest road network based on the multicriteria evaluation technique: the case study of Mediterranean Island of Thassos in Greece.
The sustainable management of forest resources can only be achieved through a well-organized road network designed with the optimal spatial planning and the minimum environmental impacts. This paper describes the spatial layout mapping for the optimal forest road network and the environmental impacts evaluation that are caused to the natural environment based on the multicriteria evaluation (MCE) technique at the Mediterranean island of Thassos in Greece. Data analysis and its presentation are achieved through a spatial decision support system using the MCE method with the contribution of geographic information systems (GIS). With the use of the MCE technique, we evaluated the human impact intensity to the forest ecosystem as well as the ecosystem's absorption from the impacts that are caused from the forest roads' construction. For the human impact intensity evaluation, the criteria that were used are as follows: the forest's protection percentage, the forest road density, the applied skidding means (with either the use of tractors or the cable logging systems in timber skidding), the timber skidding direction, the visitors' number and truck load, the distance between forest roads and streams, the distance between forest roads and the forest boundaries, and the probability that the forest roads are located on sights with unstable soils. In addition, for the ecosystem's absorption evaluation, we used forestry, topographical, and social criteria. The recommended MCE technique which is described in this study provides a powerful, useful, and easy-to-use implement in order to combine the sustainable utilization of natural resources and the environmental protection in Mediterranean ecosystems.


Occurrence of multiple mental health or substance use outcomes among bisexuals: a respondent-driven sampling study.
Bisexual populations have higher prevalence of depression, anxiety, suicidality and substance use than heterosexuals, and often than gay men or lesbians. The co-occurrence of multiple outcomes has rarely been studied. Data were collected from 405 bisexuals using respondent-driven sampling. Weighted analyses were conducted for 387 with outcome data. Multiple outcomes were defined as 3 or more of: depression, anxiety, suicide ideation, problematic alcohol use, or polysubstance use. Among bisexuals, 19.0 % had multiple outcomes. We did not find variation in raw frequency of multiple outcomes across sociodemographic variables (e.g. gender, age). After adjustment, gender and sexual orientation identity were associated, with transgender women and those identifying as bisexual only more likely to have multiple outcomes. Social equity factors had a strong impact in both crude and adjusted analysis: controlling for other factors, high mental health/substance use burden was associated with greater discrimination (prevalence risk ratio (PRR) = 5.71; 95 % CI: 2.08, 15.63) and lower education (PRR = 2.41; 95 % CI: 1.06, 5.49), while higher income-to-needs ratio was protective (PRR = 0.44; 0.20, 1.00). Mental health and substance use outcomes with high prevalence among bisexuals frequently co-occurred. We find some support for the theory that these multiple outcomes represent a syndemic, defined as co-occurring and mutually reinforcing adverse outcomes driven by social inequity.


Serum Estradiol Correlates With Benign Paroxysmal Positional Vertigo in Postmenopausal Women.
A high incidence of benign paroxysmal positional vertigo (BPPV) is reported in postmenopausal women, and the association between estradiol (E2) deficiency and the occurrence of BPPV was investigated. Postmenopausal women with and without BPPV were included from 2016 to 2019, and 1-year follow-up was performed. Serum otolin-1 and E2 levels were assayed before the canalith repositioning treatment. Bone mineral density (BMD) was measured with a dual-energy x-ray absorptiometry scan. Receiver operating characteristic analysis was performed to determine the occurrence of BPPV, and Pearson analysis was performed to indicate the correlation between E2, otolin-1, and BMD. Eighty-six postmenopausal women with BPPV and 80 age-, demographics-, and clinical characteristics-matched normal postmenopausal women were enrolled. Decreased E2 levels, increased otolin-1 levels, and decreased BMD were observed in postmenopausal women with BPPV, and increased BMD and decreased otolin-1 levels were observed in patients with higher levels of serum E2. Receiver operating characteristic analysis revealed that E2, otolin-1, and BMD showed low sensitivity and moderate specificity to determine the occurrence of BPPV. On the other hand, a low correlation coefficient was found between E2 and otolin-1, or BMD. It is worth noting that low E2 levels were found in the relapsed patients with BPPV after a 1-year follow-up. E2 deficiency is correlated with the occurrence of BPPV, which may be a potential risk biomarker for postmenopausal women.


Growth inhibitory effect of juvenile hormone analogues on epimastigotes of Trypanosoma cruzi.
Several compounds, structurally related to the insect growth regulator Fenoxycarb, exhibited interesting inhibition action to control proliferation of Trypanosoma cruzi, the parasite responsible for Chagas' disease. Some of these drugs were shown to be potent growth inhibitors of this parasite. All of these drugs had previously presented juvenoid activity on several non-related bug species such as Tenebrio molitor, Galleria mellonella, Dysdercus cingulatos, and Pyrrhocoris apterus.


Dual energy CT in the management of antiplatelet therapy in patients with acute ischemic stroke for carotid obstruction.
Acute tandem occlusions often require carotid stenting. Combination of mechanical and pharmacologic therapies in addition to antiplatelet drugs administered to prevent acute stent thrombosis might increase the risk of intracerebral hemorrhage. We present a protocol of antiplatelet regimen based on early post-procedural dual-energy CT (DE-CT). Fifty consecutive stroke patients with tandem occlusions treated with acute carotid stenting after intracranial thrombectomy and TICI 2b/3 were reviewed. All patients received intravenous lysine acetylsalicylate during the procedure. Dual (aspirin+clopidogrel with or without clopidogrel load, groups A and B, respectively) or mono (aspirin) antiplatelet regimen (group C) was administered 12-24 h later according to brain DE-CT findings. Carotid ultrasonography was performed at 24 h and before discharge. We evaluated the rate of subsequent symptomatic intracranial hemorrhage (SICH) and acute stent thrombosis in each group. Between June 2014 and December 2016, 50 patients were included (mean age 66 years, 76% men, baseline NIHSS 16, median time from symptom onset to recanalization 266 min). According to DE-CT, 24 patients were assigned to group A, 19 to group B and 7 to group C (4 of them had SICH at that time). One patient suffered a subsequent SICH (belonging to group B). There was only one stent thrombosis without clinical repercussions in group B. DE-CT may contribute to select antiplatelet regimen after acute carotid stenting in tandem occlusions.


Mobilization of peripheral blood stem cells in children using G-CSF after carboplatin containing myelosuppressive chemotherapy.
Peripheral blood stem cell (PBSC) apheresis provides an alternative to autologous marrow harvest as a source of hematologic stem cells for transplantation in children with solid tumors. Eight children with metastatic or recurrent solid tumors underwent 27 apheresis procedures. Recovery from myelosuppressive chemotherapy occurred without continuous daily growth factor support prior to mobilization. Granulocyte colony stimulating factor (G-CSF) at 16 microgs/kg/day was used to increase stem cells in the peripheral circulation. CD 34 positive cells, mononuclear cells (MNC), and CFU-GM were measured in the apheresis products. Prior chemotherapy was examined as a clinical factor that affected PBSC yield. A significant correlation was found between CD 34+/kg and CFU-GM/kg of the products (r = 0.758, P < 0.001). Patients receiving cumulative doses of carboplatin over 1,600 mg/m2 produced adequate MNC (1 x 10(8)/kg) but yielded significantly less CD 34+ cells or CFU-GM than those patients receiving less carboplatin. Prior doses of etoposide and ifosfamide did not effect PBSC yield. The mobilization technique was well tolerated, and the products obtained produced trilineage engraftment in the patients that underwent peripheral blood stem cell transplantation. Peripheral blood stem cell apheresis in children can be optimized by selection of appropriate candidates and mobilization with G-CSF after an absence of hematopoietic growth factor support.


The system design of atrazine oxidation by catalytic oxidation process through a kinetic approach.
A design method for the removal of atrazine (ATZ) by catalytic oxidation process (COP) was developed though examination of the reaction kinetics in various conditions. The reaction kinetics of ATZ decay in COP are found to consist of a reaction and a stagnant stage, while two characteristic constants, the initial decay rate and the oxidative capacity of the COP, are successfully derived and used to describe the two stages, respectively. The proposed model and the way to solve the two characteristic constants (the initial decay rate and the oxidative capacity) are capable of describing the ATZ degradation precisely in COP at different Fe(II) concentrations and [Fe(II)]/[H(2)O(2)] ratios, where the marginal [Fe(II)]/[ATZ] ratio at 10 is found to be the critical point to achieve a cost-effective treatment of ATZ by COP. A series of equations for practical completely mixed batch reactor design is also developed based on the two characteristic constants.


Association of IL10 gene promoter polymorphisms with risks of gastric cancer and atrophic gastritis.
To investigate the association between polymorphisms of the interleukin 10 ( IL10) gene and risk of gastric cancer (GC) and atrophic gastritis (AG). This study enrolled patients with GC, patients with AG and healthy control subjects. Demographic data were collected and the IL10 gene -1082A/G, -819C/T and -592A/C polymorphisms were genotyped. An enzyme-linked immunosorbent assay was performed to detect Helicobacter pylori infection. The study enrolled 556 participants including 208 in the GC group, 116 in the AG group and 232 controls (CON group). In a recessive model of the IL10-819C/T polymorphism, a significantly decreased risk of GC was found compared with AG and non-cancer subjects, respectively (AG→GC: odds ratio OR 0.41; non-cancer→GC: OR 0.57). The CC genotype demonstrated a significantly increased risk of AG compared with CON. Similar significant results were detected in males and H. pylori-negative subgroups. The ACC haplotype was associated with a decreased risk of GC compared with AG. The ATC haplotype was associated with a decreased risk of AG compared with the CON group, but it was associated with an increased risk of GC compared with AG. The IL10 gene promoter -819C/T (rs1800871) polymorphism was associated with the risk of GC and AG in a Chinese population.


Complete Genome Sequence of Tissierella sp. Strain Yu-01, Isolated from the Feces of the Black Soldier Fly.
We report the complete genome sequence of Tissierella sp. strain Yu-01 (=BCRC 81391), isolated from the feces of black soldier fly (Hermetia illucens) larvae. This fly has increasingly been gaining attention because of its usefulness for recycling organic waste. The genome of strain Yu-01 was selected for further species delineation.


Prevalence of Olfactory Dysfuntion in SARS-COV-2 Positive Patients.
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is associated with chemosensory symptoms including olfactory dysfunction and dysgeusia. Multiple studies have reported differing prevalence rates of symptoms and recovery rates depending on geographic location. The purpose of the study was to determine the prevalence and features of Covid19 olfactory dysfunction in a developing nation. We conducted a prospective study at a tertiary, high-volume centre in South Africa, to determine the prevalence of olfactory dysfunction in SARS-COV-2 positive patients. The average recovery time of the olfactory dysfunction was also evaluated. The study included patients diagnosed with SARS-COV-2 infection between November 2020 and January 2021. Patients were recruited to participate in a survey which assessed demographic data, date of diagnosis, initial symptoms, presence and recovery time of olfactory dysfunction symptoms. A total of 86 patients with olfactory dysfunction were included and followed up telephonically over 6 weeks in 2 week intervals to determine recovery time. There was a prevalence rate of 40.7% of olfactory dysfunction in patients in our study. A higher proportion of patients with olfactory dysfunction had fever compared to those without and this was a significant finding in our study population. The overall median recovery time in our study was 7 days. Prevalence of olfactory dysfunction in our population is in keeping with European studies and most patients recover their sense of smell within a week.


Adapting routines in schools when facing challenging situations: Extending previous theories on routines by considering theories on self-regulated and collectively regulated learning.
Routines play a major role in educational change in schools. But what happens if the routines performed by school staff fail to deal successfully with current challenges? What strategies aid adaptation of the routines in a specific situation? Up to now, there exists no comprehensive concept for understanding why and at what points the adapting of routines in schools in a specific situation takes a favorable or unfavorable direction. To address this gap, we propose extending theories on routines by considering theories on self-regulated and collectively regulated learning. We consider these theories to be a beneficial complement because of their broad theoretical, methodological, and empirical research base. We argue that these theories enhance the understanding of adapting routines to specific challenging situations in schools. We present a newly developed theoretical framework for dealing with specific challenging situations in schools as an interplay between routines and regulation processes. Finally, important research questions regarding the suggested approach are discussed.


[Anxiety and depression in headache patients. The example of managed care of chronic headache patients in Bavaria].
The prevalence of anxiety and depression and the influence of headache severity on these illnesses were examined in patients who were part of the managed care of headache in Bavaria. A total of 181 patients with headache were screened for anxiety and depression with the German version of the Hospital Anxiety and Depression Scale (HADS-D). Headache severity was evaluated using the Migraine Disability Assessment Questionnaire (MIDAS). Apart from purely descriptive evaluations, Spearman's coefficients of correlation were calculated. Of the patients 22.7% and 44.7% obtained results at or above the limit of the normal range of depression and anxiety, respectively and 19.3% had results at or above the limit of the normal range for both illnesses. There were significant coefficients of correlation between the severity of headache and both anxiety and depression. The results confirm the necessity for an interdisciplinary procedure in treating headache patients in order to achieve a successful therapy. Such a treatment can be realised with the concept of managed care.


Role of junctional adhesion molecule-like protein in mediating monocyte transendothelial migration.
Monocyte migration across the vascular endothelium of blood vessels is a key early event in atherosclerosis. The mechanisms underlying monocyte transendothelial migration (TEM), however, are still not completely understood. Here we studied the role of junctional adhesion molecule-like protein (JAML) in regulating monocyte TEM. Firstly, by Western blot and flow cytometry, we showed that JAML was strongly expressed in monocytes and monocyte surface expression of JAML was upregulated by monocyte chemotaxis protein-1 stimulation. Both monocyte adhesion to and migration across tumor necrosis factor-alpha (TNFalpha) preactivated human microvascular endothelial cell (HMEC-1) monolayers were dose-dependently reduced by anti-JAML antiserum or soluble extracellular JAML recombinant. Secondly, short-term exposure of human monocytes and THP-1 cells to advanced glycation end products increased cell surface JAML expression, which was correlated with enhanced cell adhesion and TEM. In contrast, knockdown of JAML in THP-1 monocytes decreased both adhesion and transmigration of THP-1 monocytes. Finally, direct binding assay of the soluble JAML to HMEC-1 monolayers suggested that endothelial coxsackie and adenovirus receptor (CAR) may serve as one of the ligands for JAML. Monocytic JAML plays a critical role in regulating monocyte TEM probably via binding to the endothelial CAR and other tight junction-associated adhesive molecules.


Ecological niche differentiation among six annual Lythrum species in Mediterranean temporary pools.
The ecological niche defines the favourable range of a species in a multidimensional space of ecological factors that determine the presence and function of individuals. This fundamental concept in ecology is widely used to understand plant species coexistence and segregation. In this study, we test for ecological differentiation among six annual Lythrum species that are characteristic of temporary pools in the South of France, where they either coexist or occur separately. We first analysed the co-occurrence of species at two different geographical scales: cluster analyses of species presence in 10 km grid cells and coexistence in 0.25 m2 quadrats within populations of each species. Second, for three to nine populations of each species, we quantified a range of biotic and abiotic parameters using point contacts and soil measurements in five 0.25 m2 quadrats per population. We performed PCA on all variables and analysed each variable separately to compare the ecological niche features of the six species. A phenological index was assessed for the plant community of each site. We detected highly localized niche differentiation in terms of soil pH (all species) and for a range of variables among pairs of species. The six species also showed marked differences in the flowering period relative to the mean and variability of flowering time in their local community. These fine-scaled niche differences are associated with phylogenetic distances among species and may contribute to species' coexistence. These results are integrated in a conservation management plan for the habitat of the rarest species in this group.


Pregnancy-associated mortality after birth, spontaneous abortion, or induced abortion in Finland, 1987-2000.
To test the hypothesis that pregnant and recently pregnant women enjoy a "healthy pregnant women effect," we compared the all natural cause mortality rates for women who were pregnant or within 1 year of pregnancy termination with all other women of reproductive age. This is a population-based, retrospective cohort study from Finland for a 14-year period, 1987 to 2000. Information on all deaths of women aged 15 to 49 years in Finland (n=15,823) was received from the Cause-of-Death Register and linked to the Medical Birth Register (n=865,988 live births and stillbirths), the Register on Induced Abortions (n=156,789 induced abortions), and the Hospital Discharge Register (n=118,490 spontaneous abortions) to identify pregnancy-associated deaths (n=419). The age-adjusted mortality rate for women during pregnancy and within 1 year of pregnancy termination was 36.7 deaths per 100,000 pregnancies, which was significantly lower than the mortality rate among nonpregnant women, 57.0 per 100,000 person-years (relative risk [RR] 0.64, 95% CI 0.58-0.71). The mortality was lower after a birth (28.2/100,000) than after a spontaneous (51.9/100,000) or induced abortion (83.1/100,000). We observed a significant increase in the risk of death from cerebrovascular diseases after delivery among women aged 15 to 24 years (RR 4.08, 95% CI 1.58-10.55). Our study supports the healthy pregnant woman effect for all pregnancies, including those not ending in births.


Paddy crop yield estimation in Kashmir Himalayan rice bowl using remote sensing and simulation model.
The Kashmir Himalayan region of India is expected to be highly prone to the change in agricultural land use because of its geo-ecological fragility, strategic location vis-à-vis the Himalayan landscape, its trans-boundary river basins, and inherent socio-economic instabilities. Food security and sustainability of the region are thus greatly challenged by these impacts. The effect of future climate change, increased competition for land and water, labor from non-agricultural sectors, and increasing population adds to this complex problem. In current study, paddy rice yield at regional level was estimated using GIS-based environment policy integrated climate (GEPIC) model. The general approach of current study involved combining regional level crop database, regional soil data base, farm management data, and climatic data outputs with GEPIC model. The simulated yield showed that estimated production to be 4305.55 kg/ha (43.05 q h(-1)). The crop varieties like Jhelum, K-39, Chenab, China 1039, China-1007, and Shalimar rice-1 grown in plains recorded average yield of 4783.3 kg/ha (47.83 q ha(-1)). Meanwhile, high altitude areas with varieties like Kohsaar, K-78 (Barkat), and K-332 recorded yield of 4102.2 kg/ha (41.02 q ha(-1)). The observed and simulated yield showed a good match with R (2) = 0.95, RMSE = 132.24 kg/ha, respectively.


Recent Developments of Carbon Dots in Biosensing: A Review.
Early diagnosis of diseases is of great importance because it increases the chance of a cure and significantly reduces treatment costs. Thus, development of rapid, sensitive, and reliable biosensing techniques is essential for the benefits of human life and health. As such, various nanomaterials have been explored to improve performance of biosensors, among which, carbon dots (CDs) have received enormous attention due to their excellent performance. In this Review, the recent advancements of CD-based biosensors have been carefully summarized. First, biosensors are classified according to their sensing strategies, and the role of CDs in these sensors is elaborated in detail. Next, several typical CD-based biosensors (including CD-only, enzymatic, antigen-antibody, and nucleic acid biosensors) and their applications are fully discussed. Last, advantages, challenges, and perspectives on the future trends of CD-based biosensors are highlighted.


Fetal growth and Doppler assessment in patients with a history of bilateral internal iliac artery embolization.
Pregnancy occurring after pelvic arterial embolization for postpartum hemorrhage is rare. The harmlessness of this procedure for subsequent pregnancies is poorly documented. Eight pregnant women with a history of arterial embolization were followed up with fetal growth and Doppler assessment. Fetal growth and umbilical Doppler findings remained normal in all cases. Embolization, a life-saving and fertility-preserving procedure, does not seem to affect subsequent pregnancies.


Awaking effect of prostaglandin E2 in freely moving rats.
The awaking effect of prostaglandin (PG) E2 was further examined in a long-term bioassay system. PGE2 in saline solution was infused between 11.00 and 17.00 h at 0.1, 1, 10, and 100 pmol/min (infusion volume 10 microliters/h) into the third cerebral ventricle of freely moving rats. These rats were otherwise infused with saline continuously and exhibited a circadian cycle, spending 70% of the daytime and 37% of the night in sleep. In the rats that received PGE2 infusion at 1, 10, and 100 pmol/min, slow wave sleep (SWS) decreased to 84%, 69% and 71% and paradoxical sleep (PS) to 85%, 37% and 40% of the paired controls. Thus, the effect of PGE2 was not specific to either SWS or PS. No effects were observed in the rats that received PGE2 at 0.1 pmol/min. After PGE2 infusion at 10 and 100 pmol/min, marked rebounds of both SWS and PS occurred during the night. SWS reduction by PGE2 was due to the shortened duration of SWS episodes, while SWS increase in the rebound phase was due to the increased number of episodes. PS reduction was due to both the shortened duration and decreased number of PS episodes and PS rebound was due to both the prolonged duration and increased number of episodes. The circadian sleep-wake cycle returned to the baseline on the first or second recovery day after PGE2 infusion. Sleep reduction by PGE2 was accompanied by elevation of the brain temperature and rebound increase of sleep occurred with the fall of the brain temperature.(ABSTRACT TRUNCATED AT 250 WORDS)


Interleukin (IL)-33: an orchestrator of immunity from host defence to tissue homeostasis.
Interleukin (IL)-33, a member of the IL-1 superfamily, functions as an alarm signal, which is released upon cell injury or tissue damage to alert the immune system. It has emerged as a chief orchestrator in immunity and has a broad pleiotropic action that influences differentiation, maintenance and function of various immune cell types via the ST2 receptor. Although it has been strongly associated with immunopathology, critically, IL-33 is involved in host defence, tissue repair and homeostasis. In this review, we provide an overview of the signalling pathway of IL-33 and highlight its regulatory functions in immune cells. Furthermore, we attempt a broader discussion of the emerging functions of IL-33 in host defence, tissue repair, metabolism, inflammatory disease and cancer, suggesting potential avenues to manoeuvre IL-33/ST2 signalling as treatment options.


How to rule the nucleus: divide et impera.
Genome-wide molecular studies have provided new insights into the organization of nuclear chromatin by revealing the presence of chromatin domains of differing transcriptional activity, frequency of cis-interactions, proximity to scaffolding structures and replication timing. These studies have not only brought our understanding of genome function to a new level, but also offered functional insight for many phenomena observed in microscopic studies. In this review, we discuss the major principles of nuclear organization based on the spatial segregation of euchromatin and heterochromatin, as well as the dynamic genome rearrangements occurring during cell differentiation and development. We hope to unite the existing molecular and microscopic data on genome organization to get a holistic view of the nucleus, and propose a model, in which repeat repertoire together with scaffolding structures blueprint the functional nuclear architecture.


Inflammatory bowel disease and asthma: a population-based, case-control study.
A few cross-sectional studies reported an increased risk of inflammatory bowel disease (IBD) among asthmatics. We conducted a population-based, case-control study that applied predetermined criteria for asthma and IBD to determine whether asthma, as a T-helper 2 (Th2) condition, reduces the risk of IBD, a Th1 condition. This was a population-based, case-control study using criteria-based ascertainment for IBD and asthma. Subjects were all Rochester, Minnesota, residents who had developed IBD between 1964 and 1983 and their age- and gender-matched controls, using 1:1 matching. Controls were randomly selected from the community using the Rochester Epidemiology Project database and confirmed not to have IBD. All cases and controls were merged with the database comprising all Rochester residents with or without asthma between 1964 and 1983. Of the 231 IBD cases, 55% had ulcerative colitis and the remainder had Crohn's disease. Of these, 50.4% were male and 98.1% were Caucasians. The mean age at the time of IBD diagnosis was 33.8 years. Four cases (1.7%) had asthma prior to the index date of IBD, whereas two controls (0.9%) had asthma (unadjusted odds ratio [OR]: 3.0, 95% confidence interval [CI]: 0.31-28.84, P = 0.34). Similarly, 16 IBD cases (6.9%) had asthma ever while 12 controls (5.2%) had asthma ever (unadjusted OR: 1.4, 95% CI: 0.62-3.38, P = 0.40). Asthma as a Th2 condition does not reduce the risk of IBD as a Th1 condition. Because of the limitations of our study and others, the association between asthma and IBD needs to be further studied.


In-hospital outcomes and conditions in patients with acute coronary syndrome and coronary artery aneurysms who undergo percutaneous coronary intervention.
Coronary artery aneurysms (CAA) are uncommon, often incidental findings in patients with acute coronary syndrome (ACS) that represent a management challenge due to as there is a paucity of literature in this area. We analyzed the National Inpatient Sample database from 2016 to 2020 by including all patients with the admission diagnosis of the ACS who underwent percutaneous coronary intervention (PCI). We sought to evaluate the association of CAA with other relevant systemic conditions and determine the impact of CAA on in-hospital outcomes. Among 1,733,655 hospital admission with ACS who underwent PCI, 2675 had CAA. There was a 2-fold increase in odds of CAA if the patient had coronary artery dissection (OR 2.05 95%CI 1.12-3.75, p = 0.020) or extracoronary aneurysm (OR 2.47 95%CI 1.46-4.16, p = 0.001) and a 3-fold increase in odds if they had a systematic inflammatory disorder (OR 3.24 95%CI 2.08-5.07, p < 0.001). CAA was not associated with increased odds of mortality (OR 1.22 95%CI 0.76-1.95, p = 0.42), bleeding (OR 1.29 95%CI 0.86-1.95, p = 0.22), acute stroke (OR 0.91 95%CI 0.40-2.07, p = 0.83), major adverse cardiac and cerebrovascular events (OR 1.08 95%CI 0.72-1.61, p = 0.71) or cardiac complications (OR 0.85 95%CI 0.49-1.47, p = 0.55). However, it was significantly associated with increased odds of vascular complications (OR 2.17 95%CI 1.47-3.19, p < 0.001). For patients with ACS who undergo PCI, the presence of CAA is associated with greater odds of vascular complications but after adjustments there was no difference in mortality or other complications. In this population, CAA is more prevalent in patients with coronary dissection, extracoronary aneurysms and systemic inflammatory disorders.


Characterization and identification of the glucose transporter of human erythrocytes.
The glucose transporter was purified from human erythrocytes (Kasahara, M. and Hinkle, P.C. (1977) J. Biol. Chem. 252, 7384-7390). The following results support the conclusion that a major protein in the purified transporter fraction, zone 4.5 is the glucose transporter (or a part of the transporter) and is different from band 3: (1) peptide maps of zone 4.5 were similar throughout the broad band in sodium dodecyl sulfate-gel electrophoresis and were different from those of band 3, (2) specific binding of cytochalasin B was found to the transporter fraction, but not to a band 3 fraction, (3) the N-terminal amino acid analysis of the transporter fraction showed a single N-terminal of lysine, whereas the band 3 fraction showed no clear N-terminal, and (4) the rabbit antibody raised against the transporter fraction formed a precipitation line with the transporter fraction, but not with the band 3 fraction. A filtration apparatus was devised for quick and accurate measurement of cytochalasin B binding, with which results comparable to those from equilibrium dialysis were obtained.


Synthesis of superparamagnetic Fe3O4/PMMA/SiO2 nanorattles with periodic mesoporous shell for lysozyme adsorption.
A new kind of nanorattle, composed of a Fe(3)O(4)/polymethyl methacrylate (PMMA) composite nanospherical core and mesoporous SiO(2) shell, has been successfully synthesized with the combination of a modified stöber method and a dual-template strategy, followed by alcohol dialysis. The nanorattles showed high efficiency in protein adsorption and separation.


Serum proteomic identification and validation of two novel atherosclerotic aortic aneurysm biomarkers, profilin 1 and complement factor D.
Effective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis. We performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated. Profilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study. PFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.


Specific Varicella-Related Complications and Their Decrease in Hospitalized Children after the Introduction of General Varicella Vaccination: Results from a Multicenter Pediatric Hospital Surveillance Study in Bavaria (Germany).
Universal varicella vaccination (UVV) for children introduced in Germany in 2004 resulted in a significant overall decline of varicella-related hospitalizations (VRHs). We investigated the incidence of specific types of varicella-related complications (VRCs) in hospitalized children and the impact of UVV on VRCs during the first 7 years of UVV. Children < 17 years of age hospitalized with an ICD-10-based (International Classification of Diseases, 10th Revision) discharge diagnosis of varicella were identified as VRH in pediatric hospitals in Bavaria by annual standardized data queries of the hospital databases (2005-2011). For each VRH, the hospitals reported basic demographic data, duration of hospital stay, all diagnostic and procedural codes, and outcome. VRCs were reported overall, per year, and by immune status. Complication rates were calculated as mean number per complication category per hospital and per year; VRC trends over time were assessed by linear regression. Between 78% (2005) and 61% (2011) of Bavarian hospitals participated and reported a total of 1263 VRHs. Specific VRCs were reported in 954 (76%) children. Complication rates per hospital and year decreased from 6.7 [95% confidence interval (CI): 5.1-8.3] in 2005 to 1.5 (95% CI: 0.8-2.3) in 2011, with the strongest reduction of 90% in children < 5 years of age from 5.3 (95% CI: 4.0-6.6) in 2005 to 0.5 (95% CI: 0.1-0.9) in 2011. Significant decreases were observed for children with upper respiratory tract (URT, by 97%), lower respiratory tract (LRT, by 90%), skin (by 81%), gastrointestinal (by 78%), and neurologic (by 65%) VRCs. Forty-eight children with VRCs were immunocompromised; their annual rate decreased by 87%. Corresponding to increasing varicella vaccination coverage in the population, the incidence of VRC decreased by 77% from 2005 to 2011, with the most substantial decrease in the target group for UVV. Within 7 years, UVV in Germany led to a decrease of about 77% of all types of VRCs, with the highest reductions observed for VRCs of the respiratory tract.


Isolation and separation of alpha and beta-tubulin from chick-embryo brain, muscle and skin.
Two kinds of tubulin, alpha and beta, have been described in microtubules from many different systems. In the present study a new method is described for isolating and separating these two kinds of tubulin from chick-embryo brain, muscle and skin. The isolated tubulins were characterized by polyacrylamide-gel disc electrophoresis in the presence of urea and sodium dodecyl sulphate.


Pituitary apoplexy masquerading as meningoencephalitis.
Pituitary apoplexy, a rare but life-threatening disorder, is characterized by the abrupt destruction of pituitary tissue secondary to infarction or hemorrhage of the gland itself. Its clinical features include severe headache, stiff neck, fever, visual disturbances, and symptoms of hypoadrenalism. To assess how pituitary apoplexy may mimic the clinical findings of an infectious meningoencephalitis. We describe 3 individuals whose clinical profile and paraclinical studies were consistent with a diagnosis of presumed infectious meningoencephalitis. With minimal improvement on antimicrobial therapy, however, an extensive clinical and radiographic reevaluation yielded pituitary apoplexy as the etiology of their acute neurologic event. Pituitary apoplexy is often misdiagnosed as meningitis or subarachnoid hemorrhage due to the presence of leukocytes and erythrocytes in the cerebrospinal fluid. These cases serve to highlight the importance of maintaining a broad differential diagnosis when evaluating patients presenting with an acute headache.


Long-term results of office-based pneumatic retinopexy using pure air.
The long-term results of office-based pneumatic retinopexy (PR) using only filtered air were evaluated in a case series of rhegmatogenous retinal detachments with more than 3 years of follow-up, on average. 77 cases of primary rhegmatogenous retinal detachments arising from superior tears (mean=1.6 tears) were treated with cryopexy (n=61) or laser (next day, n=16) and intravitreal injection of pure air in an office setting. The macula was detached preoperatively in 37 eyes (48.1%). Outcome measures were single-operation success, final reattachment rates and visual acuity (VA). Subjects were followed for 6-186 months (mean follow-up = 40.7 months, 46.8% ≥ 2 years, 25% ≥ 5 years). In all cases, the air bubble was gone within 5 days. Single-operation success was achieved in 62/77 (80.5%) eyes. Repeat PR was successful in four cases, increasing the PR reattachment rate to 85.7%. Scleral buckle was performed on the remaining 11 eyes (14.3%), 1 with vitrectomy. The final reattachment rate was 100%. VA improved ≥ 2 Snellen lines in 53.2% of patients, with 50/77 (64.9%) attaining VA ≥ 20/40. Following PR, 87% of subjects had the same or better VA. Office-based pure-air PR achieves acceptable reattachment rates with good visual outcomes and long-term efficacy. Eliminating the need for expansile gases makes this approach more widely available, decreases recovery time and lowers healthcare costs.


Cutaneous Angiosarcoma: Clinical and Pathology Study of 16 Cases.
Primary cutaneous angiosarcoma is one of the most aggressive skin tumors and carries a very poor prognosis. Its initially indolent clinical presentation explains the frequently late diagnosis that, together with its typically multifocal pattern and poor delimitation, often makes surgery difficult. The low incidence of primary cutaneous angiosarcoma means that few large single-center series have been published. We review the clinical and pathologic characteristics of cutaneous angiosarcomas treated in our hospital, looking for prognostic factors and for possible diagnostic traits that could facilitate early diagnosis. This was a retrospective observational study including all patients diagnosed with cutaneous angiosarcoma in Instituto Valenciano de Oncología in Valencia, Spain between January 2000 and December 2015. We recorded 16 clinical parameters, including age, sex, type of angiosarcoma, site, size, and time since diagnosis, and 8 histopathologic parameters. We identified 16 patients (11 women and 5 men) with cutaneous angiosarcoma. Their mean age was 67 years (median, 71 years). The most common site was the trunk (10 cases), followed by the head and neck (5 cases). The mean size of the tumor was 10cm (median, 6.5cm). Fourteen patients underwent surgical excision. Six of the 16 patients were alive at the end of the study, after a mean follow-up period of 42.5 months. The major determinants of survival among patients with cutaneous angiosarcoma are tumor size and patient age. Other characteristics associated with a poor prognosis were infiltration of deep planes (muscle), a predominantly solid histologic pattern, and a larger number of mitoses.


The Role of Preschool Dosage and Quality in Children's Self-Regulation Development.
The present study examined how the dosage and quality of the federal preschool program "Head Start" (HS) in the US related to children's self-regulation skills in kindergarten. Using Propensity Score Matching and multiple regression (OLS), this study explored how the number of years and hours a week of HS were related to self-regulation among 2,383 children, who entered the program either at 3 or 4 years old. An additional year in HS was significantly positively associated with self-regulation in kindergarten, while the number of hours a week in HS was not. However, the quality of teacher-child interactions moderated the relation between hours a week in HS and self-regulation. Findings contribute to the growing body of evidence about how dosage and quality of early childhood education experiences relate to children's development.


Survival by age in paediatric and adolescent patients with Hodgkin lymphoma: a retrospective pooled analysis of children's oncology group trials.
Adolescents with Hodgkin lymphoma have worse disease outcomes than children. Whether these differences persist within clinical trials is unknown. We examined survival, by age, in patients receiving response-adapted therapy for Hodgkin lymphoma on Children's Oncology Group (COG) trials. Patients (aged 1-21 years) diagnosed with classical Hodgkin lymphoma and enrolled between Sept 23, 2002, and Jan 19, 2012, on one of three phase 3 COG trials in the USA and Canada were eligible for inclusion. The three COG trials were defined by risk group according to Ann Arbor stage, B-symptoms, and bulk (AHOD0431 [low risk; NCT00302003], AHOD0031 [intermediate risk; NCT00025259], or AHOD0831 [high risk; NCT01026220]). The outcomes of this study were event-free survival (death, relapse, or subsequent neoplasm) and overall survival. Cox proportional hazards models estimated survival, adjusting for disease and treatment factors both overall and in patients with mixed cellularity or non-mixed cellularity (nodular sclerosing and not-otherwise-specified) disease. Of 2155 patients enrolled on the three trials, 1907 (88·4%; 968 [50·8%] male and 939 [49·2%] female; 1227 [64·3%] non-Hispanic White) were included in this analysis. After a median follow-up of 7·4 years (IQR 4·3-10·2), older patients (aged ≥15 years) had worse unadjusted 5-year event-free survival (80% [95% CI 78-83]) than did younger patients (aged <15 years; 86% [83-88]; HR 1·38 [1·11-1·71]; p=0·0038). Older patients also had worse unadjusted 5-year overall survival than did younger patients (96% [95% CI 95-97] vs 99% [98-99]; HR 2·50 [1·41-4·45]; p=0·0012). In patients with non-mixed cellularity histology, older patients had a significantly increased risk of having an event than did younger patients with the same histology (HR 1·32 [1·03-1·68]; p=0·027). Older patients with mixed cellularity had significantly worse 5-year event-free survival than did younger patients in unadjusted (77% [95% CI 65-86] for older patients vs 94% [88-97] for younger patients; HR 2·93 [1·37-6·29]; p=0·0039) and multivariable models (HR 3·72 [1·56-8·91]; p=0·0032). Overall, older patients were more likely to die than younger patients (HR 3·08 [1·49-6·39]; p=0·0025). Adolescents (≥15 years) treated on COG Hodgkin lymphoma trials had worse event-free survival and increased risk of death compared with children (<15 years). Our findings highlight the need for prospective studies to examine tumour and host biology, and to test novel therapies across the age spectrum. National Institutes of Health, St Baldrick's Foundation, and Lymphoma Research Foundation.


Comparison of oncology nurse and physician use of the Internet for continuing education.
In the past 10 years, there has been a dramatic increase in published literature on the topic of Internet use by healthcare professionals. Learners and organizations providing grants to the continuing education (CE) division of a medical education and publishing company have expressed increasing interest in the area of Internet CE. To quantify and analyze this trend, the company began using surveys to evaluate this growing area of interest. Since 1998, annual surveys at the annual meetings of the Oncology Nursing Society and the American Society of Clinical Oncology were used to determine trends in educational use of the Internet for CE. Internet use and frequency of use, including use of the Internet for CE among both nurses and physicians, have been increasing. When asked what would make these professionals more likely to use the Internet for CE, both indicated making the activities low cost or free and easier access. Nurses and physicians are looking to the Internet for quick access to reliable information, thus challenging CE educators to develop ways to implement Internet CE activities quickly. Ongoing needs assessment of target audiences and evaluation of the effectiveness of Internet CE is essential to optimizing the role of this educational format for healthcare professionals.


Functional assay of the mutant tissue-nonspecific alkaline phosphatase gene using U2OS osteoblast-like cells.
Tissue-nonspecific alkaline phosphatase (TNAP) plays a key role in mineralization. A defect in the TNAP gene causes hypophosphatasia, which is characteristic of systemic skeletal hypomineralization. To determine the mineralizing ability of the mutant proteins, we developed a functional assay that uses U2OS osteoblast-like cells. Expression plasmids containing TNAP mutant cDNAs were constructed and introduced into U2OS cells, which are derived from a human osteosarcoma and exhibit very low alkaline phosphatase (ALP) activity and disabled mineralization. U2OS cells, in which active TNAP cDNAs were introduced, expressed high ALP activity and mineralized their circumstance when they were cultured with beta-glycerophosphate. The ALP activity in these U2OS cells corresponded to the activity reported for COS cells in which active TNAP cDNA was introduced. An in vitro mineralization assay of U2OS cells transfected with moderate allele cDNAs showed that approximately 35% of TNAP enzymatic activity may be the threshold value for mineralization. In addition, U2OS cells transfected with wild-type TNAP and polymorphism TNAP cDNA showed PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) induction as in SaOS-2 cells. In summary, the introduction of active TNAP cDNA into U2OS cells allowed these cells to mineralize, and this technique may be a useful functional assay of TNAP mutant proteins.


Rape of girls in South Africa.
Child rape violates human rights and causes immediate and long-term health problems for the child. In the 1998 South Africa Demographic and Health Survey, we assessed frequency of rape in a nationally representative study of 11735 women aged 15-49 years. 153 (1.6%, 95% CI 1.2-1.9%) of these women had been raped (forced or persuaded to have sex against their will) before the age of 15 years. Our results show that younger women were significantly more likely to report rape than older women (p<0.0001). The largest group of perpetrators (33%) were school teachers. Our findings suggest that child rape is becoming more common, and lend support to qualitative research of sexual harassment of female students in schools in Africa.


Measuring traction forces of motile dendritic cells on micropost arrays.
Dendritic cells (DCs) migrate from sites of inflammation to secondary lymphoid organs where they initiate the adaptive immune response. Although motility is essential to DC function, the mechanisms by which they migrate are not fully understood. We incorporated micropost array detectors into a microfluidic gradient generator to develop what we consider to be a novel method for probing low magnitude traction forces during directional migration. We found migration of primary murine DCs is driven by short-lived traction stresses at the leading edge or filopodia. The traction forces generated by DCs are smaller in magnitude than found in neutrophils, and of similar magnitude during chemotaxis and chemokinesis, at 18 ± 1.4 and 16 ± 1.3 nN/cell, respectively. The characteristic duration of local DC traction forces was 3 min. The maximum principal stress in the cell occurred in the plane perpendicular to the axis of motion, forward of the centroid. We illustrate that the spatiotemporal pattern of traction stresses can be used to predict the direction of future DC motion. Overall, DCs show a mode of migration distinct from both mesenchymal cells and neutrophils, characterized by rapid turnover of traction forces in leading filopodia.


Patient-perceived pain during laser in situ keratomileusis: comparison of fellow eyes.
To compare pain scores during laser in situ keratomileusis (LASIK) between first-eye surgery and second-eye surgery. Private practice, Beirut, Lebanon. Cohort study. Sequential bilateral LASIK was performed between January 2010 and January 2011 by the same surgeon using a Schwind Amaris excimer laser. Hemodynamics and intraocular pressure (IOP) were monitored intraoperatively. Patients graded their pain perception on a 4-point scale after the completion of each eye's surgery. The study enrolled 154 patients. The first surgery was performed in the right eye in 106 patients and in the left eye in 48 patients. Patients reported discomfort during suction (mean pain score 0.80 ± 0.56 [SD]). More pain was reported during second-eye surgery by 74% of patients; 2% reported more pain in the first eye, and 24% reported equal pain in both eyes. The mean pain score was 0.63 ± 0.35 in the first eye and 0.93 ± 0.51 in the second eye (P=.01). Pain was higher during second-eye surgery whether the procedure was started in the right eye or in the left eye. Systolic blood pressure was also higher during second-eye surgery (P=.001). There was no statistically significant difference in diastolic blood pressure, heart rate, IOP, or suction-ring pressure. Patients had more pain during second-eye LASIK for reasons that are not clear. A psychological explanation or regional sensitization processes are potential factors and should be studied. No author has a financial or proprietary interest in any material or method mentioned.


Diagnostic fundus autofluorescence patterns in achromatopsia.
To describe the unique diagnostic fundus autofluorescence (FAF) patterns in patients with achromatopsia and the associated findings on optical coherence tomography (OCT). Observational case series. We evaluated 10 patients with achromatopsia by means of best-corrected visual acuity (BCVA), ophthalmoscopy, Goldmann visual field, full-field electroretinography (ffERG), OCT, and FAF photography. FAF patterns were compared with patient age and foveal changes on OCT. Patients fell into two dichotomous age groups at the time of evaluation: six patients ranged from 11 to 23 years of age, and 3 patients ranged from 52 to 63 years of age. All patients had severely reduced photopic ffERG responses, including those exhibiting preserved foveal structure on OCT. The younger patients had absent to mild foveal atrophy on OCT, and four of the six demonstrated foveal and parafoveal hyperfluorescence on FAF. In addition, a 7-month-old child with compound heterozygous mutations in CNGA3 demonstrated similar foveal hyperfluorescence. The older patients demonstrated advanced foveal atrophy and punched-out foveal hypofluorescence with discrete borders on FAF imaging corresponding to the area of outer retinal cavitation on OCT. Foveal hyperfluorescence is an early sign of achromatopsia that can aid in clinical diagnosis. In our cohort, patients with achromatopsia demonstrated age-dependent changes in FAF, which are likely to be progressive and to correlate with foveal atrophy and cavitation on OCT. This finding may be useful in charting the natural course of the disease and in defining a therapeutic window for treatment.


Functional imaging of stress urinary incontinence.
Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during increases in intraabdominal pressure such as coughing or laughing. It is often a consequence of weakness of the pelvic floor. Treatment of SUI consists of pelvic floor muscle training with EMG-biofeedback (PFMT) or contraction-exercises, with voluntary pelvic contractions in order to strengthen the pelvic floor. We investigated neuroplastic changes comparing PFMT with EMG-biofeedback before and after training in ten female patients with SUI using event-related functional Magnetic Resonance Imaging (fMRI). After a 12-week training a more focused activation in the primary motor and somatosensory cortical representation sites of the lower urogenital tract was found. In addition, reductions in brain activation in the insula, right frontal operculum and the anterior cingulate cortex suggest changes in emotional arousal in micturition after treatment. These changes are related to clinical improvement documented by decreased number of incontinence episodes and increased EMG-activity of the pelvic floor muscles after training. The changes in EMG-activity were correlated with heightened BOLD responses in the primary motor and primary sensory cortical representation sites of the lower urogenital tract.


A single administration of tetanus toxoid in biodegradable microspheres elicits T cell and antibody responses similar or superior to those obtained with aluminum hydroxide.
The use of biodegradable polymer microspheres as a single dose vaccine delivery system was investigated by using tetanus toxoid (TT). In order to compare the immunogenicity of TT-microspheres (TT-MS) with aluminum hydroxide (alum)-based TT, BALB/c mice were immunized with TT in different formulations including individual or mixtures of MS and TT-alum. All TT-MS formulations elicited high proliferative and antibody responses comparable to those obtained with TT-alum formulation. Antibody levels remained elevated over a long period of time. Certain individual MS preparations elicited lower antibody titers than the MS mixtures. More importantly, the proliferative and antibody responses induced by a single injection of three TT-MS mixtures with different particle sizes and degradation rates were similar to those obtained with three injections of TT-alum. In addition, TT-MS induce similar isotypesubclass antibodies to those TT-alum induced. These results raise the possibility to obtain optimal and long-lasting immune responses by single administration of the three TT-MS mixture formulations alone.


[Aggressive mediastinal fibrosis, a rare cause of superior vena cava obstruction--case report and review of the literature].
An aggressive mediastinal fibrosis was found to be a cause of superior vena caval obstruction in 1 to 2% of patients. Symptoms can be discrete for a long time, but the progressing disease can cause many symptoms. A 56-year-old man who, for half a year, suffered from thoracic pain during deep inspiration, and then rapidly developed superior vena caval obstruction caused by aggressive mediastinal fibrosis is discussed. The operative treatment consisted in complete replacement of the superior vena cava.


A mechanical model for the human intervertebral disc.
Stress relaxation experiments were performed on specimens from a human intervertebral disc. Specimens were made from the nucleus pulposus and from the external lamellae of the anulus fibrosus in two different orientations. Tests were run with varying moisture content so as to develop a relaxation master curve. A model was developed based on the experimental data. It was found that the short term master curve for the lamellae of the anulus and nucleus are similar, whereas the long term rubbery plateau is different between the lamellae and the nucleus. It was also established that the master curves for different lamellae and the nucleus were shifted relative to each other in the time domain due to changes in water content. The average relaxation modulus of the whole disc was obtained by averaging the properties between the anulus and nucleus. This model was then used for studies of Schmorl's nodes, of degenerated discs and for circumstances in which hydration is considered to be important.


Endoscopic Stent Placement Can Successfully Treat Gastric Leak Following Laparoscopic Sleeve Gastrectomy If and Only If an Esophagoduodenal Megastent Is Used.
Gastric staple line leakage (GL) is a serious complication of laparoscopic sleeve gastrectomy (LSG), with a specific mortality ranging from 0.2 to 3.7%. The current treatment of choice is stent insertion. However, it is unclear whether the type of stent which is inserted affects treatment outcome. Therefore, we aimed not only to determine the effectiveness of stent treatment for GL but also to specifically clarify whether treatment outcome was dependent on the type of stent (small- (SS) or megastent (MS)) which was used. A single-centre retrospective study of 23 consecutive patients was conducted to compare the outcomes of SS (n = 12) and MS (n = 11) for the treatment of GL following LSG. The primary outcome measure was the success rate of stenting, defined as complete healing of the GL without changing the treatment strategy. Treatment change or death were both coded as failure. The success rate of MS was 91% (10/11) compared to only 50% (6/12) for SS (p = 0.006). An average of 2.3 ± 0.5 and 6.8 ± 3.7 endoscopies were required to achieve healing in the MS and SS groups respectively (p < 0.001). The average time to resumption of oral nutrition was shorter in the MS group (1.4 ± 1.1 days vs. 23.1 ± 33.1 days, p = 0.003). Stent therapy is only effective and safe for the treatment of GL after LSG if a MS is used. Treatment with a MS may not only increase treatment success rates but may also facilitate earlier resumption of oral nutrition and shorten the duration of hospitalization.


Continuous tissue pH monitoring in the term fetus.
Since Saling's work in 1961, many investigators have attempted to perfect methods to detect fetal acidosis during labor. A system for continuous tissue pH monitoring of the fetus is evaluated in this study of 59 patients. There was poor correlation of tissue pH values and capillary scalp pH values in 19 cases (r = 0.487), and no significant correlation of tissue pH values to the outcome measurements of Apgar scores and cord gas levels. The benefits realized were those of monitoring the trend of tissue pH over time. We believe that a continuous pH monitoring system offers several advantages over intermittent fetal scalp sampling. Further refinement of the technology employed may offer such a system in the future.


Use of ventricular cerebrospinal fluid lactate measurement to diagnose cerebrospinal fluid infection in patients with intraventricular haemorrhage.
Early diagnosis of ventriculostomy-associated cerebrospinal fluid (CSF) infection in acute neurosurgical patients can be difficult. The use of prophylactic antibiotics in intraventricular or subarachnoid haemorrhage decreases the sensitivity of cell counts, Gram staining and bacterial culture as diagnostic tools. We prospectively collected clinical and cerebrospinal data for 16 patients with intraventricular haemorrhage, with an external ventricular drain inserted, with or without spontaneous subarachnoid haemorrhage. Three (18.8%) patients had cerebrospinal fluid infection, with appropriate changes in antibiotic regimens needed. All three patients had CSF lactate levels of >4 mmol/L (6.4 mmol/L, 7.8 mmol/L, 7.9 mmol/L). Eleven out of 13 patients without CSF infection had CSF lactate levels of below 4 mmol/L. The two patients with CSF lactate levels of 4-6 mmol/L were grade 5 subarachnoid haemorrhage patients, one with renal impairment. Using a cut-off lactate level of 4 mmol/L, the positive predictive value was 60% and negative predictive value was 100% for CSF infection. A CSF lactate level of above 4 mmol/L should prompt suspicion of CSF infection in intraventricular haemorrhage patients with an external ventricular drain.


Two-stage treatment for severe spinal kyphotic deformity secondary to tuberculosis: halo-pelvic traction followed by a posterior-only approach correction.
Several surgical procedures are used to treat tuberculous kyphosis. However, the treatment of extreme spinal kyphosis is challenging, and associated with various complications. Halo traction has been used as an adjunctive method in the treatment of severe spinal deformities. However, there are few reports about the effectiveness of halo-pelvic traction (HPT) for the treatment of extreme spinal kyphosis secondary to tuberculosis. This study evaluated the effectiveness of halo-pelvic traction followed by a posterior-only approach correction in the treatment of severe spinal kyphosis secondary to tuberculosis. The records of 19 patients with severe spinal kyphosis secondary to tuberculosis were retrospectively reviewed. All 19 patients were treated with a two-stage approach: HPT combined with posterior fusion surgery by a posterior-only approach. Radiographic parameters were measured and evaluated. America Spinal Injury Association grade (ASIA), Scoliosis Research Society outcome (SRS-22) score, and complications were also evaluated. There were 9 males and 10 females, with an average age of 29.7 years at the time of surgery. The average HPT duration was 10.4 weeks. The mean kyphosis angle decreased from 131.40 ± 10.7° pre-traction to 77.1 ± 7.4° post-traction (P < 0.01). The traction correction rate was 41.3%. The mean postoperative kyphosis angle was 65.7 ± 8.5°, and the surgical correction rate was 8.7%. Of the total correction, 82.6% was the result of HPT. At a mean follow-up of 26.5 months, the average kyphosis correction loss was 2.9°. The mean sagittal balance was 11.1 ± 45.2 mm before traction, - 25.0 ± 37.4 mm after traction, 7.0 ± 13 mm after surgery, and 2.8 ± 9.6 mm at the final follow-up. The mean preoperative SRS-22 score was 3.0 and postoperative was 4.2 (P < 0.01). The neurological status of most patients was improved. The total complication rate was 15.7%, including 1 neurological and 2 non-neurological complications. HPT is effective in the management of severe spinal kyphotic deformity secondary to tuberculosis. Preoperative HPT can greatly reduce global kyphosis, and the need for corpectomy.


The Value of Etoposide for Recurrent Glioma.
For multiply recurrent glioma, options are few and choices are very limited. Etoposide in combination with carboplatin and/or bevacizumab has been evaluated in recurrent glioma with modest efficacy. This retrospective study describes the efficacy of etoposide monotherapy in adults with multiply recurrent diffuse glioma. In this single center retrospective series, all adult patients with radiographically proven multiply recurrent diffuse glioma (WHO grade 2-4) treated with etoposide between 2016 and 2020 were evaluated. Progression-free survival (PFS) and overall survival (OS) after initiating etoposide were calculated for the total group and for different histologic tumor types. In addition, treatment-related toxicity was recorded. Totally, 48 patients with a median age 43 years-old (range 24-78) were included. Etoposide was given as 3rd line of treatment in 18 patients (37.5%) and as 4th or 5th line of treatment in 30 patients (62.5%). The majority were diagnosed with a glioblastoma, WHO grade 4 (27, 56.3%). The median PFS was 8.6 weeks (95% confidence interval [CI]: 8.3-8.9). The median OS of the total population was 4.0 months (95% CI: 2.4-5.6). Patients with an oligodendroglioma had the best OS (median 13 months), compared to astrocytoma and glioblastoma, but the difference was not statistically significant (p = 0.15). Etoposide was stopped due to progression in the majority of the patients (81.3%). Only 1 patient had a grade 3 toxicity. Etoposide is a well-tolerated chemotherapy in heavily pretreated patients with multiply recurrent glioma and could be considered when other options are not available. OS was 4 months after initiating etoposide.


Experimental and theoretical studies on circularly polarized phosphorescence of a [2.2]paracyclophane-based platinum(ii) complex.
An optically active binuclear platinum(ii) complex based on planar chiral [2.2]paracyclophane was synthesized. The corresponding enantiomers exhibited red circularly polarized phosphorescence (CPP) with the dissymmetry factor |glum| = 1.0 × 10-3. We report, for the first time, theoretical estimation of the CPP |glum| value using relativistic calculations.


The emotional impact of genetic testing and aspects of counseling prior to prescription of oral contraceptives.
Oral contraceptives increase the thrombotic risk in women with factor V Leiden. Emotional aspects of genetic testing prior to the prescription of oral contraceptives (OC), aspects of counseling and referral patterns are widely unknown. Two hundred forty-seven women with and 132 women without factor V Leiden were interviewed by questionnaire. One hundred sixty-one women (65%) with factor V Leiden and 63 (48%) with wild-type factor V responded. One hundred seventy-one women (76%) reported being emotionally disturbed by genetic testing. Eighty percent of women with factor V Leiden and 16% of women with wild-type factor V were discouraged from OC use. Three percent of women with factor V Leiden were encouraged to take OC. Forty-one percent of women with factor V Leiden used at least one hormone contraceptive method after diagnosis. Only 46 women (29%) with factor V Leiden were counseled about the relevance of the mutation in case of pregnancy. Testing for factor V Leiden has considerable emotional impact. Recommendations after testing are not consistently driven by the test result.


[Prevention of cytomegalovirus disease in lung transplantation].
Lung transplant recipients, more than other organ transplant recipients, are at particular risk for cytomegalovirus (CMV) infection and disease. CMV prevention avoids the indirect effects of this virus, such as opportunistic fungal infections and obliterative bronchiolitis, the latter being the major limiting factor in the long-term success of lung-transplantation. CMV prevention strategies have significantly reduced CMV disease and CMV-related mortality. Two major strategies are commonly used for CMV prevention: universal prophylaxis and preemptive therapy. In lung transplant recipients, the efficacy and safety of preemptive treatment have not been studied and therefore, cannot be recommended. Universal prophylaxis is the best strategy for preventing CMV disease in lung transplant recipients. There is no consensus on the optimal duration of prophylaxis, but the recently published GESITRA-SEIMC/REIPI 2011 Guidelines for the management of CMV infection in solid-organ transplant patients recommend 6 months posttransplantation. In D+/R- recipients, this period can be prolonged to 12 months if there are difficulties in monitoring at 6 months posttransplantation. The future of prevention will probably depend on immunoguided strategies.


Analysis of common and emerging brominated flame retardants in house dust using ultrasonic assisted solvent extraction and on-line sample preparation via column switching with liquid chromatography-mass spectrometry.
Brominated flame retardants (BFRs) are persistent and widespread chemicals. Therefore human beings are exposed to BFRs. House dust may be one source of exposure and contains a lot of xenobiotics in relatively high concentrations. In contrast to common GC-MS based methods here an online LC-MS/MS method is presented to quantify 16 BFRs in dust using ultrasonic solvent extraction as a single sample work up step. LOQ from 0.6 (tetrabromobisphenol A) to 80 (polybrominated diphenylethers (BDE 28) ng/g dust were achieved. Data for accuracy, precision and recovery are presented and are comparable to common LC-MS/MS methods in different matrices. In addition 5 real house dust samples were analyzed with high concentration (535 ng/g) for bis(2-ethyl-1-hexyl)tetrabromophthalate which is a novel alternative BFRs to replace common BDE's.


In situ detection of calcium ions with chemically modified microcantilevers.
We report a novel technique of micromechanical detection of trace amounts of calcium ions by using microcantilevers modified with ion-selective self-assembled monolayers (SAMs). The SAM-modified microcantilevers undergo bending due to selective adsorption of calcium ions. Experiments conducted under flow conditions show that the modified cantilevers respond sensitively to calcium ions (Ca(2+)); a Ca(2+) concentration of 10(-9) M can be detected with this technique. Other cations, such as Na(+) and K(+), do not have any effect on the deflection of these cantilevers. We demonstrate two different kinds of SAMs having selectivity for calcium ions.


Primary chromoblastomycosis of the medulla oblongata: complication of heroin addiction.
A 20-year-old male heroin addict had a sudden onset of progressive medullary dysfunction and died within 12 days. Postmortem examination disclosed mycotic granulomas due to primary chromoblastomycosis strictly limited to the medulla oblongata and adjacent leptomeninges. Similar lesions were absent outside the central nervous system. Such pathologic lesions related to narcotic addiction have not been reported previously.


Mediterranean diet and psychological well-being intervention to reverse metabolic syndrome in Chile (CHILEMED trial).
Psychosocial status and lifestyle are key risk factors of non-communicable diseases (NCDs), which, in turn, are main drivers of healthcare costs and morbimortality worldwide, including Chile. Mediterranean diet (MedDiet) is one of the healthiest dietary patterns under study. However, its impact on high-risk conditions, such as metabolic syndrome (MetS), and NCDs outside the Mediterranean Basin remains mostly unexplored. Even though Central Chile has an environment, food production, and culinary traditions comparable to those present in Mediterranean countries, few studies -some with significant methodological limitations- have evaluated the effect of MedDiet on health and/or disease in Chilean subjects. Importantly, a Mediterranean lifestyle is a modus vivendi that integrates physical health with mental and social well-being. Psychological well-being (PWB) is associated with healthy behaviors, positive health outcomes, and longevity, thereby emerging as a novel healthcare goal. We report here an ongoing randomized controlled clinical trial in Chilean patients with MetS seeking to test whether (1) a PWB theory-based intervention facilitates induction to and increases long-term adherence to a locally adapted MedDiet, and (2) a MedDiet intervention -implemented alone or combined with well-being promotion- is more effective at reversing MetS compared to individuals following a low-fat diet without psychological support. The CHILEan MEDiterranean (CHILEMED) diet intervention study is a 1-year trial including patients with MetS living in Chile. Participants will be assigned randomly by a computer-generated random number sequence to one of the three intervention arms: a) low-fat diet as control group, b) MedDiet alone, and c) MedDiet plus well-being support. Patients will be followed-up by individual and/or group online nutritional sessions or phone cal as well as 6- and 12-month in-person re-assessment of medical history, medication use, food intake, PWB, anthropometrics/physical exam, and blood collection for laboratory analysis. The primary outcome of the trial will be the effect of the MedDiet -with or without PWB intervention- on overall reversal of MetS compared to low-fat diet alone. Based on a statistical superiority trial, expected impact, and patient loss, the estimated study sample is 339 subjects (113 individuals per arm in 3 equal-sized groups). Currently, we have enrolled 179 patients, predominantly women, evenly distributed by age (group means ranging from 45.7 to 48,9 years-old), 3/4 are obese with almost all of them showing abdominal obesity, 70% are hypertensive, whereas <10% exhibit diabetes. If findings turn out as expected (e.g., MedDiet -with or without PWB intervention- is better than the low-fat diet for reversion of MetS at 1-year follow-up), CHILEMED will provide further beneficial evidence of the MedDiet on NCD risk conditions beyond the Mediterranean region.


DNA vaccines: a novel approach to immunization.
Direct DNA inoculations are being developed as a method of subunit vaccination. Plasmid DNAs encoding influenza virus hemagglutinin glycoproteins have been tested for the ability to provide protection against lethal influenza challenges. In immunization trials using inoculations of purified DNA in saline, 67-95% of test mice and 25-63% of test chickens were protected against the lethal challenge. Good protection was achieved by intramuscular, intravenous and intradermal injections. In mice, 95% protection was achieved by gene gun delivery of 250-2500 times less DNA than the saline inoculations. Successful DNA vaccination by multiple routes of inoculation and the high efficiency of gene-gun delivery highlight the potential of this promising new approach to immunization.


Diagnosis of pulmonary embolism with CT pulmonary angiography: a systematic review.
To appraise the evidence on the diagnostic accuracy of CT pulmonary angiography and the prognostic value of a negative CT pulmonary angiogram in the diagnosis of pulmonary embolism. Medline, EMBASE, and grey literature were systematically searched by two researchers. Any study which compared CT pulmonary angiography to an acceptable reference standard or prospectively followed up a cohort of patients with a normal CT pulmonary angiogram was included. Study methods were appraised independently by two researchers, and data were extracted independently by three researchers. Thirteen diagnostic and 11 follow up studies were identified. Studies varied in prevalence of pulmonary embolism (19-79%), patient groups, and method quality. Few studies recruited unselected emergency department patients. There was heterogeneity in the analysis of sensitivity (53 to 100%), specificity (79 to 100%), and false negative rate (1.0 to 10.7%). The pooled false negative rate of combined negative CT pulmonary angiography and negative deep vein thrombosis testing was 1.5% (95% CI 1.0 to 1.9%). Diagnostic studies give conflicting results for the diagnostic accuracy of CT pulmonary angiography. Follow up studies show that CT pulmonary angiography can be used in combination with investigation for deep vein thrombosis to exclude pulmonary embolism.


Changes in nuclear receptor corepressor RIP140 do not influence mitochondrial content in the cortex.
Changes in nuclear receptor interacting protein 140 (RIP140) influences mitochondrial content in skeletal muscle; however, the translation of these findings to the brain has not been investigated. The present study examined the impact of overexpressing and ablating RIP140 on mitochondrial content in muscle and the cortex through examining mRNA, mtDNA, and mitochondrial protein content. Our results show that changes in RIP140 expression significantly alters markers of mitochondrial content in skeletal muscle but not the brain.


Long-Term Vault Changes in Different Levels and Factors Affecting Vault Change After Implantation of Implantable Collamer Lens with a Central Hole.
This study evaluated vault changes in eyes implanted with an implantable Collamer lens (ICL) with a central hole (ICL V4c) for myopia and astigmatism correction as well as factors related to vault changes over time. This retrospective study enrolled 169 myopic eyes from 169 patients (137 women and 32 men) who underwent ICL V4c implantation to correct myopia and astigmatism. Vault values were measured quantitatively using a rotating Scheimpflug camera. Each patient underwent at least four postoperative follow-up visits at 1 month, 6 months, 1 year, and more than 2 years. We compared postoperative values between groups and identified factors affecting vault changes over time. The mean vaults at 1 month (baseline), 6 months, 1 year, and the last follow-up time following ICL implantation were 540.83 ± 186.13, 520.00 ± 196.08, 503.79 ± 198.30, and 471.42 ± 211.35 μm, respectively. Eyes with baseline vaults of 250-750 and ≥ 750 μm exhibited a trend of vault decrease over time, and the differences were statistically significant (P < 0.05) at 6 months and 1 year postoperatively, respectively. The variables relevant to the value of vault decrease between baseline and last follow-up time were anterior chamber depth (ACD) and ICL power (adjusted R2 = 0.121, P < 0.001). We found a trend of decreased mean objective vault values over time, which was more obvious in eyes with higher baseline vault values. The vault value of the ICL decreased more in eyes with shallower ACDs, higher ICL power, or both. Moreover, the decrease in vault values became statistically significant earlier in eyes with higher baseline vaults or shallower ACDs.


The genesis of RNA interference, its potential clinical applications, and implications in gynecologic cancer.
This review will discuss the discovery and development of RNA interference (RNAi) technology, small interfering RNA (siRNA) design and delivery, and the implications of RNAi on gynecologic cancers. Systematic review of English language literature using searches for RNAi and gynecologic cancers in established databases, including Pubmed and Ovid, was employed. The high degrees of efficiency and specificity are the main advantages of RNAi. Consequently, RNAi is used in functional genomics and developing therapies for the treatment of viral infection, dominant disorders, neurological disorders, and cancers, including gynecologic cancers. RNAi represents an exciting technology for functional genomics by selective targeting of genes. While issues regarding delivery remain, the therapeutic advantages of siRNA in cancer treatment warrant further investigation.