Responses of distal nephron Na+ transporters to acute volume depletion and hyperkalemia.
We assessed effects of acute volume reductions induced by administration of diuretics in rats. Direct block of Na+ transport produced changes in urinary electrolyte excretion. Adaptations to these effects appeared as alterations in the expression of protein for the distal nephron Na+ transporters NCC and ENaC. Two hours after a single injection of furosemide (6 mg/kg) or hydrochlorothiazide (HCTZ; 30 mg/kg) Na+ and K+ excretion increased but no changes in the content of activated forms of NCC (phosphorylated on residue T53) or ENaC (cleaved γ-subunit) were detected. In contrast, amiloride (0.6 mg/kg) evoked a similar natriuresis that coincided with decreased pT53NCC and increased cleaved γENaC. Alterations in posttranslational membrane protein processing correlated with an increase in plasma K+ of 0.6-0.8 mM. Decreased pT53NCC occurred within 1 h after amiloride injection, whereas changes in γENaC were slower and were blocked by the mineralocorticoid receptor antagonist spironolactone. Increased γENaC cleavage correlated with elevation of the surface expression of the subunit as assessed by in situ biotinylation. Na depletion induced by 2 h of furosemide or HCTZ treatment increases total NCC expression without affecting ENaC protein. However, restriction of Na intake for 10 h (during the day) or 18 h (overnight) increased the abundance of both total NCC and of cleaved α- and γENaC. We conclude that the kidneys respond acutely to hyperkalemic challenges by decreasing the activity of NCC while increasing that of ENaC. They respond to hypovolemia more slowly, increasing Na+ reabsorptive capacities of both of these transporters.


Echocardiographic features of right ventricular infarction.
In a series of 75 consecutive patients with transmural acute myocardial infarction (AMI) a right-to-left ventricular filling pressure ratio equal to or greater than 0.65 (RVFP/LVFP greater than or equal to 0.65) was assumed to be indicative of associated right ventricular infarction (RVI). Out of 45 patients with inferoposterior myocardial infarction, 11 (24%) had such hemodynamic evidence of right ventricular infarction (group A). The remaining 34 patients with inferoposterior myocardial infarction (group B) and the 30 patients with anterior myocardial infarction did not. Time-motion and two-dimensional echocardiographic examinations were performed 7-10 days after admission in the 62 patients who survived. Right ventricular wall asynergy was found in six of eight group A patients. In three of these, right ventricular dilatation was also present. No patient in group B with inferior infarction or with anterior infarction showed abnormal right ventricular wall motion. While hemodynamic monitoring seems presently the most specific diagnostic method and it is of invaluable help in the choice of the best pharmacological therapy of right ventricular failure due to RVI, two-dimensional echocardiography is probably highly sensitive and specific for the diagnosis of RVI, by detecting RV wall motion and thickening abnormalities. Due to advantages, such as noninvasivity and repeatibility, two-dimensional echocardiography can be used in the selection of patients who deserve hemodynamic monitoring and in follow-up studies.


Convulsive thresholds and the activity of anticonvulsants in electroseizure test. The role of serotoninergic system.
The effect of different compounds modifying the activity of serotoninergic system on the convulsive threshold and on anticonvulsant action of phenyltoin (PHEN) phenobarbital (PHB), m-bromophenyl succinimide (BPHSI) and acetazolamide (ACA) in electroseizure test was studied. The obtained results suggest that 5-HT plays a significant role in the convulsive threshold and in ACA anticonvulsant action. No correlation, however, was observed between anticonvulsant action of the studied drugs and their influence on 5-HT level in brain.


From Dibismuthenes to Three- and Two-Coordinated Bismuthinidenes by Fine Ligand Tuning: Evidence for Aromatic BiC3N Rings through a Combined Experimental and Theoretical Study.
The reduction of N,C,N-chelated bismuth chlorides [C6H3-2,6-(CH=NR)2]BiCl2 [where R = tBu (1), 2',6'-Me2C6H3 (2), or 4'-Me2NC6H4 (3)] or N,C-chelated analogues [C6H2-2-(CH=N-2',6'-iPr2C6H3)-4,6-(tBu)2]BiCl2 (4) and [C6H2-2-(CH2NEt2)-4,6-(tBu)2]BiCl2 (5) is reported. Reduction of compounds 1-3 gave monomeric N,C,N-chelated bismuthinidenes [C6H3-2,6-(CH=NR)2]Bi [where R = tBu (6), 2',6'-Me2C6H3 (7) or 4'-Me2NC6H4 (8)]. Similarly, the reduction of 4 led to the isolation of the compound [C6H2-2-(CH=N-2',6'-iPr2C6H3)-4,6-(tBu)2]Bi (9) as an unprecedented two-coordinated bismuthinidene that has been structurally characterized. In contrast, the dibismuthene {[C6H2-2-(CH2NEt2)-4,6-(tBu)2]Bi}2 (10) was obtained by the reduction of 5. Compounds 6-10 were characterized by using (1)H and (13)C NMR spectroscopy and their structures, except for 7, were determined with the help of single-crystal X-ray diffraction analysis. It is clear that the structure of the reduced products (bismuthinidene versus dibismuthene) is ligand-dependent and particularly influenced by the strength of the N→Bi intramolecular interaction(s). Therefore, a theoretical survey describing the bonding situation in the studied compounds and related bismuth(I) systems is included. Importantly, we found that the C3NBi chelating ring in the two-coordinated bismuthinidene 9 exhibits significant aromatic character by delocalization of the bismuth lone pair.


Fiber-Reinforced Viscoelastomers Show Extraordinary Crack Resistance That Exceeds Metals.
Soft fiber-reinforced polymers (FRPs), consisting of rubbery matrices and rigid fabrics, are widely utilized in industry because they possess high specific strength in tension while allowing flexural deformation under bending or twisting. Nevertheless, existing soft FRPs are relatively weak against crack propagation due to interfacial delamination, which substantially increases their risk of failure during use. In this work, a class of soft FRPs that possess high specific strength while simultaneously showing extraordinary crack resistance are developed. The strategy is to synthesize tough viscoelastic matrices from acrylate monomers in the presence of woven fabrics, which generates soft composites with a strong interface and interlocking structure. Such composites exhibit fracture energy, Γ, of up to 2500 kJ m-2 , exceeding the toughest existing materials. Experimental elucidation shows that the fracture energy obeys a simple relation, Γ = W · lT , where W is the volume-weighted average of work of extension at fracture of the two components and lT is the force transfer length that scales with the square root of fiber/matrix modulus ratio. Superior Γ is achieved through a combination of extraordinarily large lT (10-100 mm), resulting from the extremely high fiber/matrix modulus ratios (104 -105 ), and the maximized energy dissipation density, W. The elucidated quantitative relationship provides guidance toward the design of extremely tough soft composites.


[Spontaneous healing of a carotid-cavernous fistula].
In a posttraumatic carotid-sinus cavernous fistula, spontaneous healing occurred which was angiographically demonstrated. After this closure had occurred, an aneunysmal enlargement of the internal carotid was proved to exist and confirmed even two weeks later together with a concomitant spasm. The author is of the opinion that the cause of a carotid-sinus cavernous fistula is in most cases a ruptured aneurysms. By partial thrombosing of the aneurysm, a closure of the fistula occasionally takes place and thus the above mentioned spontaneous healing is reached.


[Foreign body stories].
Gastrointestinal and bronchial foreign bodies may cause significant clinical complications with a high degree of morbidity. In adults, a large variety of foreign bodies are accidentally or intentionally ingested, inserted or aspirated. In the majority of cases, the objects are expelled conservatively by coughing, vomiting or bowel movements. The risk for obstruction, perforation and penetration depends upon the type of object, those with sharp edges or tips having the highest risk. In these situations, the objects have to be removed by an endoscopic or an operative intervention. We present four foreign body stories including a young lady who swallowed a pen during sleep, a farmer who inserted a corncob into the rectum because of intractable diarrhoea, an elderly gentleman who aspirated a dental bridge while laughing and a cocain body packer who was caught at the border. Back ground, complications and removal procedures of the four cases are discussed.


Publishing and Paternalism in the Grenfell Mission: Wilfred Grenfell's Accounts of a Boy Patient and Doctor-Patient Relations in Northern Newfoundland and Labrador, 1900-14.
In 1906 Dr. Wilfred Grenfell, founder and head of the Grenfell medical mission of northern Newfoundland and southeastern Labrador, published a short article in Putnam's Monthly about a nine-year-old boy named Clem Richards, who had shot himself in the knee while hunting seabirds. The boy's identity was disclosed in full, with Grenfell including his name and image as well as a detailed description of his living conditions. The "story" of the boy's injury and recovery became a favourite of Grenfell's, and it was modified and republished in a number of magazines and books between 1906 and 1923. This article explores the appeal that Richards' accident held for Grenfell and argues that his dramatic mid-winter rescue of the boy helped Grenfell promote his mission and construct a public image of himself that would appeal to American readers and donors. By comparing published accounts with Richards' medical case record, however, we also see how much Grenfell distorted the incident to heighten its drama and reader appeal. The article also considers how the mission's dominance over northern Newfoundland and southeastern Labrador enabled Grenfell to use Richards' name and image for mission publicity with no consideration of patient consent.


Do you get what you see? The illicit doping market in Denmark-An analysis of performance and image enhancing drugs seized by the police over a 1-year period.
This study examines doping products seized by the police in three regional police districts in Denmark from December 2019 to December 2020. The products, often referred to as performance and image-enhancing drugs (PIEDs), are described in relation to the country of origin, manufacturing company, and the active pharmaceutical ingredient (API) stated on the packaging versus the one identified by subsequent chemical analysis. The study also includes a description of the degree of professionalism by which the products appear according to EU requirements. A total of 764 products were seized during the study period. The products originate from 37 countries, mainly located in Asia (37%), Europe (23%), and North America (13%). One hundred ninety-three different manufacturing companies could be identified from the product packaging. The most frequent compound class was the androgenic anabolic steroids, found in 60% of the products. In 25%-34% of the products, either no or an incorrect API relative to the one stated on the product was found. However, only 7%-10% contain either no API or a compound from a different compound class than the one stated. Most products had a professional appearance fulfilling most EU requirements for packaging information. The study shows that many different companies supply PIEDs to the Danish market and that counterfeit and substandard products are widespread. Many products do, however, appear professional to the user giving an impression of a high-quality product. Although many products are substandard, they most often contain an API from the same compound class as the one labeled.


Intracranial arterial vasospasm associated with pituitary apoplexy after head trauma--case report.
A case of intracranial arterial vasospasm caused by pituitary apoplexy after head trauma is reported. In this case, pituitary apoplexy was secondary to head trauma, and the vasospasm was thought to be due to subarachnoid hemorrhage from a pituitary tumor. No such case has previously been reported in the literature.


Prediction of recurrence in low and intermediate risk non-muscle invasive bladder cancer by real-time quantitative PCR analysis: cDNA microarray results.
The aim of the study was to define specific genetic profile in Ta and T1 urinary bladder carcinoma patients with and without recurrence by gene expression microarrays. Eleven patients with the time to recurrence shorter than one year (patients with recurrence) and 11 patients with time to recurrence longer than 4 years (patients without recurrence) were enrolled. Data from microarrays were subjected to a panel of statistical analyses to identify bladder cancer recurrence-associated gene signatures. Initial screening using the GeneSpring and Bioconductor software tools revealed a putative set 47 genes differing in gene expression in both groups. After the validation, 33 genes manifested significant differences between both groups. The significant expression was observed in the group of patients without recurrence by 30 genes of which the highest differences were detected by ANXA1, ARHGEF4, FLJ32252, GNE, NINJ1, PRICKLE1, PSAT1, RNASE1, SPTAN1, SYNGR1, TNFSF15, TSPAN1, and WDR34. These genes code for signal transduction, vascular remodeling and vascular endothelial growth inhibition mainly. In the group with recurrence, 3 genes had significant differences, the highest differences were identified by two genes (PLOD2 and WDR72). Loci of genes with significant changes of gene expression were located on characteristic chromosomes for bladder cancer: 7 loci on chromosome 9, 8 loci on chromosomes 1, 2, 3, 12,14,15,16, and 22. We have selected and validated 15 genes that are differentially expressed in superficial bladder cancer. We hope that this cohort of genes will serve as a promising pool of candidate biomarkers for early stage bladder cancer. Our results indicate that it may be possible to identify patients with a low and high risk of disease recurrence at an early stage using a molecular profile.


Developing the first dental care pathway: the oral health assessment.
In this paper the authors define the concept of care pathways and explain what they are and how they have been applied in various areas of healthcare. The authors discuss the benefits of the care pathway approach and outline the first national dental NHS (clinical) care pathway and its link to National Institute for Clinical Excellence (NICE) guidance on dental recall intervals. The authors go on to explain that as a result of one of the key recommendations of Options for Change, the concept of care pathways will be extended to the primary dental services of the NHS. The first care pathway will be the Oral Health Assessment (OHA). The authors describe the development of, and rationale for, the OHA and provide details of its planned introduction. The authors conclude that the OHA should act as the initial interface between the primary care team and the dental patient. In so doing it should enable a change in the focus of care, from treatment-based to more prevention-led, personalised care appropriate to the specific needs of individual patients.


Safety and Effectiveness of High-Dose Cefazolin in Patients With High Body Weight: A Retrospective Cohort Study.
Cefazolin is a commonly used antibiotic for the treatment of mild to severe infections. Despite the use of higher dose of cefazolin (3 g/dose) for surgical prophylaxis in patients with obesity, there is currently a paucity of data identifying the optimal dose to treat infections in this specific patient population. This was a multicenter, retrospective cohort study of patients who received cefazolin at weight-based (up to 9 g/day) or standard doses (up to 6 g/day) for the treatment of bacteremia or skin and soft tissue infection (SSTI). Study groups were stratified by body weight and cefazolin dose received. Primary outcome was the composite of treatment-emergent adverse events (TEAEs) and secondary outcome was treatment failure rate. A total of 208 patients were included for study analysis. Fifty-nine patients had body weight >120 kg. Of these, 33 received high-dose cefazolin while 26 received standard doses. The remaining 149 patients had body weight of ≤120 kg and received standard doses. The occurrence of TEAEs did not differ across the 3 groups. The study also did not find any difference between the rate of treatment failure between groups. High-dose cefazolin (9 g/day) for the treatment of bacteremia or SSTIs in patients with high body weight was safe and well tolerated. Larger studies are needed to further explore the benefit of high-dose cefazolin in improving clinical outcomes.


IA-2 antibodies--a sensitive marker of IDDM with clinical onset in childhood and adolescence. Childhood Diabetes in Finland Study Group.
To study the relationship of IA-2 antibodies (IA-2A) to other autoantibodies and genetic risk markers in insulin-dependent diabetes mellitus (IDDM), 758 children and adolescents younger than 15 years of age (mean age 8.4 years) with newly diagnosed diabetes were analysed for IA-2A, GAD antibodies (GADA) and insulin autoantibodies (IAA) with radiobinding assays, for islet cell antibodies (ICA) with immunofluorescence and for HLA DR alleles by serology. IA-2A were detected in 85.9% of cases with no association with gender or age. An overwhelming majority of the patients (71.3%) tested positive for three or more antibodies, and 90.7% for at least two. Fifty-four subjects (7.1%) had one antibody detectable, whereas only 2.1% of the patients tested negative for all four. A higher proportion of patients was positive for IA-2A and/or GADA than for ICA alone (95.5 vs 84.2%, p < 0.001). The prevalence and level of IA-2A were increased in cases carrying HLA DR4/non-DR3 compared with other DR combinations. The results indicate that almost all patients with newly diagnosed childhood IDDM can be identified by screening with these four autoantibodies. The combination of IA-2A and/or GADA had a higher sensitivity for IDDM than ICA alone. The close association between IA-2A and HLA DR4, the strongest single allele predisposing to IDDM, suggests that IA-2A may be a more specific marker of beta-cell destruction than GADA, which have been shown to associate with the DR3 allele and thyroid autoimmunity.


A Giant Schwannoma Extending from Medial Portion of Middle Cranial Fossa to Parapharyngeal Space and Deep Parotid Space.
Trigeminal schwannomas are rare tumours comprising 0.2% of all intracranial tumours and 0.5% of all head and neck tumours. Patients with trigeminal schwannomas presented with facial hypoesthesia and pain. We presented a case with left bulging oropharynx. The CT scan showed a 3.8x2.6x4.9cm left parapharyngeal tumour compressed to the oropharynx and middle cranial fossa. We performed 3 ways in two times of operation to excise the whole tumour. We chose the transoral approach for parapharyngeal space, trans-parotid approach for deep parotid part and the endoscopic endonasal trans-pterygoid approach and trans-maxillary with Canine fossa trephination for intracranial lesions. The pathology showed schwannoma. A huge schwannoma extended from intracranial to several spaces is difficult to resect just by one approach. We should separate the tumour to several parts by clinical image before the operation and design a plan to remove the whole tumour in different approach. The different space of tumour involvement had several ways to access. We needed to choose the less harm but with better surgical field.


Axonal projections of Renshaw cells in the thoracic spinal cord.
Renshaw cells are widely distributed in all segments of the spinal cord, but detailed morphological studies of these cells and their axonal branching patterns have only been made for lumbosacral segments. For these, a characteristic distribution of terminals was reported, including extensive collateralization within 1-2 mm of the soma, but then more restricted collaterals given off at intervals from the funicular axon. Previous authors have suggested that the projections close to the soma serve inhibition of motoneurons (known to be greatest for the motor nuclei providing the Renshaw cell excitation) but that the distant projections serve mainly the inhibition of other neurons. However, in thoracic segments, inhibition of motoneurons is known to occur over two to three segments (20-40 mm) from the presumed somatic locations of the Renshaw cells. Here, we report the first detailed morphological study of Renshaw cell axons outside the lumbosacral segments, which investigated whether this different distribution of motoneuron inhibition is reflected in a different pattern of Renshaw cell terminations. Four Renshaw cells in T7 or T8 segments were intracellularly labeled with neurobiotin in anesthetized cats and their axons traced for distances ≥6 mm from the somata. The only morphological difference detected within this distance in comparison with Renshaw cells in the lumbosacral cord was a minimal taper in the funicular axons, where in the lumbosacral cord this is pronounced. Patterns of termination were virtually identical to those in the lumbosacral segments, so we conclude that these patterns are unrelated to the pattern of motoneuronal inhibition.


Immigration into Europe and public policy: do stops really work?
"Using Italy as a case study, this article explores whether attempts to stop immigration can ever be effective. What it shows is that, contrary to public opinion, strict controls are not necessarily effective. Moreover, there is no evidence that the position of existing migrants improves when controls are increased. On the contrary, strict controls are associated with undermining the position of existing minorities. Such policies are particularly likely to generate the assumption that citizenship rights can only be available on ascriptive criteria."


Can living donor liver transplantation offer similar outcomes to deceased donor liver transplantation using expanded selection criteria for hepatocellular carcinoma?
To compare the outcomes of living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT) for patients with hepatocellular carcinoma (HCC) in different selection criteria. Data of patients with HCC who underwent liver transplantation between 2005 and 2013 at our center were reviewed. Clinical data of LDLT recipients and DDLT recipients were compared. The postoperative recurrence-free survival (RFS) rate and overall survival (OS) rate after LDLT versus DDLT were compared in the Milan recipients, the University of California, San Francisco (UCSF) recipients, the up-to-seven recipients, the Hangzhou recipients and the Chengdu recipients. Data of 255 patients were retrospectively reviewed in this study. Seventeen DDLT recipient and 9 LDLT recipients died during the perioperative period. Among the remaining 229 recipients (NLDLT=66, NDDLT=163), 96 patients met the Milan criteria, 123 recipients met the UCSF criteria, 135 patients met the up-to-seven criteria, 216 patients met the Hangzhou criteria, and 229 recipients met the Chengdu criteria. The overall RFS and OS rates of the Milan recipients, the UCSF recipients, the up-to-seven recipients, the Hangzhou recipients and the Chengdu recipients after LDLT and DDLT were all similar. Using well-studied selection criteria, LDLT offers similar outcomes to DDLT for patient with HCC, even using expanded selection criteria.


Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F.
The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases.


Chinese herbal formula QHF inhibits liver cancer cell invasion and migration.
The aim of the present study was to observe the effects of the Chinese herbal formula QHF (Q, Qingrejiedu; H, Huoxuehuayu; and F, Fuzhengguben) on the migration and invasion of hepatocellular carcinoma (HCC) HepG2 cells and to elucidate the potential molecular mechanisms involved. HepG2 cells were treated with various concentrations of QHF, and scratch and Transwell® migration assays were used to qualitatively analyze differences in the migration and invasion activity of these cells. Extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) inhibitors were subsequently introduced in order to study the association between QHF and the invasion of HepG2 cells. The protein expression levels of the mitogen-activated protein kinase (MAPK) signaling pathway in HepG2 cells in the presence and absence of QHF were additionally determined using western blot analysis. The results showed that QHF significantly inhibited the proliferation of the HepG2 cells in a concentration-dependent manner, in addition to inhibiting cell movement, which reduced the ability of the cells to invade and migrate. Western blot analysis indicated that the effects of QHF on HCC HepG2 cells after 24 h were to significantly decrease the expression of phosphorylated- (p-)ERK and to increase the expression of p-p38 and p-JNK; however, the total quantity of ERK, p38 and JNK protein remained unchanged. The administration of an inhibitor of ERK altered p38 and JNK expression and promoted the anti-invasion effects of QHF, whereas p38 and JNK inhibitors only partially reversed this effect. The results of the present study indicate, therefore, that QHF is able to inhibit the migratory and invasive activity of HepG2 cells. A possible underlying mechanism involves the activation of the p38 and JNK MAPK signaling pathway and the attenuation of the ERK signaling pathway.


Protective Effects of Yinchenhao Decoction on Cholesterol Gallstone in Mice Fed a Lithogenic Diet by Regulating LXR, CYP7A1, CYP7B1, and HMGCR Pathways.
The study attempted to elucidate whether lipid genes are closely associated with lipid metabolic abnormalities during the lithogenic time and how Yinchenhao Decoction (YCHD) works on the transcriptions of lipid genes against cholesterol gallstone model. C57BL/6J mice fed on lithogenic diet (LD) were used for model establishment and randomized into 5 groups. All groups received LD for different weeks with isometrically intragastric administration of YCHD or NS. Biochemical tests were measured and liver tissues were harvested for histological and genetic detection. It was found that all groups with increasing LD showed a following tendency of gallstone incidence, bile cholesterol, phospholipids, total bile acid, and cholesterol saturation index (CSI). Conversely, YCHD could significantly normalize the levels of gallstone incidence, bile lipids, and CSI (CSI<1). As lithogenic time progressed, ABCG5, ABCG8, PPAR-α, and ABCB4 were upregulated, and SREBP2, CYP7A1, and CYP7B1 were downregulated, while CYP7A1, CYP7B1, LXR, and HMGCR mRNA were increased 3-fold under the administration of YCHD. It was concluded that abnormal expressions of the mentioned genes may eventually progress to cholesterol gallstone. CYP7A1, CYP7B1, LXR, and HMGCR mRNA may be efficient targets of YCHD, which may be a preventive drug to reverse liver injury, normalize bile lipids, facilitate gallstone dissolution, and attenuate gallstone formation.


Symptoms, symptom severity, and contact with primary health care among nonhospitalized COVID-19 patients: a Norwegian web-based survey.
Dependent on clinical setting, geography and timing during the pandemic, variable symptoms of COVID-19 have been reported. Our aim was to describe self-reported symptom intensity and contact with primary health care among nonhospitalized COVID-19 patients. Web-based survey. Norway between March 2020 and July 2021. Adults in home isolation. Participants reported possible COVID-19 symptoms, duration of symptoms, score of symptom severity (Likert scale 0-3), risk factors, comorbidity, and questions regarding follow-up and information from primary health care. Of 477 participants, 379 (79%) had PCR-confirmed COVID-19, 324 (68%) were females, and 90% were younger than 60 years. Most common symptoms were "fatigue and/or muscle ache" (80%), nasal symptoms (79%), and headache (73%). The mean severity of symptoms was generally low. Symptoms with the highest mean scores were "fatigue and/or muscle ache" (1.51, SD 1.02) and headache (1.27 (SD 1.00). Mean scores for severity ranged from 0.28 (nausea) to 1.51 (fatigue and/or muscle ache). Women reported higher symptom scores than men. For "affected sense of smell and/or taste", patients either reported a high symptom score (24%) or no affliction at all (49%). A third of the participants (32%) were followed-up by primary care health personnel, and almost 40% had sought or received information about COVID-19 from general practitioners. The mean severity of symptoms among nonhospitalized adult COVID-19 patients was generally low. We found large variations in the occurrence and severity of symptoms between patients.


Trends in Prevalence of Advanced HIV Disease at Antiretroviral Therapy Enrollment - 10 Countries, 2004-2015.
Monitoring prevalence of advanced human immunodeficiency virus (HIV) disease (i.e., CD4+ T-cell count <200 cells/μL) among persons starting antiretroviral therapy (ART) is important to understand ART program outcomes, inform HIV prevention strategy, and forecast need for adjunctive therapies.*,†,§ To assess trends in prevalence of advanced disease at ART initiation in 10 high-burden countries during 2004-2015, records of 694,138 ART enrollees aged ≥15 years from 797 ART facilities were analyzed. Availability of national electronic medical record systems allowed up-to-date evaluation of trends in Haiti (2004-2015), Mozambique (2004-2014), and Namibia (2004-2012), where prevalence of advanced disease at ART initiation declined from 75% to 34% (p<0.001), 73% to 37% (p<0.001), and 80% to 41% (p<0.001), respectively. Significant declines in prevalence of advanced disease during 2004-2011 were observed in Nigeria, Swaziland, Uganda, Vietnam, and Zimbabwe. The encouraging declines in prevalence of advanced disease at ART enrollment are likely due to scale-up of testing and treatment services and ART-eligibility guidelines encouraging earlier ART initiation. However, in 2015, approximately a third of new ART patients still initiated ART with advanced HIV disease. To reduce prevalence of advanced disease at ART initiation, adoption of World Health Organization (WHO)-recommended "treat-all" guidelines and strategies to facilitate earlier HIV testing and treatment are needed to reduce HIV-related mortality and HIV incidence.


Hypoesthesia associated with mandibular movement after sagittal split ramus osteotomy.
This retrospective study investigated the relationship between the degree of neurosensory disturbance (NSD) and mandibular movement distance after sagittal split ramus osteotomy (SSRO) and assessed sensory recovery. Lower lip hypoesthesia was evaluated at 1 week, 1 month, and 2 months after SSRO in 38 patients categorized according to the distance of mandibular movement: S group (0-7 mm; n = 17, 4 males and 13 females) and L group (7-14 mm; n = 21, 7 males, 14 females). Symptoms were evaluated by visual analog scale (VAS), tactile-threshold (SW) test, static 2-point discrimination (s-2PD) test, and current perception threshold (CPT) test. The two groups did not differ significantly in gender and age. The Aβ fiber results of the CPT test differed significantly between the groups at 1 week and 1 month postsurgery (P < 0.05). There were no significant differences between the groups throughout the period in terms of VAS, SW, s-2PD, Aδ fiber, and C fiber of CPT. Post-SSRO, the incidence of NSD in terms of tactile sensation may be greater in the L group early postoperatively. This may assist surgeons in explaining postoperative hypoesthesia to patients preoperatively.


High-altitude decompression illness: case report and discussion.
Decompression illness (DCI) can occur in a variety of contexts, including scuba diving and flight in nonpressurized aircraft. It is characterized by joint pain, neurologic injury, and respiratory or constitutional symptoms. To prepare flight crews for accidental decompression events, the Canadian Armed Forces regularly conducts controlled and supervised depressurization exercises in specialized chambers. We present the cases of 3 Canadian Armed Forces personnel who successfully completed such decompression exercises but experienced DCI after they took a 3-hour commercial flight 6 hours after the completion of training. All 3 patients were treated in a hyperbaric oxygen chamber. The pathophysiology, diagnosis and management of DCI and the travel implications for military personnel who have undergone such training exercises are discussed. Although DCI is relatively uncommon, physicians may see it and should be aware of its presentation and treatment.


Family functioning and adolescents' emotional and behavioral problems: when a parent has cancer.
This article focuses on possible relationships between functioning of adolescents with a parent diagnosed with cancer 1-5 years earlier and family environment. In all, 138 patients, 114 spouses and 221 adolescents completed the Family Environment Scale. Additionally, adolescents filled in the Impact of Event Scale and Youth Self-report and parents reported on the adolescents' functioning using the Child Behavior Checklist. Patients and spouses reported that their families differ from the norm; they are more expressive and social, better organized, less controlling and have less conflict. Adolescents reported the same and additionally find their family. Family environment was weakly to moderately strongly negatively related to the adolescents' functioning; family relationships related more strongly to the adolescents' functioning than family structure did. No significant relationship was found between family environment and the adolescents' cancer-related distress. Discrepancy in reports of family environment between parents and between parents and adolescents, in general, did not relate to the adolescents' functioning or distress. Parent-adolescent discrepancy only correlated with adolescent self-reports of their functioning. Families with parental cancer functioned positively. Despite this, family functioning seems to be a risk factor for behavioral and emotional problems in adolescents.


Forecasting damaging earthquakes in the central and eastern United States.
Analysis of seismograph network data, earthquake catalogs from 1727 to 1982, and paleoseismic data for the central and eastern United States indicate that the Poisson probability of a damaging earthquake (magnitude >/= 6.0) occurring during the next 30 years is at a moderate to high level (0.4 to 0.6). When differences in seismic wave attenuation are taken into account, the central and eastern United States has approximately two-thirds the likelihood of California to produce an earthquake with comparable damage area and societal impact within the next 30 years.


Complete esophageal obstruction following endoscopic variceal band ligation.
Variceal hemorrhage is a potential complication of portal hypertension. Besides medical management, endoscopic variceal band ligation (EVBL) has emerged as a promising prophylactic tool proving to be superior to sclerotherapy. EBVL is a simple procedure associated with minor complications and short recovery time. In this report, we present a case of a rare complication of complete esophageal obstruction following an EVBL procedure. Given the high numbers of such procedures performed, it is imperative that internists and specialists be aware of this unusual complication.


Re-expansion and Stabilization of Vertebra Plana Fractures Using Bilateral SpineJack® Implants.
The surgical treatment of osteoporotic vertebral fractures with greater than 70% collapse, known as "Vertebra Plana (VP)" has been controversial. Originally VP was a considered a contraindication to vertebroplasty or kyphoplasty because of presumed difficulty of entering the collapsed vertebra as well as obtaining significant re-expansion or correct associated sagittal kyphosis. In some cases, multilevel pedicle screw fixation with or without attempts to correct the collapse is still performed to correct the kyphosis or prevent progression. With experience it was clear that the pedicle could be accessed and VP could be treated without added risk of epidural leak of cement or epidural extravasation. Now, with the introduction of newer third-generation intraspinal expansion devices that are larger and need to be placed bilaterally, their use in cases of VP was again an issue since VP cases were excluded from the original multicenter studies used for worldwide approval. This report reviews six cases of VP treated with bilateral SpineJack® implants (Stryker Corp, Kalamazoo, Michigan, USA) demonstrating it is not only feasible to place these larger size implants but achieve significant reconstitution of vertebral height as well as correction of the kyphotic deformity.


Integrating Kinetic Model of E. coli with Genome Scale Metabolic Fluxes Overcomes Its Open System Problem and Reveals Bistability in Central Metabolism.
An understanding of the dynamics of the metabolic profile of a bacterial cell is sought from a dynamical systems analysis of kinetic models. This modelling formalism relies on a deterministic mathematical description of enzyme kinetics and their metabolite regulation. However, it is severely impeded by the lack of available kinetic information, limiting the size of the system that can be modelled. Furthermore, the subsystem of the metabolic network whose dynamics can be modelled is faced with three problems: how to parameterize the model with mostly incomplete steady state data, how to close what is now an inherently open system, and how to account for the impact on growth. In this study we address these challenges of kinetic modelling by capitalizing on multi-'omics' steady state data and a genome-scale metabolic network model. We use these to generate parameters that integrate knowledge embedded in the genome-scale metabolic network model, into the most comprehensive kinetic model of the central carbon metabolism of E. coli realized to date. As an application, we performed a dynamical systems analysis of the resulting enriched model. This revealed bistability of the central carbon metabolism and thus its potential to express two distinct metabolic states. Furthermore, since our model-informing technique ensures both stable states are constrained by the same thermodynamically feasible steady state growth rate, the ensuing bistability represents a temporal coexistence of the two states, and by extension, reveals the emergence of a phenotypically heterogeneous population.


Pain in the leg: an overview.
Pain in the leg has many causes but a clinical diagnosis usually can be determined by attention to detail. A schematic approach is presented with critical questions to be asked of the patient; flow charts assist the diagnosis.


Cardioprotective effects of the proline-rich oligopeptide Bj-PRO-7a in spontaneously hypertensive rats.
The proline-rich oligopeptide from Bothrops jararaca snake venom, Bj-PRO-7a, promotes acute effects in blood pressure in hypertensive animals. However, the cardiac effects of this heptapeptide are completely unknown. Thus, we sought to evaluate whether the Bj-PRO-7a could protect against cardiac remodelling in spontaneously hypertensive rats (SHR). SHR were treated with Bj-PRO-7a (71 nmol/kg/day, s.c.) or saline for 28 days. Wistar rats were used as control. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography. Cardiomyocyte diameter and interstitial and perivascular fibrosis of the left ventricle (LV) were evaluated using Picrosirius staining. Immunofluorescence was used to detect collagen I and III. Fibroblast proliferation was assessed by immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). Protein expression was assessed by western blot. The superoxide dismutase and catalase activities and the concentration of lipid peroxidation products were evaluated in the LV. The SBP and HR were not different between treated and non-treated SHR at the end of the treatment. However, Bj-PRO-7a attenuated the cardiomyocyte hypertrophy, deposition of interstitial and perivascular fibrosis and collagen I, and positive PCNA-labelled fibroblasts. This peptide also reduced the increased levels of TBARS, expression and activity of catalase, and activity of SOD in LV from SHR. Also, the Bj-PRO-7a increased the expression of metalloproteinases-2 in SHR hearts. These findings demonstrate that the Bj-PRO-7a reduced the pathological cardiac remodelling in a pressure-independent manner in hypertensive rats through mechanisms mediated by oxidative stress regulation.


Cipadesins A-C: novel tetranortriterpenoids from Cipadessa cinerascens.
[structure: see text] Three novel tetranortriterpenoids, cipadesins A-C (1-3), were isolated from the aerial parts of Cipadessa cinerascens. They possess a novel carbon skeleton, in which rings A and C were joined via C-10 and C-11. Their structures were elucidated by spectral evidence. X-ray crystallographic analysis confirmed the structure of 1.


The novel MYB protein EARLY-PHYTOCHROME-RESPONSIVE1 is a component of a slave circadian oscillator in Arabidopsis.
Using fluorescent differential display, we identified, from approximately 8000 displayed bands, a DNA fragment showing rapid induction in response to red light irradiation. This EARLY-PHYTOCHROME-RESPONSIVE1 gene (EPR1) encodes a novel nucleus-localized MYB protein harboring a single MYB domain that is highly similar to the circadian oscillator proteins CCA1 and LHY. EPR1 is regulated by both phytochrome A and phytochrome B, and the red-light induction of EPR1 is not inhibited by cycloheximide, demonstrating that EPR1 represents a primary phytochrome-responsive gene. Our results show that EPR1 overexpression results in enhanced far-red light-induced cotyledon opening and delayed flowering. In wild-type Arabidopsis plants grown in continuous light, the EPR1 transcript exhibits circadian rhythmicity similar to that of CCA1 and LHY. Moreover, EPR1 suppresses its own expression, suggesting that this protein is part of a regulatory feedback loop. Constitutive expression of CCA1 and LHY results in the loss of EPR1 rhythmicity, whereas increased levels of EPR1 have no effect on the central oscillator. We propose that EPR1 is a component of a slave oscillator that contributes to the refinement of output pathways, ultimately mediating the correct oscillatory behavior of target genes.


Detection of infectious immune complexes in human immunodeficiency virus type 1 (HIV-1) infections: correlation with plasma viremia and CD4 cell counts.
The detection of infectious immune complexes in plasma after human immunodeficiency virus (HIV) infection may be useful as a surrogate marker of progression of disease and may help in understanding the pathogenesis of AIDS. Polyethylene glycol (PEG) precipitates of plasma were tested for the presence of HIV p24 antigen and infectious virus. Results were compared with data from cell and plasma cultures, plasma p24 antigen, CD4 cell counts, and stage of disease. PEG precipitation increased the detection rate of the p24 antigen assay from 38.3% to 58.7%. There was a significant correlation between precipitable p24 antigen and plasma viremia, changes in CD4 cell counts, and progression of disease. The sensitivity of the PEG-precipitable p24 antigen assay versus traditional p24 antigen testing was 59.0% and the specificity 91.7%. The assay was reproducible and may be a useful determinant of viral load, clinical progression, and antiretroviral efficacy.


Post-traumatic stress as a pathway to psychopathology among adolescents at high-risk for victimization.
Victimization by violence elevates adolescents' risk for developing internalizing and externalizing psychopathology. Recent findings suggest that disruptions in developmental processes associated with post-traumatic stress (PTS) reactions may partially account for the relationship between victimization and the subsequent development of psychopathology during adolescence. The present study tested the temporal sequencing of these associations using multi-informant measurements in a large, diverse sample of adolescents at high-risk for victimization. Data were collected from a multi-site consortium of prospective studies, the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN). Information about 833 youth's victimization experiences (i.e., direct, indirect, familial, and non-familial violence), PTS, and affective, anxiety, attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms were gathered from youth and their caregivers during biannual face-to-face interviews when youth were between the ages of 4 and 14 years, and continuously from official child protective services records. Structural equation modeling revealed that cumulative victimization contributed to elevations in youth and caregiver reported late childhood and early adolescent psychopathology. While PTS mediated the association between victimization and youth reported ADHD, ODD, CD, major depressive, and generalized anxiety symptoms during adolescence, it only mediated the association between victimization and caregiver reported affective symptoms. PTS reactions following childhood victimization partially accounted for escalations in psychopathology during the transition to adolescence. These findings underscore the importance of integrating trauma-informed assessment and intervention approaches with at-risk adolescents. Researchers should determine whether trauma-focused interventions sufficiently ameliorate other psychopathology among victimized adolescents or if additional interventions components are necessary.


Comparison of molecular dynamics with hybrid continuum-molecular dynamics for a single tethered polymer in a solvent.
We compare a newly developed hybrid simulation method which combines classical molecular dynamics (MD) and computational fluid dynamics (CFD) to a simulation consisting only of molecular dynamics. The hybrid code is composed of three regions: a classical MD region, a continuum domain where the dynamical equations are solved by standard CFD methods, and an overlap domain where transport information from the other two domains is exchanged. The exchange of information in the overlap region ensures that momentum, energy, and mass are conserved. The validity of the hybrid code is demonstrated by studying a single polymer tethered to a hard wall immersed in explicit solvent and undergoing shear flow. In classical molecular dynamics simulation a great deal of computational time is devoted to simulating solvent molecules, although the solvent itself is of no direct interest. By contrast, the hybrid code simulates the polymer and surrounding solvent explicitly, whereas the solvent farther away from the polymer is modeled using a continuum description. In the hybrid simulations the MD domain is an open system whose number of particles is controlled to filter the perturbative density waves produced by the polymer motion. We compare conformational properties of the polymer in both simulations for various shear rates. In all cases polymer properties compare extremely well between the two simulation scenarios, thereby demonstrating that this hybrid method is a useful way to model a system with polymers and under nonzero flow conditions. There is also good agreement between the MD and hybrid schemes and experimental data on tethered DNA in flow. The computational cost of the hybrid protocol can be reduced to less than 6% of the cost of updating the MD forces, confirming the practical value of the method.


Development of an instrument to measure attitudes of physical therapy providers working with people with dementia.
This study investigated the factor structure of an instrument to measure attitudes and beliefs of how physical therapist (PT) practitioners perceive working with people with a dementia disorder. A survey was mailed to every skilled nursing facility in Indiana (n = 495) for completion by a PT or physical therapist assistant. The survey was developed and included whether the severity of Alzheimer's disease (AD) impacts the attitudes of physical therapy practitioners. Of the 12 attitudinal questions, 11 were significant (P < .001) concerning how the severity of a diagnosis of AD (early, middle, and late) impacts attitudes of people in physical therapy practice. Principal component analysis identified 3 factors with Eigen values of 3.3 or higher accounting for 43% of the cumulative variance. These factors include professional competence, resources, and conscientiousness. This brief instrument could serve as an assessment tool to determine whether PT practitioners exhibit therapeutic nihilism when working with people with a dementia disorder.


Drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma: Current state of the art.
Transarterial chemoembolization (TACE) represents the current gold standard for hepatocellular carcinoma (HCC) patients in intermediate stage. Conventional TACE (cTACE) is performed with the injection of an emulsion of a chemotherapeutic drug with lipiodol into the artery feeding the tumoral nodules, followed by embolization of the same vessel to obtain a synergistic effect of drug cytotoxic activity and ischemia. Aim of this review is to summarize the main characteristics of drug-eluting beads (DEB)-TACE and the clinical results reported so far in the literature. A literature search was conducted using PubMed until June 2017. In order to overcome the drawbacks of cTACE, namely lack of standardization and unpredictability of outcomes, non-absorbable embolic microspheres charged with cytotoxic agents (DEBs) have been developed. DEBs are able to simultaneously exert both the therapeutic components of TACE, either drug-carrier function and embolization, unlike cTACE in which applying the embolic agent is a second moment after drug injection. This way, risk of systemic drug release is minimal due to both high-affinity carrier activity of DEBs and absence of a time interval between injection and embolization. However, despite promising results of preliminary studies, clear evidence of superiority of DEB-TACE over cTACE is still lacking. A number of novel technical devices are actually in development in the field of loco-regional treatments for HCC, but only a few of them have entered the clinical arena. In absence of well-designed randomized-controlled trials, the decision on whether use DEB-TACE or cTACE is still controversial.


Therapeutic applications of bromocriptine in endocrine and neurological diseases.
Bromocriptine, or 2-bromo-alpha-ergocryptine, is a semisynthetic ergot alkaloid. The basis of its therapeutic application in endocrine and neurological diseases is its action as a potent dopamine agonist. Its ability to inhibit prolactin secretion has led to its successful use in suppression of puerperal lactation and in the treatment of pathological hyperprolactinaemia causing galactorrhoea, infertility or hypogonadism. It has been shown to be safe in pregnancy. The ability of bromocriptine to reduce the size of large prolactin-secreting pituitary tumours has resulted in the recovery of pituitary function and correction of visual field defects. Bromocriptine is less effective in acromegaly but is useful as adjuvant therapy to radiotherapy and/or surgery which has been the standard mode of treatment. It has been shown to be efficacious either alone or in combination with levodopa in the treatment of Parkinson's disease. Therapy with low doses appears to be effective and is associated with a significantly reduced incidence of side effects. The successful use of bromocriptine has also been reported for the treatment of non-functioning pituitary tumours, premenstrual syndrome, cyclical mastalgia, luteal phase insufficiency and portal-systemic encephalopathy, although its role in the treatment of these latter disorders remains uncertain until more extensive and adequately controlled trials have been conducted.


Durability and extent of protection of SARS-CoV-2 antibodies among patients with COVID-19 in Metro Manila, Philippines.
Information on the magnitude and durability of humoral immunity against COVID-19 among specific populations can guide policies on vaccination, return from isolation and physical distancing measures. The study determined the durability of SARS-CoV-2 antibodies after an initial infection among Filipinos in Metro Manila, Philippines, and the extent of protection SARS-CoV-2 antibodies confer against reinfection. We conducted a cohort study to monitor the antibody levels of patients diagnosed with COVID-19. Receptor-binding domain (RBD)-specific antibodies were measured at Days 21, 90, 180, 270 and 360. Antibody levels were reported as geometric mean titers (GMT) with geometric standard deviation (GSD). Differences in GMT were tested using Friedman test and Kruskal Wallis test, with Bonferroni multiple comparisons procedure. Adjusted hazard ratios on the development of probable reinfection were estimated using Cox proportional models. There were 307 study participants included in the study, with 13 dropouts. Study participants received SARS-CoV-2 vaccines at varying times, with 278 participants (90.5%) fully vaccinated by the end of study. The GMT of the study cohort increased over time, from 19.7 U/mL (GSD 11) at Day 21; to 284.5 U/mL (GSD 9.6) at Day 90; 1,061 U/mL (GSD 5.3) at Day 180; 2,003 U/mL (GSD 6.7) at Day 270; and 8,403 U/mL (GSD 3.1) at Day 360. The increase was statistically significant from Day 21 to Day 90 (p<0.0001), Day 90 to Day 180 (p=0.0005), and Day 270 to Day 360 (p<0.0001). Participants with more severe initial infection demonstrated significantly higher antibody levels compared to those with milder infection at Day 21. Sixty-four patients had probable COVID-19 reinfection (incidence of 20.8%, 95% CI 16.4, 25.8%). The GMT of these 64 patients was 411.8 U/mL (GSD 6.9) prior to the occurrence of the probable reinfection. Majority (87.5%) were fully vaccinated. Antibody titers significantly affected the risk of developing reinfection, with adjusted hazard ratio of 0.994, 95% CI 0.992-0.996, p<0.001. Antibody levels against SARS-CoV-2 increased over a one-year follow-up. Higher antibody levels were observed among those with more severe initial infection and those vaccinated. Higher antibody levels are associated with a lower risk of probable reinfection.


Tissue uptake of mercury is changed during the course of a common viral infection in mice.
Mercury (Hg) has been shown to have immunotoxic effects and to influence the severity of infection. However, the impact of infection on the normal Hg homeostasis in different target organs involved in the disease process has not been studied. In this study, Hg was measured through inductively coupled plasma-mass spectrometry (ICP-MS) in the intestine, serum, liver, and brain on days 3, 6, and 9 of coxsackievirus B3 (CVB3) infection in female Balb/c mice. The severity of the infection was assessed from clinical signs of disease and the number of virus particles in infected organs. CVB3 and gene expression of metallothionein 1 (MT1) was measured by reverse transcription-polymerase chain reaction (RT-PCR). Gene expression of MT1 increased and peaked on day 3 in the brain (93%, p<0.01) and liver (19-fold, p<0.01) and on day 6 in the intestine (seven-fold, p<0.01). This peak in MT1 in the liver and brain corresponded to the peak in virus numbers in these tissues. Hg in the intestine and serum tended to decrease on all days of infection. The maximum decrease, in comparison with non-infected mice, occurred in the intestine (78%, p<0.001) on day 9 and in serum (50%, p<0.05) on day 6. However, in the brain, Hg increased by 52% (p<0.05) on day 6. Hg went unchanged in the liver. An infection-induced increase of Hg in the brain but unchanged level in the liver may be due to the peak of virus replication and an associated infection-induced expression of MT1. Moreover, the decrease of Hg in serum and the intestine but a concomitant intestinal increase in MT1 on day 6 may reflect a flux and increased retention of Hg to infected organs such as the brain. The pathophysiological interpretation of these preliminary findings requires further research.


Courts, licensing bodies turning their attention to alternative therapies.
The growing interest in alternative medicine has come to the attention of both Canadian licensing bodies and the courts. Two recent cases, a disciplinary hearing and a medical-malpractice action, illustrate that physicians need to understand the range and complexity of issues surrounding nonconventional therapies and their clinical use.


HIV infection duration, social support and the level of trauma symptoms in a sample of HIV-positive Polish individuals.
The aim of this study was to investigate the relationship between the average HIV infection duration and the level of quantitatively rated post-traumatic stress disorder (PTSD) symptoms and social support dimensions in a sample of 562 Polish HIV+ adults. Possible moderating effects of social support on the relationship between the average HIV infection duration and the level of PTSD symptoms were also analysed. The results of this study suggest that the average HIV infection duration may intensify PTSD symptoms and deteriorate the perceived availability of social support in HIV+ individuals. However, a positive relationship between HIV infection duration and the level of trauma symptoms was observed only in the group of HIV+ individuals with low perceived available social support, but not in the group of HIV-infected individuals with high perceived available social support. This research provided some new insight into the psychological and social aspects of living with HIV. In particular, our results suggest that although HIV infection duration may intensify trauma symptoms and deteriorate social support, perceived available social support may act as a buffer against HIV-related trauma symptoms.


Evidence for control of mercury accumulation rates in Canadian High Arctic lake sediments by variations of aquatic primary productivity.
Climate warming in the 20th Century has had profound effects on the limnology of High Arctic lakes, including substantial increases in autochthonous primary productivity (APP). Here, we report organic carbon and Hg core profiles from two lakes which support the hypothesis that 20th Century increases in sedimentary Hg at these latitudes were largely driven by APP increases, via Hg scavenging by algae and/or suspended detrital algal matter. Hydrocarbons quantitatively released by thermal cracking of algal-derived organic matter ("S2" carbon) were used to reconstruct past APP. Variation of S2 flux accounted for 87-91% of the variance in total Hg flux in the study lakes since 1854. Mercury and S2 carbon were also associated during the pre-Industrial Period, co-varying by as much as 30% during past warm/cool periods. As a test of the hypothesis, predicted values for 20th Century [Hg] were derived from pre-1900 Hg-S2 relationships. Measured 20th Century [Hg] was on average only 6-11% higher than that predicted in one lake, and 33% higher in the other. S2-normalization of [Hg] in the latter lake suggested that 78% of the average increase in 20th Century [Hg] could be explained by scavenging. These findings suggest that the atmospheric contribution of long-range anthropogenic Hg to High Arctic lakes may have been overestimated by several-fold because of this climate-driven process, and was responsible for no more than 22% of the 20th Century [Hg] increase in the study lakes.


Religious Attendance Moderates the Environmental Effect on Prosocial Behavior in Nigerian Adolescents.
There is a growing body of literature linking religious attendance to prosocial behavior (PB). The main purposes of the present study were to estimate genetic and environmental influences on the frequency of religious attendance (FRA) and to explore whether and how FRA moderates genetic and/or environmental influences on PB. As part of the Nigerian Twin and Sibling Study, 2860 (280 monozygotic male, 417 monozygotic female, 544 dizygotic male, 699 dizygotic female, and 920 opposite-sex dizygotic) twins (mean age = 14.2 years; SD = 1.7 years; age range = 12-18 years) completed a questionnaire regarding FRA and a PB scale. Similar to the findings from western twin samples, FRA showed substantial shared environmental influences of 74% (95% CI = 69%, 78%), with absence of genetic effects. The phenotypic correlation between FRA and PB was modest but positive and significant (r = .12; p < .01), suggesting that PB is higher among more frequent attenders than among less frequent attenders. The results of gene-environment (G × E) interaction model-fitting analysis revealed that FRA changed individual environmental experiences rather than genetic effects on PB such that while genetic variance was stable, non-shared environmental variance declined, leading the total phenotypic variance of PB to decrease with increasing levels of religious attendance.


Structure of the zinc finger domain encompassing residues 13-51 of the nucleocapsid protein from simian immunodeficiency virus.
The NCps (nucleocapsid proteins) of HIV-1 (HIV type 1), HIV-2 and SIV (simian immunodeficiency virus) are small highly basic proteins, characterized by the presence of two CCHC ZF (zinc finger) domains. NCps, closely associated with the dimeric RNA genome in the core of the virus particle, were shown to promote the specific encapsidation of the viral RNA and are implicated in reverse transcription. Solution structure of the HIV-1 NCp7 and complexes of NCp7 with RNA or DNA showed the critical relationships between the structure and its various functions. HIV-1 and HIV-2 have resulted respectively from transmissions of SIV from chimpanzees and sooty mangabeys. It has been shown that the SIVlhoest (SIV from l'Hoest monkeys) also has the potential to infect human populations. Since monkeys are of great interest for clinical studies of antiviral drugs, the structure of (13-51)NCp8 (zinc finger domain of NCp8, encompassing residues 13-51) from SIVlhoest was determined by NMR to appraise the influence of major differences in the sequence, since Glu21, Gly43 and Met46 in NCp7 are replaced by Pro, Glu and Phe respectively in this particular NCp8. The structure of (13-51)NCp8 is very well defined, and surprisingly the structure of each ZF is similar in NCp7 and NCp8. Moreover, contrary to NCp7, the two ZFs are strongly locked to each other in this NCp8. This first reported structure of a simian NCp8 compared with that of NCp7 shows that the main structural differences occur at the flexible linker between the two ZFs but the essential residues responsible for the interaction with oligonucleotides adopt the same orientation in the two proteins.


Infectious disease exposures and contact tracing in homeless shelters.
An outbreak among homeless shelter users of a communicable disease with a short generation time would pose serious public health challenges. Data from Toronto were used to examine the number of shelter residents potentially exposed in the event of such an outbreak. A shelter user had contact with a mean of 97 other residents (range, 1-292) in one day and a mean of 120 (range, 2-624) in eight days. After a single week, contact tracing becomes difficult due to the challenge of locating homeless people who have left the shelter system. Over an 8-day period, individuals who used more than one shelter had contact with an average of 98 more other shelter residents than those who stayed in a single shelter had. At the onset of a serious outbreak, it may be desirable to institute policies that strongly encourage individuals to remain at their current shelter for the duration of the outbreak.


The excitatory neurotransmitter glutamate causes filopodia formation in cultured hippocampal astrocytes.
Can neurons induce surrounding glia to provide a more favorable microenvironment? Synapses and nerve growth cones have been shown to release neurotransmitters (Hume et al. Nature 1983;305:632-634; Kater et al. Trends Neurosci. 1988;11:315-321; Young and Poo Nature 1983;305:634-637) providing a possible mechanism for this type of control. The excitatory neurotransmitter glutamate induces an increase in the number of filopodia on the surface of astrocytes cultured from the neonatal rat hippocampus. This seems to be associated with a receptor-mediated event that is activated to a lesser degree by the quisqualate and kainate, but not NMDA receptors. In addition, time-lapse video recordings have revealed a rapid extension of filopodia from the apical margins of cells treated with glutamate. The apical margins of glutamate-treated cells studied with electron microscopy contained dense cortical actin networks that are devoid of microtubules. Coated pits are often seen to invaginate from the apical membrane in the vicinity of filopodia. A receptor-binding step may be followed by a rapid reorganization of cortical actin resulting in actin-containing filopodia. This process may be mediated by inositol lipid hydrolysis. Pyramidal neurons settled on glial cultures induced filopodia to form around the entire margin of growth cones and neurite tips suggesting that these events might occur in situ.


C-H functionalization by high-valent Cp*Co(iii) catalysis.
Significant progress has been accomplished in directed C-H functionalization through the use of earth-abundant and inexpensive first-row transition metals. Among these base metals, Co is especially attractive in view of its versatile applications in C-H functionalization, in both low- and high-valent states. In this vein, catalytic Co(iii) species can be generated from the dissociation of a Cp*Co(iii) catalyst or through the oxidation of a low-valent cobalt catalyst in the presence of an oxidant. In this feature article, we will discuss the breakthroughs in Cp*Co(iii)-promoted C-H functionalization. In this field, C(sp2)-H functionalization has been extensively studied and developed. In contrast, few C(sp3)-H functionalization reactions have been reported.


Current evidence for COVID-19 therapies: a systematic literature review.
Effective therapeutic interventions for the treatment and prevention of coronavirus disease 2019 (COVID-19) are urgently needed. A systematic review was conducted to identify clinical trials of pharmacological interventions for COVID-19 published between 1 December 2019 and 14 October 2020. Data regarding efficacy of interventions, in terms of mortality, hospitalisation and need for ventilation, were extracted from identified studies and synthesised qualitatively. In total, 42 clinical trials were included. Interventions assessed included antiviral, mucolytic, antimalarial, anti-inflammatory and immunomodulatory therapies. Some reductions in mortality, hospitalisation and need for ventilation were seen with interferons and remdesivir, particularly when administered early, and with the mucolytic drug, bromhexine. Most studies of lopinavir/ritonavir and hydroxychloroquine did not show significant efficacy over standard care/placebo. Dexamethasone significantly reduced mortality, hospitalisation and need for ventilation versus standard care, particularly in patients with severe disease. Evidence for other classes of interventions was limited. Many trials had a moderate-to-high risk of bias, particularly in terms of blinding; most were short-term and some included low patient numbers.This review highlights the need for well-designed clinical trials of therapeutic interventions for COVID-19 to increase the quality of available evidence. It also emphasises the importance of tailoring interventions to disease stage and severity for maximum efficacy.


Improving Succinate Productivity by Engineering a Cyanobacterial CO2 Concentrating System (CCM) in Escherichia coli.
Biologically fixation of CO2 has great potential as a significant carbon source for biosynthesis, which is also a major way to reduce CO2 accumulation in atmosphere. Phosphoenolpyruvate (PEP) carboxylation is the key step of anaerobic succinate production in Escherichia coli. In this reaction, one mole CO2 is assimilated with PEP to form oxaloacetate by PEP carboxykinase (PCK). The preferred substrate of PCK is CO2 , which is very limited in cytoplasm. In this study, the carbon concentration mechanism (CCM) of cyanobacteria was introduced into Escherichia coli to enhance the intracellular inorganic carbon concentration for improving carboxylation velocity. Overexpression of the bicarbonate transporter (BT) or carbonic anhydrase (CA) gene from Synechococcus sp. PCC7002 led to a 22 or 35% increase in succinate titer at 36 h, respectively. The carboxylation rate of PCK increased from 2.46 to 3.92 µmol min-1 mg-1 protein by overexpression of the CA gene. In addition, co-overexpression of BT and CA genes had a synergetic effect, leading to a 44% increase in succinate titer at 36 h. This work is the first attempt to increase carbon fixation involved in microbial biosynthesis by engineering a biological CO2 delivery system, which provides new direction and strategies for improving industrial fermentations based on biological CO2 assimilation pathways.


Clinical and angiographic evaluation of the resolute zotarolimus-eluting coronary stent in Japanese patients – long-term outcome in the RESOLUTE Japan and RESOLUTE Japan small vessel study.
This study evaluated the safety and efficacy of the RESOLUTE(TM)zotarolimus-eluting stent (R-ZES; Medtronic, Inc, Santa Rosa, CA, USA) in Japanese patients for the treatment of de novo native coronary lesions. Both RESOLUTE Japan (R-Japan) and RESOLUTE Japan Small Vessel Study (R-Japan SVS) were prospective, multicenter, single-arm observational studies. R-Japan enrolled 100 patients (reference vessel diameter, 2.5-3.5 mm) and R-Japan SVS enrolled 65 patients (at least 1 lesion suitable for 2.25-mm stent) treated with R-ZES. In R-Japan, in-stent late lumen loss (LLL; the primary endpoint) at 8 months was 0.12 ± 0.22 mm and volume obstruction on intravascular ultrasound was 2.33 ± 3.51%. At 4 years, there were no cases of clinically driven target lesion revascularization (TLR); the target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, and clinically driven TLR) was 5.6% (5/90). In R-Japan SVS, in-stent LLL at 9 months was 0.27 ± 0.33 mm, TLF (primary endpoint) was 4.6% (3/65), without incidence of TLR. At 3 years, TLF was 7.9% (5/63) and clinically driven TLR, 3.2% (2/63). R-Japan and R-Japan SVS demonstrate substantial suppression of neointimal hyperplasia, low LLL, and excellent and sustained long-term clinical outcome with R-ZES in Japanese patients.


Lack of association between Toxoplasma gondii exposure and depression in pregnant women: a case-control study.
Very little is known about the link of T. gondii infection and depression. Through an age-, gender-, and month of pregnancy-matched case-control study, we determined the association of T. gondii infection and depression in pregnant women. We studied 200 pregnant women with depression and 200 pregnant women without depression attended in a public hospital in Durango City, Mexico. Pregnant women were tested for the presence of anti-Toxoplasma IgG antibodies using an enzyme-linked immunoassay (EIA), and IgG seropositive women were further tested for the presence of IgM using an EIA. IgM positivity by EIA was further analyzed by enzyme-linked fluorescence assay (ELFA). Anti-T. gondii IgG antibodies were found in 9 (4.5%) of the 200 cases and in 12 (6.0%) of the 200 controls (OR = 0.73; 95% CI: 0.30-1.79; P = 0.50). The frequency of high (>150 IU/ml) anti-T. gondii IgG levels was similar in cases and in controls (OR = 1.20; 95% CI: 0.36-4.01; P = 0.75). Two women were positive for IgM by EIA but both were negative by ELFA. We did not find serological evidence of an association between T. gondii infection and depression in pregnant women attended in a public hospital in Durango City, Mexico. Since an association of T. gondii and depression in pregnancy has been reported in the U.S. previously, further research to elucidate the role of T. gondii in prenatal depression should be conducted.


Effects of cilnidipine on serum uric acid level and urinary nitrogen monoxide excretion in patients with hypertension.
The effects of cilnidipine on the serum uric acid level and urinary NO excretion in hypertensive patients were investigated. Blood and urine samples of 16 hypertensive outpatients were collected before and 2 months after cilnidipine therapy (10 mg). The serum uric acid level decreased significantly after cilnidipine treatment, while the uric acid-creatinine clearance ratio was unaffected. The cilnidipine medication produced a significant increase in urinary NO excretion, although amlodipine did not change it significantly. Therefore, cilnidipine has a profound antihypertensive effect and may reduce the serum uric acid level and increase NO production in the kidney.


A novel homozygous loss-of-function variant in SOD1 causing progressive spastic tetraplegia and axial hypotonia.
SOD1 is the first identified causative gene for amyotrophic lateral sclerosis. Recently, a novel syndrome, presenting with severe childhood-onset spastic tetraplegia and axial hypotonia caused by the homozygous truncating variants in the SOD1 gene, is described. A 22-month-old boy was admitted with a loss of motor functions that began at the age of 9 months. Neurological was significant for axial hypotonia with spastic tetraplegia and hyperekplexia-like jerky movements. In WES, we found a novel homozygous variant (c.52_56del5ins154) in the SOD1 gene, resulting in a total loss of SOD1 mRNA expression in the real-time PCR analysis. Western blot analyses confirmed the lack of protein production. Erythrocyte superoxide dismutase enzymatic activity was nearly abolished. The heterozygous family members displayed reduced superoxide dismutase 1 protein expression and enzymatic activity (by about 40%), compared with the healthy control. Our study expanded the mutation spectrum of SOD1.


Mifepristone and misoprostol compared with misoprostol alone for induction of labor in intrauterine fetal death: A randomized trial.
To assess whether mifepristone and misoprostol are more beneficial than misoprostol alone for the induction of labor in women with intrauterine fetal death. A randomized double blind placebo-controlled parallel group superiority trial was conducted. One hundred and ten women who had experienced fetal death at or later than 20 weeks of gestation were randomized by computer-generated random number sequence to receive 200 mg of mifepristone or matched placebo tablets orally. Misoprostol was administered vaginally to women of both groups after 36-48 h. The main outcomes studied were the fetal-placental delivery rate within 24 hours of commencement of the first dose of misoprostol without additional intervention and the induction-delivery interval. Successful delivery occurred significantly more frequently in women who received mifepristone prior to misoprostol than in women who received only misoprostol (92.5% [49/53] compared with 71.2% [37/52] respectively; P = 0.001). The mean induction-delivery interval was also significantly shorter when using mifepristone plus misoprostol than using misoprostol alone (9.8 h, standard deviation, 4.4 compared with 16.3 h standard deviation, 5.7, respectively; P < 0.001). Use of a combination of mifepristone and misoprostol significantly improved the rate of successful delivery and shortened the induction-delivery interval in women who had experienced fetal death compared with the use of misoprostol alone.


A linear-scaling spectral-element method for computing electrostatic potentials.
A new linear-scaling method is presented for the fast numerical evaluation of the electronic Coulomb potential. Our approach uses a simple real-space partitioning of the system into cubic cells and a spectral-element representation of the density in a tensorial basis of high-order Chebyshev polynomials. Electrostatic interactions between non-neighboring cells are described using the fast multipole method. The remaining near-field interactions are computed in the tensorial basis as a sum of differential contributions by exploiting the numerical low-rank separability of the Coulomb operator. The method is applicable to arbitrary charge densities, avoids the Poisson equation, and does not involve the solution of any systems of linear equations. Above all, an adaptive resolution of the Chebyshev basis in each cell facilitates the accurate and efficient treatment of molecular systems. We demonstrate the performance of our implementation for quantum chemistry with benchmark calculations on the noble gas atoms, long-chain alkanes, and diamond fragments. We conclude that the spectral-element method can be a competitive tool for the accurate computation of electrostatic potentials in large-scale molecular systems.


Cooperative effects for CYP2E1 differ between styrene and its metabolites.
Cooperative interactions are frequently observed in the metabolism of drugs and pollutants by cytochrome P450s; nevertheless, the molecular determinants for cooperativity remain elusive. Previously, we demonstrated that steady-state styrene metabolism by CYP2E1 exhibits positive cooperativity. We hypothesized that styrene metabolites have lower affinity than styrene toward CYP2E1 and limited ability to induce cooperative effects during metabolism. To test the hypothesis, we determined the potency and mechanism of inhibition for styrene and its metabolites toward oxidation of 4-nitrophenol using CYP2E1 Supersomes® and human liver microsomes. Styrene inhibited the reaction through a mixed cooperative mechanism with high affinity for the catalytic site (67 µM) and lower affinity for the cooperative site (1100 µM), while increasing substrate turnover at high concentrations. Styrene oxide and 4-vinylphenol possessed similar affinity for CYP2E1. Styrene oxide behaved cooperatively like styrene, but 4-vinylphenol decreased turnover at high concentrations. Styrene glycol was a very poor competitive inhibitor. Among all compounds, there was a positive correlation with binding and hydrophobicity. Taken together, these findings for CYP2E1 further validate contributions of cooperative mechanisms to metabolic processes, demonstrate the role of molecular structure on those mechanisms and underscore the potential for heterotropic cooperative effects between different compounds.


[Gynecological care to children and adolescents. Twelve-year experience at National Pediatrics Institute, Mexico].
In major regions of the world, the importance of gynecological care to children and adolescents has been recognized. There are multiple publications, journals and associations dedicated to this purpose. In Mexico, it has not been the case. The aim of this publication is to raise awareness to the medical community about the importance of sub specialized gynecological care to children and adolescents. Retrospective study. The number of office evalu- ations issued by the Department of Gynecology of the National Institute of Pediatrics (INP) from January 1, 2002 to December 31, 2013 were counted. Results were grouped by age groups. Group 1: 1 year or less. Group 2: 2 to 9 years. Group 3: 10 to 18 years. The major causes of morbidity were analyzed by groups and in general. In the 12 year period reported, 21,190 girls granted gynecological consultation: 15.2% were first consultations (n = 3,221), 74.76% subsequent consultations (n = 15,842) and 10.04% evaluations and interconsultations (n = 2,127). The yearly average was 1,766 consultations. From 2002 to 2005, two certififyed obstetrician-gynecologists (OB-GYN) worked in the Departament, with the subsecuent increase in the number of attentions; 2005 was the year with the highest productivity (2,265). From 2006, only one OB-GYN continued laboring, and the number of visits decreased gradually. 2013 was the year with fewer productivity (1,351). The main causes of morbidity were: abnormal uterine bleeding (26.48%), inflammatory conditions of vagina and vulva (13.58%), dysmenorrhea (12.31%); which occupied 52.37% of the total (10,404 / 19,867). 81% of the patients corresponded to group 3 (17,079/21,190). To a younger patient, corresponded a smaller number of visits. It is required to institute the subspecialty of Child and Adolescent Gynecology in Mexico and to establish Services formed by subspecialists in this matter in the top pediatric hospitals of the country.


Tracking atrophy progression in familial Alzheimer's disease: a serial MRI study.
Serial MRI scanning of autosomal dominant mutation carriers for Alzheimer's disease provides an opportunity to track changes that could predate symptoms or clinical diagnosis of the disease. We used hierarchical modelling to assess how hippocampal and whole-brain volumes change as familial Alzheimer's disease progresses from the presymptomatic stage through to diagnosis. Nine mutation carriers had serial clinical assessments and volumetric MRI scans (41 scans: range 3-8 per patient) at different clinical stages (presymptomatic, mild cognitive impairment, or clinical Alzheimer's disease). 25 healthy controls had serial scanning (54 scans: range 2-4 per patient) for comparison. We measured whole brain and total hippocampal volumes using semi-automated techniques, and adjusted for total intracranial volume. Hierarchical models were developed to estimate differences in volume and atrophy rate between mutation carriers and controls in relation to when the disease was clinically diagnosed. Mutation carriers had significantly increased hippocampal and whole-brain atrophy rates compared with controls and these differences increased with time. Differences in hippocampal and whole-brain atrophy rates between controls and mutation carriers were evident 5.5 and 3.5 years, respectively, before diagnosis of Alzheimer's disease. At a cross-sectional level, differences in mean hippocampal volume between mutation carriers and controls became significant 3 years before clinical diagnosis, whereas differences in mean brain volumes became significant only 1 year before diagnosis. Structural changes can be seen on MRI scans that predate the clinical onset of familial Alzheimer's disease. Longitudinal measures of atrophy rates can identify differences between mutation carriers and controls 2-3 years earlier than cross-sectional volumetric measures.


Comparative stereological studies on zonation and cellular composition of adrenal glands of normal and anencephalic human fetuses. II. Cellular composition of the gland.
In our previous paper (Bocian-Sobkowska et al., 1997) we demonstrated a striking difference in development of zonation in adrenals of normal and anencephalic human fetuses. The purpose of the present study was to characterize, by means of stereology, the cellular composition of developing adrenals in the same case. Studies were performed on 11 pairs of adrenal glands from normal fetuses and 10 from anencephalic fetuses. In the studied period of development (24 to 39 weeks of intra-uterine life) the average volume of cells in normal glands increased as follows: zona glomerulosa (ZG) from 355 to 870 microns3; zona fasciculata (ZF) from 779 to 1200 microns3; fetal zone (FZ) from 2004 to 2380 microns3: and medulla (M) from 600 to 970 microns3. In anencephalic fetuses, the appropriate values were: ZG-380-680 microns3; ZF-460-680 microns3; FZ-1820-1680 microns3; and M-870-1400 microns3. At the end of the studied period the number of ZG cells in normal fetuses was two fold higher than in anencephalics, ZF cells-6-fold and in FZ-5-fold higher, while in the M the number of cells was nearly equal in both groups. During the whole investigated period of intra-uterine development the total number of adrenocortical cells in normal glands increased ca 2.5-fold, while in anencephalic glands only ca 0.5-fold, reaching at the end ca 40% of normal value. In both normal and anencephalic adrenals the number of ZG and M cells was highly correlated with ZG/M cell ratio, being slightly higher in normal glands. No such relation was demonstrated for cells of the remaining adrenocortical zones.


Recent Investigations for Discovery of Natural Antioxidants: A Comprehensive Review.
In the biological system, reactive oxygen species (ROS) play a crucial role in the defense mechanisms of the body. ROS is responsible for the initiation of several cellular responses that can impart the harmful effects on the body, initiating biomolecular damage. Therefore, it is essential to counteract the dangerous effects produced by ROS, which is only possible through the use of antioxidants. Researchers are evaluating medicinal plants to discover and investigate the new antioxidant sources. Using natural antioxidants, beneficial effects on human health can be achieved. In this article, we summarize the recent investigations of the sources of naturally occurring antioxidants.


New Jersey Center for Tourette Syndrome sharing repository: methods and sample description.
Tourette Syndrome is a neuropsychiatric disorder characterized by chronic motor and phonic tics. Affected individuals and their family members are at an increased risk for other neuropsychiatric conditions including obsessive-compulsive disorder and attention deficit hyperactivity disorder. While there is consistent evidence that genetic factors play a significant etiologic role, no replicable susceptibility alleles have thus far been identified. Here we discuss a sharing resource of clinical and genetic data, the New Jersey Center for Tourette Syndrome Sharing Repository, whose goal is to provide clinical data, DNA, and lymphoblastoid cell lines to qualified researchers. Opening access to the data and patient material to the widest possible research community will hasten the identification of causal genetic factors and facilitate better understanding and treatment of this often impairing disorder.


Unusual cause of airway obstruction: subglottic oncocytic cyst.
Oncocytic cysts are rare benign cystic lesions, which are usually seen in the supraglottic region. They usually present with symptoms of hoarse voice or the sensation of a lump in the throat. Management is with complete excision and follow-up to monitor for recurrence. In this unusual case, an elderly woman presenting with shortness of breath following recent treatment for pneumonia developed rapidly worsening stridor during admission. Flexible nasal endoscopy revealed a large pedunculated cystic lesion arising from the subglottic laryngeal mucosa. A tracheostomy was performed as an emergency and the lesion was then excised. Histology confirmed the diagnosis of a benign oncocytic cyst. Although oncocytic cysts are a recognised benign pathology of the supraglottic larynx, they should remain in the differential diagnosis for the subglottic larynx. Management is based on cases of supraglottic pathology, and we advise careful monitoring for this previously unreported pathology.


Areawide chemical contamination. Lessons from case histories.
Nine case histories illustrate the mounting problems owing to chemical contamination that often extends beyond the workplace into the community. The effects include not only carcinogenesis and teratogenesis, so much in the public's mind, but also severe neurological and gonadal disabilities immediately after exposure. Recognition of causal relationships is often made by astute clinicians. The experience of the Atomic Bomb Casualty Commission in studying Japanese survivors in Hiroshima and Nagasaki serves as a model for future studies of communities exposed to unusual environmental contamination.


Early evaluation of the Food and Drug Administration (FDA) guidance on antimicrobial use in food animals on antimicrobial resistance trends reported by the National Antimicrobial Resistance Monitoring System (2012-2019).
Antimicrobial resistance (AMR) is one of the biggest challenges to global public health. To address this issue in the US, governmental agencies have implemented system-wide guidance frameworks and recommendations aimed at reducing antimicrobial use. In particular, the Food and Drug Administration (FDA) prohibited the extra-label use of cephalosporins in food animals in 2012 and issued the guidance for industry (GFI) #213 about establishing a framework to phase out the use of all medically relevant drugs for growth promotion in 2012. Also in 2015, the FDA implemented veterinary feed directive (VFD) drug regulations (GFI# 120) to control the use of certain antimicrobials. To assess the potential early effects of these FDA actions and other concurrent antimicrobial stewardship actions on AMR in the food chain, we compared the patterns of the phenotypic (minimum inhibitory concentration (MIC) and percentage of resistance) and genotypic resistances for selected antimicrobials before and after 2016 across different enteric pathogen species, as reported by the National Antimicrobial Resistance Monitoring System (NARMS). Most of the antimicrobials analyzed at the phenotypic level followed a downward trend in MIC after implementing the guidance. Although, most of those changes were less than one 1-fold dilution. On the other hand, compared to MIC results, the results based on phenotypic resistance prevalence evidenced higher differences in both directions between the pre- and post-guidance implementation period. Also, we did not find relevant differences in the presence of AMR genes between pre- and post-VFD drug regulations. We concluded that the FDA guidance on antimicrobial use has not led to substantial reductions in antimicrobial drug resistance yet.


Predicting myelinated axon activation using spatial characteristics of the extracellular field.
The computation time required for modeling the nonlinear response of an axon to an applied electric field is a significant limitation to optimizing a large number of neural interface design parameters through use of advanced computer algorithms. This paper introduces two methods of predicting axon activation that incorporate a threshold that includes the magnitude of the extracellular potential to achieve increased accuracy over previous computationally efficient methods. Each method uses a modified driving function that includes the second spatial difference of the applied extracellular voltage to predict the electrical excitation of a nerve. The first method uses the second spatial difference taken at a single node of Ranvier, while the second uses a weighted sum of the second spatial differences taken at all nodes of Ranvier. This study quantifies prediction accuracy for cases with single and multiple point source stimulating electrodes. While both new methods address the major criticism of linearized prediction models, the weighted sum method provides the most robust response across single and multiple point sources. These methods improve prediction of axon activation based on properties of the applied field in a computationally efficient manner.


[Changing seroepidemiology pattern of hepatitis B virus infection among elementary and junior high school children in Keelung, Taiwan, 1988].
A large-scale seroepidemiologic study of 20816 (35.6% of total) elementary and junior high school children (grades 1-9) in Keelung, Taiwan was conducted in April-May 1988. The study was to investigate the current status of hepatitis B virus (HBV) infection and to plan the extension of the present HBV prevention program to other age groups. Two HBV markers, hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs), were determined by enzyme immunoassay. The overall seropositivity rates of HBsAg and anti-HBs were 19.0% and 25.6%, respectively. Only 0.4% of the children studied were concurrently positive for both HBsAg and anti-HBs and 55.8% of them were negative for these two markers. It is noteworthy that the seropositivity rate of HBsAg increased with increasing age, from 15.4% in grade 1 (ages 6) to 23.7% in grade 9 (ages 15). This rate of HBsAg was not higher than the 1986 findings (14.0-25.5%) screened from children (4-13 years old) in Keelung, by comparing each age cohort strata, even though the age of study population was two years older. These data indicate that the current hepatitis control strategies have resulted in the reduction of the hepatitis B carrier rate among children from more than 20% to 15% at age 6 (grade 1) in Keelung, but the reduction is still higher than in Taipei children (10%). The seropositivity rate of anti-HBs was also increased with increasing age, from 13.5% (grade 1) to 44.1% (grade 9) and was similar to previous findings in Taiwan.(ABSTRACT TRUNCATED AT 250 WORDS)


The use of pronase enhances sensitivity of the PAP method in the detection of intracytoplasmic immunoglobulins.
Application of immunocytochemistry to formalin-fixed, paraffin-embedded material tends to provide capricious results, even when employing the unlabelled antibody peroxidase-antiperoxidase (PAP) method. This study shows that treatment of tissue sections with pronase, a protease isolated from a strain of Streptomyces griseus, prior to performance of the PAP procedure greatly enhances its sensitivity. The optimum conditions for use of this enzyme in detecting intracellular immunoglobulins are given.


Metabolic and nutritional complications of bariatric surgery : a review.
Bariatric surgery is considered as the only effective durable weight-loss therapy and may be curative for obesity-related comorbidities such as diabetes. Nevertheless this surgery is not devoid of potential long-term complications such as dumping syndrome, gastroesophageal reflux disease and nutrient deficiencies. For this reason, preoperative nutritional assessment and rigorous postoperative follow-up with administration of multi-vitamins supplements and assessment of serum levels is recommended for each patient who is undergoing a bariatric surgery. The aim of this review is to identify and treat the metabolic and nutritional complications of bariatric surgery.


Dynamics and interactions of cobalamin and folate status during advanced aging - a longitudinal study in a community-dwelling cohort with multiple follow-ups.
Older people are reported to be prone to imbalances between cobalamin and folate status with possible adverse effects on health. This longitudinal study investigates dynamics and interactions of cobalamin and folate status in a cohort of community-dwelling older adults by considering possible influencing factors. In total, 332 subjects ≥ 60 years were investigated over a mean observation period of 12 years. Data collection included serum cobalamin, folate and creatinine, dietary intakes of cobalamin, folate and alcohol, use of supplements, body composition, smoking behavior, and diseases. Linear mixed-effects models with repeated measurements were used to investigate the influence of variables on serum cobalamin and folate. At baseline, median cobalamin intake exceeded the dietary reference value (DRV), while median folate intake was considerably below DRV. In most subjects, serum concentrations of both vitamins were within reference ranges. For serum cobalamin, apart from supplement use (Parameter estimate [95% confidence interval]: 130.17 [53.32, 207.01]), the main positive predictor was serum folate (4.63 [2.64, 6.62]). For serum folate, serum creatinine (10.85 [4.85, 16.86]), use of supplements (7.86 [5.05, 10.67]), serum cobalamin (0.01 [< 0.01, 0.01]), and dietary folate intake (0.02 [0.01, 0.03]) were positive predictors. No main effects of age, sex, body composition, alcohol intake or smoking were found after adjusting for simultaneous inference. Advancing age, per se, is no risk factor for a decline in serum concentrations of cobalamin or folate in subjects ≥ 60 years. Suboptimal folate intake may limit the function of folate regarding the supply of methyl groups for methylation of cobalamin and subsequent creatine biosynthesis. The positive association of serum creatinine with folate deserves further exploration with regard to its possible relevance for maintaining energy dependent functional integrity in the course of ageing.