[Dentist and scientific dental information in mass media].
Mass media, such as newspapers and magazines and to a lesser degree TV and radio can provide the public with a lot of scientific information about dental diseases. Especially when it concerns research results with news value or controversial issues. Dentists regarded by the public as the most reliable sources of scientific information about dentistry, can get into problems by the publication of such issues in mass media. Particularly when patients ask questions about developments in certain fields of dentistry (for example periodontology or implantology) covered by the mass media. In this article the importance and the value of communication of scientific information are discussed. The relevance for dentistry is illustrated by means of a series of articles on scientific dental subjects published, during fifteen years, in a Dutch national newspaper. Finally the responsibility of dental faculties and professional organisations when they provide research results to the press and other mass media is pointed out.


Impact of carbapenem resistance and receipt of active antimicrobial therapy on clinical outcomes of Acinetobacter baumannii bloodstream infections.
Nosocomial Acinetobacter baumannii bloodstream infections occur with significant prevalence and mortality. The relationship between carbapenem resistance in A. baumannii and patient outcomes remains unclear. A retrospective cohort study was conducted on patients with A. baumannii bacteremia. Outcomes, controlling for confounders, were compared for carbapenem-nonresistant A. baumannii (CNRAB) and carbapenem-resistant A. baumannii (CRAB). The primary outcome studied was all-cause hospital mortality, and the secondary endpoints evaluated were time to mortality, time to negative cultures, and length of stay postinfection for survivors. A total of 79 patients, 37 infected with CRAB and 42 with CNRAB, were studied. Hospital mortality was greater in the CRAB group as determined based on bivariate analysis (P < 0.01); however, this effect was nullified when controlling for relevant confounders with logistic regression and a Cox proportional-hazards model (P = 0.71 and 0.75, respectively). Values for time to mortality and time to negative cultures did not differ between the groups. The median number of days of stay postinfection for survivors was greater for the CRAB group than the CNRAB group (14 versus 6.5; P < 0.01). Patients who received active antimicrobial therapy were less likely to die (93.5% versus 74.2%; P = 0.02), regardless of carbapenem susceptibility classifications, and this result was robust in the multivariate model (P = 0.02). Trends existed for improved outcomes in patients receiving an active beta-lactam, and patients fared worse if they had received a polymyxin as an active agent. Patients with CRAB bloodstream infections were more chronically ill and had more comorbidities. Inactive therapy was more important than carbapenem susceptibility with respect to outcomes, was a strong predictor of death, and is potentially modifiable.


Fitness for work in employeers exposed to ionizing radiations with an increased susceptibility to malignancies.
The assessment of fitness for work regarding employees exposed to ionizing radiations and with an increased susceptibility to malignancies requires a particularly complex procedure. To determine, where possible, parameters for the assessment of fitness for work of employees exposed to ionizing radiations, who have increased susceptibility to malignancies. To set out suitable criteria for the assessment of fitness for work. Existing laws, technical standards, scientific literature and publications issued by international organizations and dealing with the health and safety of workers exposed to radiations may help establish criteria to inform assessment of fitness for work. Taking into account the concept of acceptable risk, the application of objective criteria as well as of subjective considerations may allow professionals to make individualised assessments of fitness for work.


Fibrinolytic potential and antiphospholipid antibodies in systemic lupus erythematosus and other connective tissue disorders.
We studied the fibrinolytic response before and after venous occlusion (VO) in 30 patients with systemic lupus erythematosus (SLE), 25 with rheumatoid arthritis (RA) and 25 with different connective tissue disorders. Results were compared in patients with and without antiphospholipid antibodies (APA) and a history of either thrombosis or abortions. Before occlusion plasma levels of tissue-type plasminogen activator (t-PA) antigen and its inhibitor (PAI-1) were significantly higher in the patient group (p < 0.001). After occlusion, a low fibrinolytic activity on fibrin plates (p < 0.005) was observed in the same group. t-PA capacity and t-PA release were similar in relation to controls. The plasma PAI-1 activity was significantly elevated in each group of patients (p < 0.005) as compared to the control group. No significant differences with respect to t-PA and PAI-1 were observed in patients as to the presence or absence of thrombosis. There was also no correlation between the fibrinolytic changes and the presence of APA. It is concluded that an impairment of the fibrinolytic system, mainly related to increased PAI-1 levels, is present in most patients with connective tissue disorders, although these changes did not correlate with the presence of APA or the incidence of thrombosis.


Influence of total-body mass on the scaling of S-factors for patient-specific, blood-based red-marrow dosimetry.
To perform patient-specific, blood-based red-marrow dosimetry, dose conversion factors (the S factors in the MIRD formalism) have to be scaled by patients' organ masses. The dose to red marrow includes both self-dose and cross-irradiation contributions. Linear mass scaling for the self-irradiation term only is usually applied as a first approximation, whereas the cross-irradiation term is considered to be mass independent. Recently, the need of a mass scaling correction on both terms, not necessarily linear and dependent on the radionuclide, has been highlighted in the literature. S-factors taking into account different mass adjustments of organs are available in the OLINDA/EXM code. In this paper, a general algorithm able to fit the mass-dependent factors S(rm<--tb) and S(rm<--rm) is suggested and included in a more general equation for red-marrow dose calculation. Moreover, parameters to be considered specifically for therapeutic radionuclides such as (131)I, (90)Y and 177Lu are reported. The red-marrow doses calculated by the traditional and new algorithms are compared for (131)I in ablation therapy (14 pts), 177Lu- (13 pts) and (90)Y- (11 pts) peptide therapy for neuroendocrine tumours, and (90)Y-Zevalin therapy for NHL (21 pts). The range of differences observed is as follows: -36% to -10% for (131)I ablation, -22% to 5% for 177Lu-DOTATATE, -9% to 11% for (90)Y-DOTATOC and -8% to 6% for (90)Y-Zevalin. All differences are mostly due to the activity in the remainder of the body contributing to cross-irradiation. This paper quantifies the influence of mass scaling adjustment on usually applied therapies and shows how to derive the appropriate parameters for other radionuclides and radiopharmaceuticals.


Biochemical and molecular characterization of the Clostridium magnum acetoin dehydrogenase enzyme system.
E2 (dihydrolipoamide acetyltransferase) and E3 (dihydrolipoamide dehydrogenase) of the Clostridium magnum acetoin dehydrogenase enzyme system were copurified in a three-step procedure from acetoin-grown cells. The denatured E2-E3 preparation comprised two polypeptides with M(r)s of 49,000 and 67,000, respectively. Microsequencing of both proteins revealed identical amino acid sequences. By use of oligonucleotide probes based on the N-terminal sequences of the alpha and beta subunits of E1 (acetoin dehydrogenase, thymine PPi dependent), which were purified recently (H. Lorenzl, F.B. Oppermann, B. Schmidt, and A. Steinbüchel, Antonie van Leeuwenhoek 63:219-225, 1993), and of E2-E3, structural genes acoA (encoding E1 alpha), acoB (encoding E1 beta), acoC (encoding E2), and acoL (encoding E3) were identified on a single ClaI restriction fragment and expressed in Escherichia coli. The nucleotide sequences of acoA (978 bp), acoB (999 bp), acoC (1,332 bp), and acoL (1,734 bp), as well as those of acoX (996 bp) and acoR (1,956 bp), were determined. The amino acid sequences deduced from acoA, acoB, acoC, and acoL for E1 alpha (M(r), 35,532), E1 beta (M(r), 35,541), E2 (M(r), 48,149), and E3 (M(r), 61,255) exhibited striking similarities to the amino acid sequences of the corresponding components of the Pelobacter carbinolicus acetoin dehydrogenase enzyme system and the Alcaligenes eutrophus acetoin-cleaving system, respectively. Significant homologies to the enzyme components of various 2-oxo acid dehydrogenase complexes were also found, indicating a close relationship between the two enzyme systems. As a result of the partial repetition of the 5' coding region of acoC into the corresponding part of acoL, the E3 component of the C. magnum acetoin dehydrogenase enzyme system contains an N-terminal lipoyl domain, which is unique among dihydrolipoamide dehydrogenases. We found strong similarities between the AcoR and AcoX sequences and the A. eutrophus acoR gene product, which is a regulatory protein required for expression of the A. eutrophus aco genes, and the A. eutrophus acoX gene product, which has an unknown function, respectively. The aco genes of C. magnum are probably organized in one single operon (acoABXCL); acoR maps upstream of this operon.


Automatic laser welding and milling with in situ inline coherent imaging.
Although new affordable high-power laser technologies enable many processing applications in science and industry, depth control remains a serious technical challenge. In this Letter we show that inline coherent imaging (ICI), with line rates up to 312 kHz and microsecond-duration capture times, is capable of directly measuring laser penetration depth, in a process as violent as kW-class keyhole welding. We exploit ICI's high speed, high dynamic range, and robustness to interference from other optical sources to achieve automatic, adaptive control of laser welding, as well as ablation, achieving 3D micron-scale sculpting in vastly different heterogeneous biological materials.


Quality of life related to oral, subcutaneous, and intravenous biologic treatment of inflammatory bowel disease: a time trade-off study.
Novel oral treatments (including biologics) of inflammatory bowel disease (IBD) are emerging. Apart from improvement of health, treatment convenience may be of value to patients. This 'process utility' can be estimated under the quality-of-life framework. We investigated the process utility associated with subcutaneous and intravenous biologic treatments compared with a hypothetical oral biologic treatment of IBD. A time trade-off study to estimate utilities for health states among adult patients with IBD was carried out. Respondents rated the anchor state (no description of the route of administration; the reference) and three states described: the once-daily oral, 2-weekly subcutaneous, and 8-weekly intravenous administration of biologic treatment for advanced IBD. Data from 127 respondents (age, 34.4 years; women, 52.9%) were collected. The oral state was valuated higher than the anchor state more frequently than subcutaneous and intravenous states (P=0.001). The process utility of the oral state adjusted for confounders was estimated at 0.147 (95% confidence interval: 0.087-0.208) and 0.164 (95% confidence interval: 0.096-0.233) in comparison with subcutaneous and intravenous states, respectively. The results were consistent across the respondents irrespective of their characteristics and unaffected by the change in the assumptions of data analysis. Oral administration is preferred over the available routes of administration of biologics by patients with IBD. The utility gains from oral treatment were significant, indicating higher value of that treatment within a cost-utilitarian approach. The additional process-related benefit can justify higher expenditures for the research of oral biologics.


Quinolone-induced psychosis: an updated review.
Quinolones are an antibiotic group widely used due to their antimicrobial action and security profile, however, it has been described neuropsychiatric adverse effects, being induced-psychotic episodes one of the most clinically relevant. Nevertheless, this secondary effect has been scarcely studied. A literature search using PRISMA guidelines was performed between 01/01/1962 and 01/31/2019 on PubMed and ScienceDirect, including manuscripts which described substance-induced psychotic disorder according to DSM-5 and in which the symptomatology was not attributable to an acute confusional state (delirium) or to other induced psychiatric disorders. 459 articles were found, but only 27 manuscripts fulfilled inclusion criteria (n=27 patients, median age of 36.15±16.96 years). Ciprofloxacin, levofloxacin and ofloxacin were the main antibiotics implicated. Quinolone- induced psychosis is a clinical relevant issue due to the high prescription of these antibiotics and the severity of this clinical syndrome. In general, this syndrome can remit in a few days with the withdrawal of the quinolone and performing symptomatic support if it is necessary. Finally, it is important to perform further research on this issue. Keywords: Quinolones, Psychosis, Ciprofloxacin, Levofloxacinn, Psychotic Induced.


Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord.
The infusion of BDNF and NT-3 into Schwann cell (SC) grafts promotes regeneration of brainstem neurones into the grafts placed in adult rat spinal cord transected at T8 (Xu et al., 1995b). Here, we compared normal SCs with SCs genetically modified to secrete human BDNF, grafted as trails 5 mm long in the cord distal to a transection site and also deposited in the transection site, for their ability to stimulate supraspinal axonal regeneration beyond the injury. SCs were infected with the replication-deficient retroviral vector pL(hBDNF)RNL encoding the human preproBDNF cDNA. The amounts of BDNF secreted (as detected by ELISA) were 23 and 5 ng/24 h per 106 cells for infected and normal SCs, respectively. Biological activity of the secreted BDNF was confirmed by retinal ganglion cell bioassay. The adult rat spinal cord was transected at T8. The use of Hoechst prelabelled SCs demonstrated that trails were maintained for a month. In controls, no SCs were grafted. One month after grafting, axons were present in SC trails. More 5-HT-positive and some DbetaH-positive fibres were observed in the infected vs. normal SC trails. When Fast Blue was injected 5 mm below the transection site (at the end of the trail), as many as 135 retrogradely labelled neurones could be found in the brainstem, mostly in the reticular and raphe nuclei (normal SCs, up to 22, mostly in vestibular nuclei). Numerous neurones were labelled in the ventral hypothalamus (normal SCs, 0). Also, following Fast Blue injection, a mean of 138 labelled cells was present in dorsal root ganglia (normal SCs, 46) and spinal cord (39 vs. 32) rostral to the transection. No labelled spinal neurones rostral to the transection were seen when SCs were not transplanted. Thus, the transplantation of SCs secreting increased amounts of BDNF improved the regenerative response across a transection site in the thoracic cord. Moreover, the enhanced regeneration observed with infected SCs may be specific as the largest response was from neurones known to express trkB.


US Assessment of Sports-related Hip Injuries.
Traumatic and overuse hip injuries occur frequently in amateur and professional athletes. After clinical assessment, imaging plays an important role in diagnosis and in defining care management of these injuries. Ultrasonography (US) is being increasingly used in assessment of hip injuries because of the wide availability of US machines, the lower cost, and the unique real-time imaging capability, which allows both static and dynamic evaluation as well as guidance of point-of-care interventions such as fluid aspiration and steroid injection. Accurate diagnosis of hip injuries is often challenging, given the complex soft-tissue anatomy of the hip and the wide spectrum of injuries that can occur. To conduct a skillful US evaluation of hip injuries, physicians must have pertinent knowledge of the normal anatomy and should make judicious use of surface anatomy landmarks while using a compartmentalized diagnostic approach. In this article, common sports-related injuries of the anterior, lateral, and posterior hip compartments are discussed. This review includes assessment of joint effusion, acetabular labral tear, acute and chronic tendon injuries including tendinopathy, partial and full-thickness tears, snapping hip syndromes, relevant US-guided procedures, and some other conditions such as Morel-Lavallée lesion and perineal nodular induration. Principles of care management and current knowledge on imaging findings that may affect return to activity are also presented. Using an oriented US examination technique and having knowledge of the normal hip anatomy will help physicians characterize US findings of common sports-related hip injuries and make accurate diagnoses. Online supplemental material is available for this article. ©RSNA, 2018.


Basic skills for successful client relations.
Today's veterinary professional must not only be medically adept but must also possess good communications and client relations skills. Clients are far more likely to judge a practitioner by his or her interpersonal abilities rather than by medical judgment. This chapter stresses the importance of having "a counselor's attitude" toward clients. It will also make clinicians more aware of their verbal and nonverbal communication, hone the ability to listen and empathize, develop the art of questioning and explaining, and teach clinicians to constructively handle anger. These skills will go a long way to enhance relationships, build the practice, and reduce the people-to-people stresses that always arise when a beloved pet's life is compromised, threatened, or ended.


Amine-specificity of the inactivating ornithine decarboxylase modification in Physarum polycephalum.
The enzyme catalysing the polyamine-stimulated modification of Physarum ornithine decarboxylase in vivo was partially purified and its activity on purified ornithine decarboxylase was examined with respect to its specificity for various amines. Spermidine, spermine and several polyamine analogues strongly promoted this reaction in vitro (apparent Km in the 0.1--0.5 mM range), whereas putrescine (apparent Km 5.33 mM) and several related diamines were not nearly as effective. In agreement with this, sensitivity studies performed in vivo also suggested that cellular spermidine, and not putrescine, is critical in modulating ornithine decarboxylase activity by this post-translational control. Unlike putrescine, or other diamines, 1,3-diaminopropane demonstrated a functional similarity to the polyamines in stimulating this reaction. This study has demonstrated a method whereby non-physiological amines capable of depressing ornithine decarboxylase activity by this natural feedback mechanism can be readily identified for further evaluation of their potential use in the experimental and medical control of polyamine biosynthesis.


Nephropathic cystinosis: an update on genetic conditioning.
Cystinosis is an autosomal recessive lysosomal storage disorder caused by CTNS gene mutations. The CTNS gene encodes the protein cystinosin, which transports free cystine from lysosomes to cytoplasm. In cases of cystinosin deficiency, free cystine accumulates in lysosomes and forms toxic crystals that lead to tissue and organ damage. Since CTNS gene mutations were first described, many variations have been identified that vary according to geographic region, although the phenotype remains the same. Cystinosis is a hereditary disease that can be treated with the cystine-depleting agent cysteamine. Cysteamine slows organ deterioration, but cannot treat renal Fanconi syndrome or prevent eventual kidney failure; therefore, novel treatment modalities for cystinosis are of great interest to researchers. The present review aims to highlight the geographic differences in cystinosis-specifically in terms of its genetic aspects, clinical features, management, and long-term complications.


Femicide: Psychosocial Characteristics of the Perpetrators in Turkey.
Female homicides are widely prevalent in Turkey with rising trend. The aim of this study is to identify gender role attitudes, childhood trauma histories, and individual characteristics of men who have been involved in the femicide, and to compare them with men who do not exercise violence against women. Participants completed a Sociodemographic and Clinical Information form, Semistructured Interview form, and the Childhood Trauma Questionnaire. Case group was not significantly different than the control group in terms of any measured individual characteristics including childhood traumas, psychopathology, and gender attitudes. Our data indicate that only migration history may be linked to femicide. A unique psychopathology that could be related to being a femicide perpetrator was not identified. Migration and perception of gender roles stand out as factors that separate men who exercise violence from men who do not.


Exploration of Global Health Careers Across the Medical Fields.
Despite expansion of interest among American medical students in global health (GH), academic medical centers face multiple obstacles to the development of structured GH curricula and career guidance. To meet these demands we sought to provide a systematic analysis of the accounts of GH experts. We developed a collaborative, interview-based, qualitative analysis of GH experiences across six career-related themes that are relevant to medical students interested in GH: justification, medical education, economics, research prospects, law and ethics, and work-life balance. Seven GH faculty members were interviewed for 30-90 minutes using sample questions as guidelines. We applied a grounded theory approach to analyze the interview transcripts to discover an emerging theory pertinent to GH trainees. Regarding justification, 4 respondents defined GH as work with the underserved irrespective of geographic location; 5 respondents found sustainability imperative; and all respondents believe GH creates better physicians. Respondents identified many physician competencies developed through GH medical education, with 5 respondents agreeing that work with underserved populations has transformative potential. Concerning economics, 3 respondents acknowledged GH's popularity among trainees, resulting in increased training opportunities, and 2 respondents emphasized an associated deficiency in program quality. All respondents described career models across specialties. Four respondents noted funding challenges when discussing research prospects. Within the theme of laws and ethics, 4 respondents perceived inadequate accountability, and 6 respondents identified ways to create accountability. Finally, 6 respondents recognized family demands can compromise one's GH career and thus work-life balance. Despite diverse perspectives on the meaning and sustainability of GH work, this analysis provides a nascent framework that may inform curricular development for GH trainees. Suggestions are offered for elaborating this framework to fully exploit the transformative potential of GH training in medical education.


Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly.
Nonalcoholic fatty liver disease (NAFLD) is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been validated to identify high-risk patients. Patients with NAFLD have been shown to have higher serum angiopoietin-like protein-8 (ANGPTL-8) levels. The risk of NAFLD is known insufficiently in acromegaly. Moreover, the utility of the NS and the link between NAFLD and ANGPTL-8 in acromegaly is unknown. Thirty-two patients with acromegaly (n = 15, active [AA] and n = 17, controlled acromegaly [CA]) and 19 healthy controls were included. Magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) was used to evaluate hepatic steatosis, and magnetic resonance elastography to evaluate liver stiffness measurement. ANGPTL-8 levels were measured with ELISA. Median liver MRI-PDFF and NAFLD prevalence in AA were lower than in CA (P = .026 and P < .001, respectively). Median magnetic resonance elastography-liver stiffness measurement were similar across groups. Of the NS, visceral adiposity index, fatty liver index, hepatic steatosis index, and triglyceride-glucose index (TyG) all showed positive correlation with the liver MRI-PDFF in the control group. However, only TyG significantly correlated with liver fat in the AA and CA groups. There was no correlation between traditional NAFLD risk factors (body mass index, waist circumference, C-reactive protein, homeostasis model assessment for insulin resistance, visceral adipose tissue) and liver MRI-PDFF in the AA and CA. Patients with acromegaly with NAFLD had lower GH, IGF-1, and ANGPTL-8 levels than in those without NAFLD (P = .025, P = .011, and P = .036, respectively). Active acromegaly may protect from NAFLD because of high GH. In patients with acromegaly, NAFLD risk cannot be explained with classical risk factors; hence, additional risk factors must be identified. TyG is the best score to evaluate NAFLD risk. Lower ANGPTL-8 in patients with acromegaly and NAFLD implies this hormone may be raised because of insulin resistance rather than being a cause for NAFLD.


The relationship between isolated hypertension with brain volumes in UK Biobank.
Hypertension is a well-established risk factor for cognitive impairment, brain atrophy, and dementia. However, the relationship of other types of hypertensions, such as isolated hypertension on brain health and its comparison to systolic-diastolic hypertension (where systolic and diastolic measures are high), is still relatively unknown. Due to its increased prevalence, it is important to investigate the impact of isolated hypertension to help understand its potential impact on cognitive decline and future dementia risk. In this study, we compared a variety of global brain measures between participants with isolated hypertension to those with normal blood pressure (BP) or systolic-diastolic hypertension using the largest cohort of healthy individuals. Using the UK Biobank cohort, we carried out a cross-sectional study using 29,775 participants (mean age 63 years, 53% female) with BP measurements and brain magnetic resonance imaging (MRI) data. We used linear regression models adjusted for multiple confounders to compare a variety of global, subcortical, and white matter brain measures. We compared participants with either isolated systolic or diastolic hypertension with normotensives and then with participants with systolic-diastolic hypertension. The results showed that participants with isolated systolic or diastolic hypertension taking BP medications had smaller gray matter but larger white matter microstructures and macrostructures compared to normotensives. Isolated systolic hypertensives had larger total gray matter and smaller white matter traits when comparing these regions with participants with systolic-diastolic hypertension. These results provide support to investigate possible preventative strategies that target isolated hypertension as well as systolic-diastolic hypertension to maintain brain health and/or reduce dementia risk earlier in life particularly in white matter regions.


Babesia lengau associated with cerebral and haemolytic babesiosis in two domestic cats.
Although reported sporadically from various countries, feline babesiosis appears to be a significant clinical entity only in South Africa, where Babesia felis is usually incriminated as the causative agent. Babesia lengau, recently described from asymptomatic cheetahs, has now possibly been incriminated as the causative agent in two severe clinical cases in domestic cats. Both cats were euthanised in extremis. While typical feline babesiosis in South Africa is an afebrile disease with a chronic manifestation, there was acute onset of severe clinical signs in both cats and their body temperatures were above the normal range when they were presented for treatment. Haemolytic anaemia was confirmed in one case. To our knowledge, this is the first report of cerebral babesiosis in cats.On reverse line blot 18S rDNA PCR products obtained from both cats showed positive hybridization profiles with the B. lengau species-specific probe. The two partial parasite 18S rRNA gene sequences obtained, showed high sequence similarity (99.9%) to B. lengau. In a representative tree constructed by the neighbor-joining method using the two-parameter model of Kimura the two obtained partial 18S rDNA sequences and that of B. lengau formed a monophyletic group with B. conradae and sequences previously isolated from humans and wildlife in the western USA. All clinical cases of feline babesiosis in South Africa are not necessarily caused by B. felis. Other piroplasms, e.g. B. lengau, may be incriminated in clinical cases, especially those occurring outside the known endemic area.


Serum Paraoxonase, Arylesterase, and Glutathione-S-Transferase Activities and Oxidative Stress Levels in Patients with Mushroom Poisoning.
Consumption of toxic species of mushrooms may have detrimental effects and increase oxidative stress. Paraoxonase, arylesterase and glutathione-S-transferase are antioxidants that resist oxidative stress. In this study, we analyzed the changes in these enzymes during intoxication due to mushrooms. The study enrolled 49 adult patients with a diagnosis of mushroom poisoning according to clinical findings and 49 healthy volunteers as the control group. The patients with mild clinical findings were hospitalized due to the possibility that the patient had also eaten the mushrooms and due to clinical findings in the late period, which could be fatal. Paraoxonase, arylesterase, and glutathione-S-transferase concentrations, as well as total antioxidant and oxidant status, were determined in the 49 patients and 49 healthy volunteers by taking blood samples in the emergency department. While paraoxonase, arylesterase, and total antioxidant status were significantly decreased in the patient group (p<0.05), glutathione-S-transferase, total oxidant status and the oxidative stress index were significantly higher (p<0.05). There was a positive correlation between the hospitalization time and the oxidative stress index (r=0.752, p<0.001), whereas a negative correlation was found with glutathione-S-transferase (r=-0.420, p=0.003). We observed a significant decrease in paraoxonase and arylesterase and an increase in glutathione-S-transferase and oxidative stress indexes in patients with mushroom poisoning, indicating that these patients had an oxidative status. In particular, a low total antioxidant status and high oxidative stress index may gain importance in terms of the assessment of hospitalization duration.


Differences in brain gray matter volume in patients with Crohn's disease with and without abdominal pain.
Increasing evidence indicates that abnormal pain processing is present in the central nervous system of patients with Crohn's disease (CD). The purposes of this study were to assess changes in gray matter (GM) volumes in CD patients in remission and to correlate structural changes in the brain with abdominal pain. We used a 3.0 T magnetic resonance scanner to examine the GM structures in 21 CD patients with abdominal pain, 26 CD patients without abdominal pain, and 30 healthy control subjects (HCs). Voxel-based morphometric analyses were used to assess the brain GM volumes. Patients with abdominal pain exhibited higher CD activity index and lower inflammatory bowel disease questionnaire scores than those of the patients without abdominal pain. Compare to HCs and to patients without abdominal pain, patients with abdominal pain exhibited lower GM volumes in the insula and anterior cingulate cortex (ACC); whereas compare to HCs and to patients with abdominal pain, the patients without abdominal pain exhibited higher GM volumes in the hippocampal and parahippocampal cortex. The GM volumes in the insula and ACC were significantly negatively correlated with daily pain scores. These results suggest that differences exist in the brain GM volume between CD patients in remission with and without abdominal pain. The negative correlation between the GM volumes in the insula and ACC and the presence and severity of abdominal pain in CD suggests these structures are closely related to visceral pain processing.


Quantitative molecular monitoring of BCR-ABL and MDR1 transcripts in patients with chronic myeloid leukemia during Imatinib treatment.
Different mechanisms could sustain Imatinib resistance, including overexpression of MDR1, a gene already known to be responsible for multidrug resistance in other hematologic malignancies. In search for a possible correlation, BCR-ABL and MDR1 expression were measured in 115 serial bone marrow samples from 33 CML patients during Imatinib treatment. All patients achieved complete hematologic responses, and 22 patients also achieved complete cytogenetic responses, with median BCR-ABL mRNA values significantly lower than those observed in the group of cases that were persistently Philadelphia positive. All three cases treated during the accelerated phase showed disease progression after an initial period of remission; all presented either increased levels of BCR-ABL or MDR1 3 months before clinical progression. In the subgroup of cases treated during the chronic phase, BCR-ABL and MDR1 levels were significantly correlated after 3 and 6 months (88 and 80%, respectively) but not after 12 months of treatment (32%). Reported data maintain that MDR1 expression would play an important role in Imatinib resistance when the disease is not fully controlled (e.g., progressive disease or during the first months of treatment).


Broadband light absorption enhancement in polymer photovoltaics using metal nanowall gratings as transparent electrodes.
The authors investigate light absorption in organic solar cells in which indium tin oxide (ITO) is replaced by a new metallic architecture (grating) as a transparent electrode. Different from typical metal nanowire gratings, our gratings consist of metal nanowalls with nanoscale footprint and (sub)microscale height [Adv. Mater. 23, 2469 (2011)], thus ensuring high optical transmittance and electrical conductivity. Simulations reveal that a broadband and polarization-insensitive light absorption enhancement is achieved via two mechanisms, when such silver nanowall gratings are employed in P3HT:PCBM based solar cells. Overall absorption enhanced by ~23% compared to a reference cell with ITO electrode.


The distribution of neuropeptide Y-like immunoreactive neurons in the human medulla oblongata.
We have described the distribution of neuropeptide Y-like immunoreactive neurons in the medulla oblongata of the adult human. The majority of neuropeptide Y-like immunoreactive cells were found in four regions of the medulla: the ventrolateral reticular formation, the dorsomedial medulla, the secondary sensory nuclei and the rostral raphe nuclei. The morphology of neuropeptide Y-like immunoreactive cells varied in each of these regions. In the ventrolateral reticular formation, the labelled neurons were round and pigmented caudal to the obex but elongated and non-pigmented rostral to the obex; in the dorsomedial medulla, they were triangular and pigmented caudal to but not rostral to the obex; in the secondary sensory nuclei, they were multipolar, non-pigmented and significantly smaller than in the other areas; in the rostral raphe nuclei, they were bipolar and non-pigmented. Colocalization studies revealed that many neuropeptide Y-like immunoreactive cells also synthesize monoamines, consistent with conclusions based on a quantitative comparison of their distributions. Neuropeptide Y-like immunoreactivity was present in about 25% of presumed noradrenaline-synthesizing cells in the caudal ventrolateral medulla (corresponding to the A1 region); about 50% of adrenaline- and 70% of presumed serotonin-synthesizing cells in the rostral ventrolateral medulla (C1 and B2-3 regions); 90-100% of presumed noradrenaline-synthesizing cells in the dorsomedial medulla at and above the obex (A2 region); about 50% of adrenaline-synthesizing cells in the rostral dorsomedial medulla (C2 region); about 5% of presumed serotonin-synthesizing cells in the rostral raphe nuclei (B2-3 region). The largest of these groups was the presumed serotonin-synthesizing cells that contained neuropeptide Y-like immunoreactivity in the rostral ventrolateral medulla. This is the first report of such a cell group in the medulla of any mammal, and emphasizes the neuroanatomical differences between humans and other species.


Hemorrhagic complications and repair of congenital diaphragmatic hernias: does timing of the repair make a difference? Data from the Extracorporeal Life Support Organization.
The authors reviewed the Extracorporeal Life Support Organization (ELSO) data base of all neonates placed on extracorporeal membrane oxygenation for whom CDH was diagnosed between January 1989 and December 1991. For 483 neonates, there were complete data concerning timing of the hernia repair in relation to ECMO. The overall incidence of hemorrhage was 43% (57% among nonsurvivors, 32% among survivors; P < .05). The most common bleeding sites were surgical repair site (24%), head (11.5%), cannulation site (7.5%), and gastrointestinal (5%). Fatal hemorrhage occurred in 4.8% (23 of 483). The most common sites of fatal hemorrhage were head (48%), pulmonary (17%), and abdominal (17%). Bleeding complications were significantly greater for patients repaired on ECMO (58%) versus those repaired before (37%) or after (21%) (P < .05). Surgical-site hemorrhage requiring transfusion occurred in 38% of those repaired on ECMO versus 18% and 6% of those repaired before and after, respectively (P < .05). Gastrointestinal and "other" sites of hemorrhage were significantly more common in those repaired on bypass. The number of patients repaired on ECMO increased from 22% to 48% over the 3 years (P < .05). The incidence of hemorrhagic complications did not differ significantly among the 3 years (P > .05). Repair of the hernia defect while on bypass was associated with significantly greater bleeding complications. These data should be useful in the planning of future prospective trials.


Review of shaken baby syndrome.
1. Shaken baby syndrome can lead to substantial neuropsychological deficits that can alter children's normal developmental course. 2. Clinical acumen can be critical in identifying shaken baby syndrome and preventing further difficulties. 3. Education and treatment for caregivers can be important in reducing the likelihood of shaken baby syndrome.


[Correction with T-activin of secondary immunodeficiency in inflammatory diseases of female internal genital organs].
A clinicoimmunological examination was performed in 70 patients with acute inflammatory disease of internal genitalia. All the patients received a multimodality anti-inflammatory therapy. They were divided into 2 groups: 1) 30 patients taking ++T-activin as an adjuvant and 2) 40 patients untreated with it. T and B lymphocytes were measured by current cytofluorometry+ by means of monoclonal antibodies and the rosette-forming method. A subpopulation analysis of the T-cell immune system revealed lower T-helper count and decreased immunoregulatory index. ++T-activin used in the multimodality therapy for acute inflammatory diseases of internal genitalia improved the qualitative parameters of regulatory T-cell subpopulations, returned T and B lymphocytes to normal levels and elevated IgG concentrations.


[The microenvironment of tumor cells and the antitumor effect of hyperthermia].
Intravenous infusion of 20% solution of glucose (80 mg/kg of body mass per 1 min) resulted in considerable changes in microenvironment of tumor cells: by the 90th-120th min of infusion there was a decrease in pH, pO2, blood flow inhibition, an increase in the relative number of cells in the S-phase of the mitotic cycle in a tumor. There was no increase in tumor ATP and glucose up to the values at which these substance could enhance thermoresistance, a situation being rather favorable for realizing a damaging effect of hyperthermia. The use of hyperglycemia in the above regimen prior to MWF-hyperthermia enhanced 2-3 times its antitumor effect on the model of subcutaneously transplanted Guéren carcinoma and Pliss lymphosarcoma. Glucose at the concentration of 5-0 mmol enhanced the thermosensitivity of L-1210 cells. The results indicated the efficacy of hyperglycemia combined with hyperthermia.


Magic pairs and structural transitions in binary metallic clusters.
Structures and binding energies for bimetallic clusters consisting of a large variety of atomic species are obtained for all atomic sizes N≤40 and all concentrations, using an interatomic potential derived within a quasi-classical description. It is found that increasing the difference between the two types of atoms leads to a gradual disappearance of the well-known homo-atomic geometric magic numbers and the appearance of magic pairs corresponding to the number of atoms of each atomic species in binary nanostructures with higher stability. This change is accompanied by structural transitions and ground-state↔isomer inversions, induced by changes in composition or concentration. There is a clear tendency towards phase separation, the core-shell radial segregation being predominant (energetically favored) in this model.


Predicting hydration layers on surfaces using deep learning.
Characterisation of the nanoscale interface formed between minerals and water is essential to the understanding of natural processes, such as biomineralization, and to develop new technologies where function is dominated by the mineral-water interface. Atomic force microscopy offers the potential to characterize solid-liquid interfaces in high-resolution, with several experimental and theoretical studies offering molecular scale resolution by linking measurements directly to water density on the surface. However, the theoretical techniques used to interpret such results are computationally intensive and development of the approach has been limited by interpretation challenges. In this work, we develop a deep learning architecture to learn the solid-liquid interface of polymorphs of calcium carbonate, allowing for the rapid predictions of density profiles with reasonable accuracy.


Transforming growth factor beta modulates gonadotropin receptor expression in porcine and rat granulosa cells differently.
Almost without exception, the studies to date describing the effects of transforming growth factor beta (TGF beta) upon various ovarian cell types have utilized the subtype TGF beta 1. Since TGF beta 1 and TGF beta 2 have been demonstrated to influence major developmental processes differentially during hematopoiesis and embryogenesis, we investigated in two species (rat and pig) whether they might also differentially modulate principal regulatory processes of ovarian cellular differentiation, specifically FSH and/or LH receptor (FSHR, LHR) expression. TGF beta 1 plus FSH significantly stimulated LHR binding levels by cultured granulosa cells (GC) from prepubertal diethylstilbestrol-treated rats. TGF beta 2 produced the same effect. In porcine GC from 1-3-mm antral follicles, TGF beta 1 and TGF beta 2 again acted similarly, but the direction of the response was opposite to that in the rat GC system. This difference could not be ascribed to the fact that the GC utilized represented different stages of follicular development in vivo because TGF beta 1 also potentiated FSH-dependent LHR induction in GC from antral follicles of cycling rats at all stages of the estrous cycle. The major effect of TGF beta 1 on FSHR expression in the rat system was to increase binding by attenuating the down-regulatory action of cholera toxin (CTX) or FSH. In the porcine system, TGF beta reduced FSHR binding at FSH or CTX concentrations that enhanced expression, and it did not attenuate the down-regulatory effect of FSH or CTX at higher doses. In summary, TGF beta up- or down-regulated LHR and FSHR binding coordinately within species.(ABSTRACT TRUNCATED AT 250 WORDS)


Surgery for treating hip impingement (femoroacetabular impingement).
Surgery is sometimes recommended for femoroacetabular impingement where non-operative interventions have failed. To determine the benefits and safety of surgery for femoroacetabular impingement. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11); MEDLINE (Ovid) (1946 to 19 November 2013); and EMBASE (Ovid) (1980 to 19 November 2013) for studies, unrestricted by language. Randomised and quasi-randomised clinical trials assessing surgical intervention compared with placebo treatment, non-operative treatment or no treatment in adults with femoroacetabular impingement. Two authors independently selected trials for inclusion, assessed risk of bias and extracted data. There were no studies that met the inclusion criteria, with 11 studies that were excluded following detailed review. There were four ongoing studies identified that may meet the inclusion criteria when they are completed; the results from these ongoing studies may begin to become available within the next five years. Three of the four ongoing studies are comparing hip arthroscopy versus non-operative care. The fourth study is comparing hip arthroscopy versus a sham arthroscopic hip procedure. All of the ongoing studies are recording at least one of our preferred clinical outcome measures for benefit and safety. There is no high quality evidence examining the effectiveness of surgery for femoroacetabular impingement. There are four ongoing studies, which may provide evidence for the benefit and safety of this type of surgery in the future.


Scaling behavior of electronic excitations in assemblies of molecules with degenerate ground states.
The behavior of long space-time excitations in many-electron systems with ground state degeneracy is explored via multiscale analysis. The analysis starts with an ansatz for the wave function's dual dependence on the N-electron configuration (i.e., both by direct means and by indirect means via a set of order parameters). It is shown that a Dirac-like equation form of the wave equation emerges in the limit where the ratio epsilon (of the average nearest-neighbor distance to the characteristic length of the long-scale phenomenon of interest) is small. Examples of the long scale are the size of a quantum dot, nanotube, or wavelength of a density disturbance. The velocities in the Dirac-like equation are the transition moments of the single-particle momentum operator connecting degenerate ground states. While detailed band structure and the independent quasi-particle picture could underlie the behavior of some systems (as commonly suggested for graphene), the present scaling law results show it is not necessarily the only explanation. Rather, it can follow from the scaling properties of low-lying, long spatial scale excitations and ground state degeneracy, even in strongly interacting systems. The generality of our findings suggests graphene may be just one of many examples of Dirac-like equation behavior. A preliminary validation of our quantum scaling law for molecular arrays is presented. As our scaling law constitutes a coarse-grained wave equation, path integral or other methods derived from it hold great promise for calibration-free, long-time simulation of many-particle quantum systems.


Teaching personal awareness.
Educators rarely consider the attitudes that determine whether a learner will use the clinical skills we teach. Nevertheless, many learners and practitioners exhibit negative attitudes that can impede the use of patient-centered skills, leading to an isolated focus upon disease and impairing the provider-patient relationship. The problem is compounded because these attitudes often are incompletely recognized by learners and therefore are difficult to change without help. We present a research-based method for teaching personal awareness of unrecognized and often harmful attitudes. We propose that primary care clinicians without mental health training can follow this method to teach students, residents, faculty, and practitioners. Such teachers/mentors need to possess an abiding interest in the personal dimension, patience with a slowly evolving process of awareness, and the ability to establish strong, ongoing relationships with learners. Personal awareness teaching may occur during instruction in basic interviewing skills but works best if systematically incorporated throughout training.


Short communication: Evaluation of acid-insoluble ash and indigestible neutral detergent fiber as total-tract digestibility markers in dairy cows fed corn silage-based diets.
The objective of this experiment was to evaluate acid-insoluble ash (AIA) and indigestible NDF (iNDF) as intrinsic digestibility markers in comparison with total fecal collection (TC) in dairy cows fed corn silage- and alfalfa haylage-based diets. The experiment was part of a larger experiment, which involved 8 Holstein cows [102±28.4 d in milk, 26.4±0.27 kg/d of dry matter (DM) intake, and 43±5.3 kg/d milk yield]. The experimental design was a replicated 4×4 Latin square with the following treatments: metabolizable protein (MP)-adequate diet [15.6% crude protein (CP); high-CP], MP-deficient diet (14.0% CP; low-CP), and 2 other low-CP diets supplemented (top-dressed) with ruminally protected Lys or Lys and Met. Data for the 3 low-CP diets were combined for this analysis. Total feces were collected for 5 consecutive days during each period to estimate total-tract apparent digestibility. Digestibility was also estimated using AIA (digestion with 2 N HCl) and iNDF (12-d ruminal incubation in 25-μm-pore-size bags). Significant diet × digestibility method interactions were observed for fecal output of nutrients and digestibility. Fecal output of nutrients estimated using AIA or iNDF was lower compared with TC and fecal output of DM, organic matter, and CP tended to be higher for iNDF compared with AIA for the high-CP diet. For the low-CP diet, however, fecal output of all nutrients was lower for AIA compared with TC and was higher for iNDF compared with TC. Data from this experiment showed that, compared with TC, AIA underestimated fecal output and overestimated digestibility, particularly evident with the fiber fractions and the protein-deficient diet. Compared with TC, fecal output was overestimated and digestibility of the low-CP diet was underestimated when iNDF was used as a marker, although the magnitude of the difference was smaller compared with that for AIA. In the conditions of the current study, iNDF appeared to be a more reliable digestibility marker than AIA in terms of detecting dietary differences in apparent digestibility of some nutrients, but significant diet × marker interactions existed that need to be considered when estimating total-tract digestibility using intrinsic markers.


A structural UGDH variant associated with standard Munchkin cats.
Munchkin cats were founded on a naturally occurring mutation segregating into long-legged and short-legged types. Short-legged cats showed disproportionate dwarfism (chondrodysplasia) in which all four legs are short and are referred as standard Munchkin cats. Long-legged animals are referred as non-standard Munchkin cats. A previous study using genome-wide single nucleotide polymorphisms (SNPs) for genome-wide association analysis identified a significantly associated region at 168-184 Mb on feline chromosome (FCA) B1. In this study, we validated the critical region on FCA B1 using a case-control study with 89 cats and 14 FCA B1-SNPs. A structural variant within UGDH (NC_018726.2:g.173294289_173297592delins108, Felis catus 8.0, equivalent to NC_018726.3:g.174882895_174886198delins108, Felis catus 9.0) on FCA B1 was perfectly associated with the phenotype of short-legged standard Munchkin cats. This UGDH structural variant very likely causes the chondrodysplastic (standard) phenotype in Munchkin cats. The lack of homozygous mutant phenotypes and reduced litter sizes in standard Munchkin cats suggest an autosomal recessive lethal trait in the homozygote state. We propose an autosomal dominant mode of inheritance for the chondrodysplastic condition in Munchkin cats.


A role for lymphocytes and cytokines on the eosinophil migration induced by LPS.
In the present work we review the existing evidence for a LPS-induced cytokine-mediated eosinophil accumulation in a model of acute inflammation. Intrathoracic administration of LPS into rodents (mice, rats or guinea pigs) induces a significant increase in the number of eosinophils recovered from the pleural fluid 24 hr later. This phenomenon is preceded by a neutrophil influx and accompanied by lymphocyte and monocyte accumulation. The eosinophil accumulation induced by LPs is not affected by inhibitors of cyclo or lipoxygenase nor by PAF antagonists but can be blocked by dexamethasone or the protein synthesis inhibitor cycloheximide. Transfer of cell-free pleural wash from LPS injected rats (LPS-PW) to naive recipient animals induces a selective eosinophil accumulation within 24 hr. The eosinophilotactic activity present on the LPS-PW has a molecular weight ranging between 10 and 50 kDa and its effect is abolished by trypsin digestion of the pleural wash indicating the proteic nature of this activity. The production of the eosinophilotactic activity depends on the interaction between macrophages and T-lymphocytes and its effect can not be blocked by anti-IL-5 monoclonal antibodies. Accumulated evidence suggest that the eosinophil accumulation induced by LPS is a consequence of a eosinophilotactic cytokine produced through macrophage and T-cell interactions in the site of a LPS-induced inflammatory reaction.


[The treatment of salmonellosis in children].
The time course of salmonellosis and some immunity indices (composition of serum immunoglobulins A, M and G, phagocytosis and activity of bactericidal substances of peripheral blood neutrophils) were studied in 80 infants. According to the applied therapy the infants were divided into 2 groups. 40 infants of group 1 were subjected to the routine therapy with gentamicin and tobramycin and 40 patients of group 2 were additionally treated with an immunostimulant (humisol). In the patients of group 2 treated with the antibiotics and humisol the disease time course was more favourable, the time required for the treatment was shorter and the hemograms and immunity indices earlier came to the normal.


Compressed sensorimotor-to-transmodal hierarchical organization in schizophrenia.
Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal-parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory-motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.


Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation.
Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful as an unconditioned stimulus for modelling anticipatory fear and agoraphobia in a contextual fear conditioning paradigm. In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then attempted to unravel some of the interactions with dopamine signalling using tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons. We showed that acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, while chronic administrations of both drugs were effective. We found that the dlPAG stimulation induced increase number of dopaminergic neurons in the ventral tegmental area (VTA) which was reversed in both chronic buspirone and escitalopram groups. We further found a strong positive correlation between the number of dopaminergic neurons and freezing in the VTA and showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta (SNpc) in escitalopram and buspirone groups, respectively. Overall, we showed that chronic treatment with an SSRI and a 5-HT1A agonist reduced anticipatory freezing behaviour which seems to be associated, through correlative studies, with a reversal of dlPAG stimulation induced increase in number of dopaminergic neurons in the VTA and/or SNpc.


The Mucosal and Serological Immune Responses to the Novel Coronavirus (SARS-CoV-2) Vaccines.
Although the serological antibody responses induced by SARS-CoV-2 vaccines are well characterized, little is known about their ability to elicit mucosal immunity. This study aims to examine and compare the mucosal and systemic responses of recipients of two different vaccination platforms: mRNA (Comirnaty) and inactivated virus (CoronaVac). Serial blood and nasal epithelial lining fluid (NELF) samples were collected from the recipients of either Comirnaty or CoronaVac. The plasma and NELF immunoglobulins A and G (IgA and IgG) specific to SARS-CoV-2 S1 protein (S1) and their neutralization effects were quantified. Comirnaty induced nasal S1-specific immunoglobulin responses, which were evident as early as 14 ± 2 days after the first dose. In 64% of the subjects, the neutralizing effects of NELF persisted for at least 50 days. Moreover, 85% of Comirnaty recipients exhibited S1-specific IgA and IgG responses in plasma by 14 ± 2 days after the first dose. By 7 ± 2 days after the booster, all plasma samples possessed S1-specific IgA and IgG responses and were neutralizing. The induction of S1-specific plasma antibodies by CoronaVac was IgG dominant, and 83% of the subjects possessed S1-specific IgG by 7 ± 2 days after the booster, with neutralizing effects. Comirnaty induces S1-specific IgA and IgG responses with neutralizing activity in the nasal mucosa; a similar response is not seen with CoronaVac. The presence of a nasal response with mRNA vaccine may provide additional protection compared with inactivated virus vaccine. However, whether such widespread immunological response may produce inadvertent adverse effects in other tissues warrants further investigation.


Lamivudine in the treatment of HBV-related liver disease after renal transplantation: an update.
Diminished survival due to hepatitis B has been observed after renal transplantation (RT). Lamivudine, a second-generation nucleoside analogue, has been approved for the treatment of chronic hepatitis B virus (HBV) infection in patients with normal renal function. Numerous clinical experiences with lamivudine after RT have been recently published. Despite numerous shortcomings, all of these reports have shown encouraging results. The rate of clearance of HBV viremia ranged between 67% and 100%, and the frequency of ALT normalization was between 50% and 100% with lamivudine use. Even patients with fibrosing cholestatic hepatitis, a serious form of HBV-related liver disease with ominous course, have been successfully treated with lamivudine. Lamivudine therapy significantly improved the survival of HBsAg positive renal allograft recipients. However, numerous issues concerning the treatment of hepatitis B after RT remain unclear: the optimal time to initiate lamivudine, the appropriate duration of antiviral therapy after RT, and the role for pre-transplantation liver biopsy. Also, the management of lamivudine resistance remains a concern for physicians. Clinical trials are under way.


Targeting autophagy in cancer management - strategies and developments.
Autophagy is a highly regulated catabolic process involving lysosomal degradation of intracellular components, damaged organelles, misfolded proteins, and toxic aggregates, reducing oxidative stress and protecting cells from damage. The process is also induced in response to various conditions, including nutrient deprivation, metabolic stress, hypoxia, anticancer therapeutics, and radiation therapy to adapt cellular conditions for survival. Autophagy can function as a tumor suppressor mechanism in normal cells and dysregulation of this process (ie, monoallelic Beclin-1 deletion) may lead to malignant transformation and carcinogenesis. In tumors, autophagy is thought to promote tumor growth and progression by helping cells to adapt and survive in metabolically-challenged and harsh tumor microenvironments (ie, hypoxia and acidity). Recent in vitro and in vivo studies in preclinical models suggested that modulation of autophagy can be used as a therapeutic modality to enhance the efficacy of conventional therapies, including chemo and radiation therapy. Currently, more than 30 clinical trials are investigating the effects of autophagy inhibition in combination with cytotoxic chemotherapies and targeted agents in various cancers. In this review, we will discuss the role, molecular mechanism, and regulation of autophagy, while targeting this process as a novel therapeutic modality, in various cancers.


RNA-RNA in situ hybridization using digoxigenin-labeled probes: the use of high-molecular-weight polyvinyl alcohol in the alkaline phosphatase indoxyl-nitroblue tetrazolium reaction.
A nonradioactive RNA-RNA in situ hybridization method using digoxigenin-labeled probes is described. The visualization of hybrids is done using the indoxyl-nitro blue tetrazolium alkaline phosphatase reaction. The addition of polyvinyl alcohols of high molecular weight (40-100 kDa) to the reaction medium enhances the alkaline phosphatase reaction and prevents diffusion of reaction intermediates, resulting in a 20-fold increase in sensitivity without increasing the background. Due to the more localized precipitation of the formazan, the site of hybridization can be determined more precisely.


Atrial fibrillation in low- and middle-income countries: a narrative review.
Preventing premature non-communicable disease mortality necessitates a thorough review of one of the most important risk factors for stroke, which is atrial fibrillation (AF). The latter and AF-related stroke are still considered to be problems of high-income countries and are frequently overlooked in low- and middle-income countries (LMICs). In this narrative review, we provide an overview of studies that evaluated at least one of the following determinants of AF burden in LMICs: current epidemiology and trends, stroke prevention, health outcomes, and economic burden. Studies focusing on samples close to the general population (including community- and primary care-based samples) indicate sex-specific prevalence rates up to 7.4% in LMICs. Although AF prevalence is still higher in high-income countries than LMICs, the gap in AF burden between these two groups has been reducing in the past three decades. Oral anticoagulant (OAC) therapy for stroke prevention is underused in LMICs, and there are little data on OAC therapy in relation to stroke risk scores, such as CHA2DS2-VASc. Available data also points to higher morbidity and mortality for patient with AF in LMICs than their counterparts in high-income countries. Data on the consequent economic burden in LMICs is scarce, but it is reasonable to consider it will follow the same trend as that observed for health outcomes. Raising the visibility of AF as a public health problem in LMICs is necessary as a first step to providing adequate care for patients with this condition.


Reconstruction of the nigrostriatal dopamine pathway in the adult mouse brain.
Transplants of fetal dopamine neurons can be used to restore dopamine neurotransmission in animal models of Parkinson's disease, as well as in patients with advanced Parkinson's disease. In these studies the cells are placed in the striatum rather than in the substantia nigra where they normally reside, which may limit their ability to achieve full restoration of motor function. Using a microtransplantation approach, which allows precise placement of small cell deposits directly into the host substantia nigra, and fetal donor cells that express green fluorescent protein under the control of the tyrosine hydroxylase promoter, we show that dopamine neuroblasts implanted into the substantia nigra of adult mice are capable of generating a new nigrostriatal pathway with an outgrowth pattern that matches the anatomy of the intrinsic system. This target-directed regrowth was closely aligned with the intrinsic striatonigral fibre projection and further enhanced by over-expression of glial cell line-derived neurotrophic factor in the striatal target. Results from testing of amphetamine-induced rotational behaviour suggest, moreover, that dopamine neurons implanted into the substantia nigra are also capable of integrating into the host circuitry at the functional level.


Non-resident orthopaedic admissions to Dunedin Hospital, New Zealand: 1997 to 2004.
The purpose of this study is to audit the numbers of non-residents requiring orthopaedic admission to our hospital and determine the effect of increasing tourist numbers and changes in Accident ACC regulations on healthcare resources. Details of non-resident orthopaedic admissions for fiscal years 1997/8 to 2003/4 were analysed with respect to country of residence, mechanism of injury, case weights consumed, and actual costs. There has been no change in numbers of admissions or cost, averaging 32 cases (50 case weights [CWs]) per year. Most patients came from Asia (59 cases; 26%), then Australia (52 cases; 23%) and UK (40 cases; 18%). Snowsports accounted for 40% of admissions, Motor vehicle accidents (MVA) for 17%, and falls for 29%. Non-resident, non-MVA admissions have averaged 21 CWs per year since the changes in ACC regulations in 1999. Despite increasing tourist numbers, there has been no increase in numbers or CW of non-residents requiring orthopaedic admission. Although representing only a small proportion of the orthopaedic budget, they generate many hidden costs. The 50 CWs annually equates to approximately 13 major joint replacements per year. The increase in CWs consumed due to the ACC changes have had no corresponding increase in contracted orthopaedic volumes.


An outbreak of Q fever in the Basque country.
The main clinical manifestations of 42 cases of Q fever occurring in an outbreak in Valmaseda, Spain during March, April and May 1982 are described in this paper. The benign character of the acute disease is emphasized. Further epidemiologic studies must be done to determine the incidence of Q fever in the Basque country.


Size at birth, infant, early and later childhood growth and adult body composition: a prospective study in a stunted population.
Pre-natal and post-natal growth are associated with adult body composition, but the relative importance of growth in different periods of childhood is still unclear, particularly in stunted populations. We studied 358 women and 352 men measured as children in 1969-77 in four villages in Guatemala, and re-measured as adults in 2002-04 (mean age 32.7 years). We determined the associations of body mass index (BMI) and length at birth, and changes in BMI and length during infancy (0-1.0 year) and early (1.0-3.0 years) and later (3.0-7.0 years) childhood, with adult BMI ((a)BMI), percentage of body fat ((a)PBF), abdominal circumference ((a)AC) and fat-free mass ((a)FFM). Prevalence of stunting was high (64% at 3 years; HAZ < -2SD). Obesity (WHZ > 2SD) prevalence in childhood was <2%, while overweight prevalence in adulthood was 52%. BMI at birth was positively associated with (a)BMI and (a)FFM while length at birth was positively associated with (a)AC and (a)FFM. Increased BMI in infancy and later childhood were positively associated with all four adult body composition measures; associations in later childhood with fatness and abdominal fatness were stronger than those with (a)FFM. Change in length during infancy and early childhood was positively associated with all four adult body composition outcomes; the associations with (a)FFM were stronger than those with fat mass. Increases in BMI between 3.0 and 7.0 years had stronger associations with adult fat mass and abdominal fat than with (a)FFM; increases in length prior to age 3.0 years were most strongly associated with increases in (a)FFM.


Risk of trauma exposure among persons with mental illness in jails and prisons: what do we really know?
Traumatic victimization, particularly sexual abuse, is a serious problem in correctional facilities and those suffering from mental illnesses are especially vulnerable. This review examines our current knowledge regarding trauma victimization among persons with mental illness serving time in jails/prisons, considers methodological challenges, and provides recommendations for future research. Traumatic victimization, particularly sexual abuse, has consistently been identified as a high-frequency problem within jails and prisons. Lifetime, 6-month, and 12-month prevalence rates of physical and sexual violence among incarcerated people are quite high relative to nonincarcerated populations, and women report much higher rates of most traumatic events than men. Moreover, data show that inmates with mental illnesses are up to eight times more likely to be victims of sexual abuse than nonmentally ill inmates. Additional research is needed to improve our understanding of this issue and inform change efforts. Future research should include: epidemiological studies to improve our knowledge of risk factors and correlates of victimization; prospective studies to determine causality between trauma victimization and mental illness or other adverse outcome; and intervention studies to examine strategies for reducing violence and traumatic victimization inside correctional facilities, effective treatments for posttraumatic psychopathology, and improved re-entry outcomes.


Marginal Bone Level Evaluation of Fixed Partial Dental Prostheses Using Preformed Stock versus CAD/CAM Customized Abutments.
Background: The maintenance of marginal bone levels around dental implants is an important criterion for evaluating the success of implants. Although computer-aided design/computer-aided manufacturing (CAD/CAM) customized abutments (CAs) provide more flexible solutions, compared with the original preformed stock abutments (PAs), there are dimensional tolerances and underlying drawbacks in the production of CAD/CAM CAs, which may change the tightness and seamless connection between fixtures and abutments set by the manufacturer and then affect the long-term stability of the abutments. This study aimed to examine the change in both mesial and distal bone levels using digital periapical radiographs to evaluate the difference between CAD/CAM CAs and original PAs.Material and methods: Radiographs were taken before delivery; after functional loading for 1 month; and after 3, 6, and 12 months; and the vertical marginal bone levels (vMBLs) of both the mesial and distal surrounding implant bones were measured. All data are presented as means ± standard errors and were analyzed using Student's t-test. A p-value < 0.05 was judged to represent a significant difference. Results: A total of 57 implants in 50 patients were divided into 22 CAD/CAM CAs and 35 original stock abutments. The PAs appeared to have a more stable bone level. By contrast, the amount of bone level change in the CAs was higher than that in the PAs. The change in the vMBL of the CAs was significantly more than that of the PAs after functional loading for 1 month (p = 0.006), 3 months (p = 0.013), 6 months (p = 0.014), and 12 months (p = 0.002). In contrast, the distal marginal bone level was lower than the mesial marginal bone level in any period. Nevertheless, the bone levels of the CAs and PAs in any period were comparable with no significant difference. Conclusions: Significant differences were found between the mesial and distal bone levels in the PAs. The CAD/CAM CAs showed a significantly greater bone level change than the original stock abutments after functional loading.


[Diurnal rhythm of physiologic functions in workers exposed to noise].
To reveal the mechanisms of adaptation to occupational factors, the authors screened the workers exposed to noise for changes of pulse rate, blood pressure, catecholamines content, auditory threshold within a day. The study showed that adaptation to unfavorable work conditions deteriorates within a day (from morning to night shifts). Reliability of catecholamines level was conditioned by the night fall of catecholamines level and its changes within a day. Compromised adaptation to chronic unfavorable occupational factors result in unstable catecholamines level. Functional state of hearing is mediated by vegetative state including catecholamines content.


Nutritional metabolomics in critical illness.
Disruption of metabolic homeostasis is universal in the critically ill. Macronutrients and micronutrients are major environmental regulators of metabolite production through their gene regulation effects. The study of large numbers of circulating metabolites is beginning to emerge through the comprehensive profiling of the critically ill. In the critically ill, metabolomic studies consistently show that changes in fatty acids, lipids and tryptophan metabolite pathways are common and are associated with disease state and outcomes. Metabolomics is now being applied in research studies to determine the critical illness response to nutrient deficiency and delivery. Nutritional metabolomics approaches in nutrient deficiency, malnutrition and nutrient delivery have included single time point studies and dynamic studies of critically ill patients over time. Integration of metabolomics and clinical outcome data may create a more complete understanding of the control of metabolism in critical illness. The integration of metabolomic profiling with transcription and genomic data may allow for a unique window into the mechanism of how nutrient deficiency and delivery alters cellular homeostasis during critical illness and modulates the regain of cellular homeostasis during recovery. The progress and the challenges of the study of nutritional metabolomics are reviewed here.


Nevasic audio program for the prevention of chemotherapy induced nausea and vomiting: A feasibility study using a randomized controlled trial design.
Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting (CINV). Therefore, exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important. Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction. The aim of this study was to examine the feasibility of conducting a randomized controlled trial (RCT) to evaluate the effectiveness of Nevasic to control CINV. A mixed methods design incorporating an RCT and focus group interviews. For the RCT, female breast cancer patients were randomized to receive either Nevasic plus usual care, music plus usual care, or usual care only. Data were analysed using descriptive statistics and linear mixed-effects models. Five focus group interviews were conducted to obtain participants' views regarding the acceptability of the interventions in the trial. 99 participants were recruited to the RCT and 15 participated in focus group interviews. Recruitment targets were achieved. Issues of Nevasic acceptability were highlighted as weaknesses of the program. This study did not detect any evidence for the effectiveness of Nevasic; however, the results showed statistically significant less use of anti-emetics (p = 0.003) and borderline non-significant improvement in quality of life (p = 0.06). Conducting a non-pharmacological intervention using such an audio program is feasible, although difficulties and limitations exist with its use. Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use, as well as its overall effect on the levels of nausea and vomiting.


Contrast agent stability: a continuous B-mode imaging approach.
The stability of contrast agents in suspensions with various dissolved gas levels has not been reported in the literature. An in vitro investigation has been carried out that studied the combined effect of varying the acoustic pressure along with degassing the suspension environment. In this study, the contrast agents were introduced into suspensions with different oxygen concentration levels, and their relative performance was assessed in terms of decay rate of their backscatter echoes. The partial pressures of oxygen in those solutions ranged between 1.5 and 26 kPa. Two IV and one arterial contrast agents were used: Definity, Quantison, and Myomap. It was found that Quantison and Myomap released free bubbles at high acoustic pressure that also dissolved faster in degassed suspensions. The backscatter decay for Definity did not depend on the air content of the suspensions. The destruction of bubbles was dependent on acoustic pressure. Different backscatter performance was observed by different populations of bubbles of the last two agents. The physical quantity of "overall backscatter" (OB) was defined as the integral of the decay rate over time of the backscatter of the contrast suspensions, and improved significantly the understanding of the behaviour of the agents. A quantitative analysis of the backscatter properties of contrast agents using a continuous imaging approach was difficult to achieve. This is due to the fact that the backscatter in the field of view is representative of a bubble population affected by the ultrasound (US) field, but this bubble population is not representative of the contrast suspension in the whole tank. Single frame insonation is suggested to avoid the effects of decay due to the ultrasonic field, and to measure a tank-representative backscatter. The definition of OB was useful, however, in understanding the behaviour of the agents.


Primary mediastinal paraganglioma associated with a familial variant in the succinate dehydrogenase B subunit gene.
Surgical management is the mainstay of therapy for primary cardiac tumors, yet due to the rarity of these malignancies, their management and workup remains a challenge. Here, we report a unique case of a patient with a primary left ventricular cardiac paraganglioma (PGL) and describe the role of a medical genetics assessment leading to the identification of a rare variant in the SDHB gene to be the causative etiology of this cardiac tumor. Due to decreasing costs and accessibility of molecular genetic analysis, genetic testing may become an emerging diagnostic adjunct in cases of cardiac tumors.


A genetic polymorphism in P2RY1 impacts response to clopidogrel in cats with hypertrophic cardiomyopathy.
Clopidogrel is converted to its active metabolite by cytochrome P450 isoenzymes and irreversibly inhibits platelet activation by antagonizing the adenosine-diphosphate (ADP) receptor. It is frequently used in cats with hypertrophic cardiomyopathy (HCM) to prevent thromboembolic complications. However, significant interpatient variability of the response to clopidogrel therapy has been suspected. In this study, we assessed the impact of single nucleotide polymorphisms (SNPs) within ADP receptor (P2RY1, P2RY12) and cytochrome P450 isoenzyme (CYP2C41) genes on platelet inhibition by clopidogrel administration in cats with HCM. Forty-nine cats completed the study, and blood samples were obtained before and after clopidogrel therapy to assess the degree of platelet inhibition based on flow cytometry and whole blood platelet aggregometry. Plasma concentrations of clopidogrel metabolites were measured after the last dose of clopidogrel. Whole blood platelet aggregometry revealed a significant reduction of platelet inhibition by clopidogrel in cats with the P2RY1:A236G and the P2RY12:V34I variants. The association with the P2RY1:A236G variant and clopidogrel resistance remained significant after adjustment for multiple comparisons. This study demonstrated that a genetic polymorphism in the P2RY1 gene altered response to clopidogrel therapy and suggests that clinicians may consider alternative or additional thromboprophylactic therapy in cats with the P2RY1:A236G variant.


Nerve growth factor-dependence of herpes simplex virus latency in peripheral sympathetic and sensory neurons in vitro.
Previously, we reported that nerve growth factor (NGF) is required to maintain herpes simplex virus (HSV) latency in cultures of rat sympathetic neurons (Wilcox and Johnson, 1987, 1988). Here, we extend these results by showing that NGF was also required to maintain HSV latency in cultures of sensory neurons obtained from dorsal root ganglia of rats, monkeys, and humans. The interruption of the neuronal supply of NGF for 1 hr reactivated HSV, indicating that the latent virus was exquisitely sensitive to perturbations in the concentration or binding of NGF. A species-specific monoclonal antibody directed against the human NGF-receptor, which blocks NGF binding, reactivated latent HSV in human, but not rat, sensory neurons. In contrast, a monoclonal antibody against the rat NGF-receptor, which binds the receptor without blocking NGF action, did not produce reactivation. These results indicate that the effects of NGF on HSV latency are mediated via NGF binding to the NGF receptor. In addition, treatments that interfere with specific steps in the transduction of the NGF signal, including treatment with 6-hydroxydopamine and colchicine, reactivated latent HSV. Further, in neurons harboring latent virus, interruption of protein synthesis or RNA transcription for 1 hr resulted in viral reactivation, suggesting that a short-lived factor may be present in neurons which represses viral reactivation.


CCL2 protects prostate cancer PC3 cells from autophagic death via phosphatidylinositol 3-kinase/AKT-dependent survivin up-regulation.
Resistance to cell death is a hallmark of cancer. Autophagy is a survival mechanism activated in response to nutrient deprivation; however, excessive autophagy will ultimately induce cell death in a nonapoptotic manner. The present study demonstrates that CCL2 protects prostate cancer PC3 cells from autophagic death, allowing prolonged survival in serum-free conditions. Upon serum starvation, CCL2 induced survivin up-regulation in PC3, DU 145, and C4-2B prostate cancer cells. Both cell survival and survivin expression were stunted in CCL2-stimulated PC3 cells when treated either with the phosphatidylinositol 3-kinase inhibitor LY294002 (2 microm) or the Akt-specific inhibitor-X (Akti-X; 2.5 microm). Furthermore, CCL2 significantly reduced light chain 3-II (LC3-II) in serum-starved PC3; in contrast, treatment with LY294002 or Akti-X reversed the effect of CCL2 on LC3-II levels, suggesting that CCL2 signaling limits autophagy in these cells. Upon serum deprivation, the analysis of LC3 localization by immunofluorescence revealed a remarkable reduction in LC3 punctate after CCL2 stimulation. CCL2 treatment also resulted in a higher sustained mTORC1 activity as measured by an increase in phospho-p70S6 kinase (Thr389). Rapamycin, an inducer of autophagy, both down-regulated survivin and decreased PC3 cell viability in serum-deprived conditions. Treatment with CCL2, however, allowed cells to partially resist rapamycin-induced death, which correlated with survivin protein levels. In two stable transfectants expressing survivin-specific short hairpin RNA, generated from PC3, survivin protein levels controlled both cell viability and LC3 localization in response to CCL2 treatment. Altogether, these findings indicate that CCL2 protects prostate cancer PC3 cells from autophagic death via the phosphatidylinositol 3-kinase/Akt/survivin pathway and reveal survivin as a critical molecule in this survival mechanism.


Promises on the go: A field study on keeping one's word.
Promises are voluntary commitments to perform a future action and are often thought to be powerful levers for behavioral change. Here we studied the effectiveness of promises in two preregistered, incentivized field experiments with German students (N = 406) on the premises of a cafeteria. In Experiment 1, the majority of participants (63%) kept their promise to pay back at least half of a € 4-endowment, even though there was no foreseeable cost of breaking the promise, reputational or otherwise. Significantly fewer participants (22%) paid back money in a control group that faced a simple decision to return money or not. In Experiment 2, the majority of participants (54%) kept their promise to add a provided stamp to a postcard and mail it back (anonymously) within a week. We found similar return rates (52%) for a second group for which the word "promise" was omitted from the commitment. Our findings show that participants kept their word outside the laboratory while pursuing everyday activities even when there were no foreseeable negative consequences for breaking them, demonstrating that promises are effective levers for behavioral change.


National Hospital Ambulatory Medical Care Survey: 1997 emergency department summary.
This report describes ambulatory care visits to hospital emergency departments in the United States. Statistics are presented on selected patient and visit characteristics. The data presented in this report were collected from the 1997 National Hospital Ambulatory Medical Care Survey (NHAMCS). NHAMCS is part of the ambulatory care component of the National Health Care Survey that measures health care utilization across various types of providers. NHAMCS is a national probability survey of visits to hospital emergency and outpatient departments of non-Federal, short-stay, and general hospitals in the United States. Sample data were weighted to produce annual estimates. During 1997, an estimated 94.9 million visits were made to hospital emergency departments (ED's) in the United States, about 35.6 visits per 100 persons. Persons 75 years and over had the highest rate of ED visits. There were an estimated 35.1 million injury-related ED visits during 1997, or 13.2 visits per 100 persons. Seventy percent of injury-related ED visits were made by persons under 45 years of age. Injury visit rates were higher for males than females in each age group under 45 years. According to ICD-9-CM classification, about four-fifths of injury visits were unintentional. Almost 72 percent of the ED visits involved medication therapy, with pain relief drugs accounting for almost 30 percent of the medications mentioned. Acute upper respiratory infection was the leading illness-related diagnosis at ED visits.


Use of host lipids by the Lyme disease spirochete may lead to biomarkers.
Lyme disease is the most common tick-borne disease in North America and Europe, however, current biomarkers inconsistently detect the disease. In this issue of the JCI, Gwynne et al. revealed how the Lyme disease agent Borrelia burgdorferi relies on host lipids for growth. The authors used a murine model to show that B. burgdorferi infection led to the production of antibodies against phospholipids, possibly as a consequence of incorporation into the spirochete membrane. Antibodies were induced against phosphatidic acid, phosphatidylcholine, and phosphatidylserine. Notably, no antibodies against cardiolipin were found, distinguishing Lyme disease from syphilis and some other diseases. Sera samples from patients with Lyme disease suggested that these antibodies may help diagnose B. burgdorferi infection and that antibody titers may effectively indicate the response to treatment. These findings suggest that B. burgdorferi-induced anti-lipid antibodies, in conjunction with a careful clinical assessment, may aid in the diagnosis of Lyme disease.


Initiation of HAART in drug-naive HIV type 1 patients prevents viral breakthrough for a median period of 35.5 months in 60% of the patients.
The introduction of potent combinations of antiviral drugs is a major breakthrough in the treatment of HIV. We investigated the long-term virologic outcome and the development of resistance after initiating highly active antiretroviral therapy (HAART) in drug-naive patients in daily clinical practice. Twenty-five treatment-naive HIV-1 patients were started on HAART. Fifteen patients responded with a drop in viral load below the limit of detection during 35.5 (interquartile range: 7) months of therapy. In 6 of 10 patients with virologic failure, virus with resistance-related mutations against the received drugs emerged. Compared with responders (R), nonresponding (NR) patients were in a later disease stage at therapy start (p = 0.0089) with lower CD4 cell counts at baseline (p = 0.040), and a lower proportion of nonresponders showed protease inhibitor (PI) levels above C(min) (p = 0.049). More NR patients showed secondary PI mutations at baseline (p = 0.079), and the CCR2-64I coreceptor polymorphism was absent among NR patients, compared with 38.5% of R patients displaying CCR2-64I (p = 0.053), although the differences were not significant. In conclusion, starting HAART in antiretroviral drug-naive HIV-infected patients followed in daily clinical practice prevented viral breakthrough for up to 44 months in 60% of the patients. Virologic failure was associated with the development of resistance-related mutations, a later stage of disease at start of therapy and lower PI drug levels.


Virus-like particles and double stranded RNA from killer and non-killer strains of Saccharomyces cerevisiae.
Virus-like particles and DsRNA found in extracts of killer, non-killer and suppressive non-killer strains were co-precipitated from cell extracts using an antibody prepared against purified virus-like particles isolated from a non-killer strain having only the higher molecular weight L dsRNA. The relative amount of virus-like particles correlated roughly with the amount of dsRNA: those strains with high concentrations of dsRNA had the most particles. When a preparation of particles was subjected to sucrose gradient velocity centrifugation, particles containing the S and M dsRNA could be separated from those containing the L dsRNA. These experiments taken together suggest that the L, M and S dsRNAs are separately encapsulated by the same protein coat.


Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019.
Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is required. To define pediatric-specific dosing regimens for hydroxychloroquine and remdesivir for COVID-19 treatment. Pharmacokinetic modeling and simulation were used to extrapolate investigated adult dosages toward children (March 2020-April 2020). Physiologically based pharmacokinetic modeling was used to inform pediatric dosing for hydroxychloroquine. For remdesivir, pediatric dosages were derived using allometric-scaling with age-dependent exponents. Dosing simulations were conducted using simulated pediatric and adult participants based on the demographics of a white US population. Simulated drug exposures following a 5-day course of hydroxychloroquine (400 mg every 12 hours × 2 doses followed by 200 mg every 12 hours × 8 doses) and a single 200-mg intravenous dose of remdesivir were computed for simulated adult participants. A simulation-based dose-ranging study was conducted in simulated children exploring different absolute and weight-normalized dosing strategies. The primary outcome for hydroxychloroquine was average unbound plasma concentrations for 5 treatment days. Additionally, unbound interstitial lung concentrations were simulated. For remdesivir, the primary outcome was plasma exposure (area under the curve, 0 to infinity) following single-dose administration. For hydroxychloroquine, the physiologically based pharmacokinetic model analysis included 500 and 600 simulated white adult and pediatric participants, respectively, and supported weight-normalized dosing for children weighing less than 50 kg. Geometric mean-simulated average unbound plasma concentration values among children within different developmental age groups (32-35 ng/mL) were congruent to adults (32 ng/mL). Simulated unbound hydroxychloroquine concentrations in lung interstitial fluid mirrored those in unbound plasma and were notably lower than in vitro concentrations needed to mediate antiviral activity. For remdesivir, the analysis included 1000 and 6000 simulated adult and pediatric participants, respectively. The proposed pediatric dosing strategy supported weight-normalized dosing for participants weighing less than 60 kg. Geometric mean-simulated plasma area under the time curve 0 to infinity values among children within different developmental age-groups (4315-5027 ng × h/mL) were similar to adults (4398 ng × h/mL). This analysis provides pediatric-specific dosing suggestions for hydroxychloroquine and remdesivir and raises concerns regarding hydroxychloroquine use for COVID-19 treatment because concentrations were less than those needed to mediate an antiviral effect.


Disability prevalence and disability-related employment gaps in the UK 1998-2012: Different trends in different surveys?
The persistently low employment rate among disabled individuals has been an enduring concern of governments across developed countries and has been the subject of a succession of policy initiatives, including labour market activation programmes, equality laws and welfare reform. A key indicator of progress is the trend in the disability-related employment gap, the percentage point difference between the employment rate for disabled and non-disabled individuals. Confusingly for the UK, studies undertaken between 1998 and 2012 have simultaneously reported both a widening and a narrowing of the gap. The source of the discrepancy can be found in the choice of survey, the General Household Survey (GHS) or the Labour Force Survey (LFS), although both use a common conception of disability and collect self-reported information from a random sample of households. The literature has analysed these surveys separately from each other and ignored inter-survey differences in findings. The Health Survey for England (HSE), a third national household survey, replicates the GHS questions on disability but has had limited use in this context. This empirical study compares the trends in disability prevalence and the disability-related employment gap across the three surveys using a three-stage harmonisation process. The negative relationship between the prevalence of disability and the employment gap found in cross-section inter-survey comparisons prompts an initial focus on differences in the definition of disability as an explanation of the discrepancy. This is broadened to include differences in survey methods and sample composition. Differences in the trend in disability prevalence and the employment gap remain following harmonisation for definition, survey method and sample composition. It is the LFS, the main policy-influencing and policy-assessment survey, which generates outlying results. As such, we cannot be confident that the disability-related employment gap has narrowed in the UK since 1998.