Wheat leaf lipids during heat stress: I. High day and night temperatures result in major lipid alterations.
Understanding how wheat (Triticum aestivum L.) plants under high temperature (HT) regulate lipid composition is critical to developing climate-resilient varieties. We measured 165 glycerolipids and sterol derivatives under optimum and high day and night temperatures in wheat leaves using electrospray ionization-tandem mass spectrometry. Levels of polar lipid fatty acyl chain unsaturation were lower in both heat-tolerant genotype Ventnor and susceptible genotype Karl 92 under HT, compared with optimum temperature. The lower unsaturation was predominantly because of lower levels of 18:3 acyl chains and higher levels of 18:1 and 16:0 acyl chains. Levels of 18:3-containing triacylglycerols increased threefold/more under HT, consistent with their possible role in sequestering fatty acids during membrane lipid remodelling. Phospholipids containing odd-numbered or oxidized acyl chains accumulated in leaves under HT. Sterol glycosides (SG) and 16:0-acylated sterol glycosides (ASG) were higher under HT than optimum temperatures. Ventnor had lower amounts of phospholipids with oxidized acyl chains under HT and higher amounts of SG and 16:0-ASG than Karl 92. Taken together, the data demonstrate that wheat leaf lipid composition is altered by HT, in which some lipids are particularly responsive to HT, and that two wheat genotypes, chosen for their differing physiological responses to HT, differ in lipid profile under HT.


Malignant fibrous histiocytoma arising from the renal capsule: report of a case.
We report a case of malignant fibrous histiocytoma arising from the renal capsule. The tumor was found during screening ultrasonography. Surgical excision and adjuvant chemotherapy consisting of cyclophosphamide, vincristine, adriamycin and actinomycin D were performed. There has been no recurrence as of 2 years and 4 months after the operation. We reviewed the 5 other cases of malignant fibrous histiocytoma arising from the renal capsule.


Ascaris suum - A zoonosis in Bali, Indonesia.
Ascariasis is a common disease in humans and pigs. In previous reports, it has been known that ascariasis in humans is not only caused by Ascaris lumbricoides but also by Ascaris suum which is known to originate from pigs. This research aims to identify the species of Ascaris that infect traditional pig farmers in Bali, Indonesia. To achieve this, an observational study was conducted, in which 239 feces samples were collected from traditional pig farmers. The collected samples were then divided into two parts, with one part stored in a pot containing 10% formalin for microscopic testing, and the other part stored in 70% ethanol for molecular testing. In cases where Ascaris infection was observed during the microscopic examination, a further test was conducted using the polymerase chain reaction (PCR) method for molecular examination. The DNA derived from the PCR was then subjected to DNA sequencing. The result was compared to A. suum gene data previously published in the Gene Bank. The results of the microscopic examination showed that 22 farmers were infected with Ascaris. However, PCR testing and DNA sequencing indicated that three infections were caused by A. suum. Therefore, it can be concluded that A. suum is a zoonosis in Bali. Thus, efforts to control ascariasis must pay attention to the presence of pigs around it. Handling of ascariasis is not only carried out in humans but also in pigs and the environment.


[Cristóbal de Vega (1510-1573), physician to prince Don Carlos (1545-1568)].
This paper represents biographical aspects concerning the always-delicate health of Prince Don Carlos (1545-1568), first-born son of the King Felipe II of Spain (1527-1598). The main conditions and circumstances of his pathobiography were drawn from interesting data offered by one of his royal doctors, the former professor of the University of Alcalá, Cristóbal de Vega (1510-1573), throughout his significant medical career. In particular, the report on the quartan fevers suffered by Don Carlos in Doctor Vega's Commentaria in librum Aphorismorum (1568), provides considerable and previously unknown clinical data on the disease.


Effect of Biological Maturation on Performance of the Athletic Ability Assessment in Australian Rules Football Players.
To determine the effect of biological maturation on athletic movement competency as measured using the Athletic Ability Assessment-6. Fifty-two junior Australian Rules football players were split into 3 groups based on proximity to peak height velocity, while 46 senior players were split into 2 groups based on playing status. The subjects completed the Athletic Ability Assessment-6 (inclusive of the overhead squat, double lunge, single-leg Romanian dead lift, push-up, and chin-up). All subjects were filmed and retrospectively assessed by a single rater. A 1-way analysis of variance and effect-size statistics (Cohen d) with corresponding 90% confidence intervals were used to describe between-groups differences in the component movement scores. The statistical significance was set a priori at P < .05. There were significant between-groups differences for all component movements (P < .05). Post hoc testing revealed that older, more mature subjects possessed greater competency in all movements except the overhead squat. The effect sizes revealed predominantly moderate to very large differences in competency between the senior and junior groups (range of d [90% confidence interval]: 0.70 [0.06 to 1.30] to 3.01 [2.18 to 3.72]), with unclear to moderate differences found when comparing the 3 junior groups (0.08 [-0.50 to 0.65] to 0.97 [0.22-1.61]). The findings suggest that biological maturation may be associated with changes in athletic movement competency in youth Australian Rules football players. Therefore, it is recommended that strength and conditioning coaches monitor maturity status when working with 12- to 15-y-old players. This can allow for a comparison of an individual's athletic movement competency to maturity-based standards and help guide developmentally appropriate training programs.


High- and low-sensitivity subforms of alpha4beta2 and alpha3beta2 nAChRs.
Previous studies in other laboratories have shown that alpha4beta2 nicotinic acetylcholine receptor (nAChR) exhibits a biphasic concentration-response relationship for ACh with low and high EC50 components, and that the low EC50 component can be augmented by decreasing the alpha4:beta2 message ratio or incubating overnight in nicotine or at low temperature (Zwart and Vijverberg, 1998; Covernton and Connolly, 2000; Buisson and Bertrand, 2001; Nelson et al., 2003; Zhou et al., 2003). In the process of cloning ferret nAChR subunits, we found alpha4 and beta2 messages with long untranslated regions (UTRs), as well as those with no UTRs. Combinations of these messages revealed that the presence of UTRs influenced the ability to exclusively express high-sensitivity subforms of alpha4beta2 and alpha3beta2 nAChRs. Injection of oocytes with alpha4 and beta2 RNAs lacking UTRs (1:1 ratio) led to expression of a biphasic concentration-response relationship for ACh with EC50 values of 0.5 (high sensitivity) and 114 microM(low sensitivity). Decreasing the alpha4:beta2 message ratio to as much as 1:120 increased the high-sensitivity component slightly, but the ACh concentration response remained biphasic. In contrast, injection of messages with UTRs (1:1 ratio) led to expression of a monophasic concentration response to ACh and a high-sensitivity EC50 value of 2.3 microM, as shown in Fig. 1.


Fenvalerate induces oxidative hepatic lesions through an overload of intracellular calcium triggered by the ERK/IKK/NF-κB pathway.
Fenvalerate (FEN), a mainstream pyrethroid pesticide, was initially recommended as a low-toxicity agent for controlling agricultural and domestic pests. Despite the widespread use of FEN worldwide, little data are available on FEN-induced hepatic lesions and molecular mechanisms. In the present study, we first performed an occupational cross-sectional study on FEN factory workers and found that the levels of serum alanine aminotransferase (ALT) and total antioxidant capacity increased, whereas malondialdehyde decreased in laborers in the working areas where the levels of airborne FEN were much higher compared with the office area. The results were then confirmed by animal experiments that abnormal hepatic histology, increased ALT level, and compromised hepatic oxidative capability were observed in rats exposed to a high concentration of FEN. Furthermore, the bioinformatics analysis of gene microarray in rat liver tissue showed that FEN significantly changed the expressions of genes related to the regulation of intracellular calcium ion homeostasis and the calcium signal pathway. Finally, the functional experiments in Buffalo rat liver (BRL) cells demonstrated that FEN first activated ERK MAPK, followed by IKK and NF-κB, which triggered the transcription of genes responsible for accelerating an overload of intracellular calcium ions, prompted reactive oxygen species generation in the mitochondria, and finally, induced hepatic cellular apoptosis. The calcium signaling pathway and in particular, an overload of intracellular calcium play a critical role in this pathophysiological process via the ERK/IKK/NF-κB pathway. Our study furthers the understanding of the mechanism of FEN-induced hepatic injuries and may have implications in the prevention and control of liver diseases induced by environmental pesticides.-Qiu, L.-L., Wang, C., Yao, S., Li, N., Hu, Y., Yu, Y., Xia, R., Zhu, J., Ji, M., Zhang, Z., Wang S.-L. Fenvalerate induces oxidative hepatic lesions through an overload of intracellular calcium triggered by the ERK/IKK/NF-κB pathway.


Observations upon the aetiology and treatment of complete rectal prolapse.
The classical abnormalities found in patients with complete rectal prolapse--wide deep pelvic peritoneal pouch, unsupported redundant rectum with long mesorectum, weak pelvic floor and anal sphincters--are probably effects rather than causes. "Pelvic floor weakness" must explain few cases, since old age, multiparity, uterine prolapse, are found in a minority. The fact that operations which do no more than fix the rectum in the sacral hollow are most successful and often cure incontinence if present is the best evidence that lack of support of the rectum is a prime cause of prolapse--but it is equally likely that such operations work by preventing intussusception, now regarded as the likely mechanism (rather than sliding herniation) of complete rectal prolapse. It is suggested that rectal prolapse is usually due to straining at defaecation against a closed levator-ani--anal-sphincter mechanism, producing prolapse of the rectum rather than incontinence of faeces. Such straining may be obsessive on the part of patients with psychosocial problems and reduced awareness that the rectum is empty; or it may be due to attempted defaecation with a full rectum in patients with reduced rectal sensation, failure of the afferent arc of the ano-rectal reflex and consequent absence of levator-ani--anal-sphincter relaxation.


Beta 2 microglobulin-like polypeptide of the goldfish, Carassius auratus.
Antisera to human beta 2 microglobulin (beta 2M) detected a plasma membrane molecule on goldfish (Carassius auratus) cells in immunofluorescence. A goldfish molecule detected by radioimmunoassay (RIA) co-eluted with human beta 2M on gel filtration. By affinity chromatography on immobilized antibody to human beta 2M, a molecule was purified (from extracts of goldfish) that showed, on SDS-polyacrylamide gel electrophoresis, a mobility similar to that of human beta 2M (apparent Mr 12,800 +/- 500).


Expression of Pisum sativum PsAO3 gene, which encodes an aldehyde oxidase utilizing abscisic aldehyde, is induced under progressively but not rapidly imposed drought stress.
Aldehyde oxidase (AO; EC 18.104.22.168) catalyzes the final step of abscisic acid (ABA) biosynthesis, which is the oxidation of abscisic aldehyde (ABAld) to ABA. Gene expression analyses indicate that the stress-induced Pisum sativum PsAOγ isoform, which effectively uses ABAld as a substrate, is encoded by the PsAO3 gene. PsAO3 was heterologously expressed in Pichia pastoris and the recombinant PsAO3 protein revealed substrate preferences highly similar to the native PsAOγ protein present in the pea leaves and roots. Both proteins prefer indole-3-aldehyde and naphthaldehyde as substrates, although high activities against abscisic aldehyde and citral were also observed. The Km values of PsAO3 for naphthaldehyde and abscisic aldehyde (4.6 and 5.1 μM, respectively) were the lowest among the substrates tested. PsAO3 activity was almost completely inhibited by potassium cyanide, diphenyleneiodonium, and methanol. Rapidly imposed drought stress did not increase the level of PsAO3 mRNA or activity of any AO isoform, although an enhanced ABA accumulation and induction of PsNCED2 and -3 (9-cis-epoxycarotenoid dioxygenase; EC 188.8.131.52) expression, both in the pea roots and leaves, was observed. During a progressively induced drought, the level of PsAO3 transcript and PsAOγ activity increased significantly in the roots and leaves, whereas ABA accumulation occurred only in the leaves where it was accompanied by induction of the PsNCED3 expression. Therefore, we suppose that next to NCED, also AO (mainly PsAOγ) might be involved in regulation of the drought-induced ABA synthesis. However, while the "constitutive activity" of PsAOγ is sufficient for the fast generation of ABA under rapid drought stress, the enhanced PsAOγ activity is required for the progressive and long-term ABA accumulation in the leaves under progressive drought stress.


Radiosensitizer EXO-miR-197-3p Inhibits Nasopharyngeal Carcinoma Progression and Radioresistance by Regulating the AKT/mTOR Axis and HSPA5-mediated Autophagy.
The biological functions of exosomes and microRNAs (miRs) in nasopharyngeal carcinoma (NPC) remain largely unexplored. Here, miR-197-3p was screened and identified, and whose level was reduced in serum and exosomes of patients with NPC. MiR-197-3p might be a good diagnostic and prognostic indicator. Our data showed that miR-197-3p expression was closely related to radioresistance, apoptosis, proliferation, migration, and survival of NPC. Inhibition of miR-197-3p expression in vitro could promote the proliferation and migration of NPC cells, while promotion of miR-197-3p expression in vivo could significantly inhibit the growth and enhance the radiosensitivity of NPC cells. From the perspective of mechanism, miR-197-3p could inhibit AKT/mTOR phosphorylation activation, inhibit an activated pathway of AKT/mTOR, target Heat Shock 70-kDa Protein 5(HSPA5) related to endoplasmic reticulum homeostasis, inhibit HSPA5-mediated autophagy, and reverse the radioresistance of NPC. Interestingly, exosomal miR-197-3p (EXO-miR-197-3p) reduced the proliferation and migration potential of NPC cells in vitro, and tumor growth and radioresistance of NPC cells in vivo. EXO-miR-197-3p inhibited NPC progression and radioresistance by regulating AKT/mTOR phosphorylation activation and HSPA5-mediated autophagy. In conclusion, our results highlight the potential of EXO-miR-197-3p as an effective radiosensitizer and therapeutic agent for refractory NPC.


Treatment approaches for interstitial cystitis: multimodality therapy.
Interstitial cystitis is an increasingly common disease characterized by urgency, frequency, and pelvic pain. Its etiology is poorly understood but is likely to be multifactorial. A proposed pathophysiology describing a cascade of events, including epithelial dysfunction, mast cell activation, and neurogenic inflammation, is presented. Using this model, multimodality therapy regimens have been developed that treat all components of this cascade. Multimodality therapy appears more effective than single agents in the treatment of interstitial cystitis.


The quality of health services provided to remote dwelling aboriginal infants in the top end of northern Australia following health system changes: a qualitative analysis.
In Australia the health outcomes of remote dwelling Aboriginal infants are comparable to infants in developing countries. This research investigates service quality, from the clinicians' perspective and as observed and recorded by the researcher, in two large Aboriginal communities in the Top End of northern Australia following health system changes. Data were collected from semi-structured interviews with 25 clinicians providing or managing child health services in the two study sites. Thirty hours of participant observation was undertaken in the 'baby-rooms' at the two remote health centres between June and December 2012. The interview and observational data, as well as field notes were integrated and analysed thematically to explore clinicians' perspectives of service delivery to infants in the remote health centres. A range of factors affecting the quality of care, mostly identified before health system changes were instigated, persisted. These factors included ineffective service delivery, inadequate staffing and culturally unsafe practices. The six themes identified in the data: 'very adhoc', 'swallowed by acute', 'going under', 'a flux', 'a huge barrier' and 'them and us' illustrate how these factors continue, and when combined portray a 'very chaotic system'. Service providers perceived service provision and quality to be inadequate, despite health system changes. Further work is urgently needed to improve the quality, cultural responsiveness and effectiveness of services to this population.


Uncertainty estimation related to analysis of volatile aromatic hydrocarbons by static headspace gas chromatography.
A study of the analysis of benzene, toluene, ethylbenzene and xylenes by static headspace gas chromatography illustrated the estimation of uncertainty associated with the influence of several parameters, such as preparation of the standard solutions, calibration of the instrument, recovery and limit of detection. The objective of the investigation was to indicate the contribution of each stage in the developed procedure on the uncertainty measurement of the determination of volatile aromatic hydrocarbons in surface and underground water. The uncertainty sources were identified and illustrated in an effect diagram. The data illustrated the evaluation of uncertainty by the quantification of the uncertainty arising separately from each source. It has been demonstrated that data can be used to estimate the uncertainty resulting from the combined effect of all sources.


Intention to undergo HIV testing and associated factors among women in one high-HIV prevalence city.
The objective of this study is to understand the rate of intention to undergo HIV testing and associated factors among women in a city with high HIV prevalence. A cross-sectional study was conducted among 293 women HIV/AIDS patients who were newly examined with HIV infection and aged ≥18 years from September to December 2012. Multivariate logistic regression analyses were used to identify the factors associated with intention to undergo HIV testing. The rate of intention to undergo HIV testing was 12.3%. Nearly 90% of participants had no intention of getting HIV tested, and the main reasons were "Never thought I would be HIV-infected" (78.2%) and "I did not feel sick, and it was impossible to be HIV-infected" (19.8%). The awareness rate of HIV knowledge was 67.8%, and 34.1% had casual heterosexual partners. Those who had casual heterosexual partners or had better HIV knowledge were more likely to have intention of getting HIV tested. The rate of intention to undergo HIV testing among women is low. AIDS health education programmess and public information campaigns should be initiated to improve knowledge about HIV and the risk of HIV infection, to encourage women to take HIV testing more promptly. It is also vital to take measures to reduce stigma against AIDS patients.


Influenza vaccination with a live attenuated vaccine.
Influenza is a highly contagious, acute respiratory illness with a long history of outbreaks dating back several centuries. Although immunization is an effective means of protection against influenza, vaccination rates have been suboptimal, especially among certain high-risk groups, including children and health care personnel. This article reviews basic information about influenza and immunization, discusses the relevance of children as vectors of disease, and highlights current information on FluMist, an intranasally administered, live attenuated influenza vaccine, including studies of its use compared with trivalent inactivated vaccine and in children.


Left-lateralization of resting state functional connectivity between the presupplementary motor area and primary language areas.
An abundance of evidence points to the role of a presupplementary motor area (pre-SMA) in human language. This study explores the pre-SMA resting state connectivity network and the nature of its connections to known language areas. We tested the hypothesis that by seeding the pre-SMA, one would be able to establish language laterality to known cortical and subcortical language areas. We analyzed data from 30 right-handed healthy controls and performed the resting state functional MRI. A seed-based analysis using a manually drawn pre-SMA region of interest template was applied. Time-course signals in the pre-SMA region of interest were averaged and cross-correlated to every voxel in the brain. Results show that the pre-SMA has significant left-lateralized functional connectivity to the pars opercularis within Broca's area. Among cortical regions, pre-SMA functional connectivity is strongest to the pars opercularis In addition, pre-SMA connectivity was shown to exist to other cortical language-association regions, including Wernicke's Area, supramarginal gyri, angular gyri, and middle frontal gyri. Among subcortical areas, considerable left-lateralized functional connectivity occurs to the caudate and thalamus, whereas cerebellar subregions show right lateralization. The current study shows that the pre-SMA most strongly connects to the pars opercularis within Broca's area and that cortical connections to language areas are left lateralized among a sample of right-handed patients. We provide resting state functional MRI evidence that the functional connectivity of the pre-SMA is involved in semantic language processing and that this identification may be useful for establishing language laterality in preoperative neurosurgical planning.


Renal amyloidosis and other fibrillar glomerular diseases.
Fibrillar glomerular diseases are defined by the ultrastructural accumulation of glomerular extracellular microfibrils or microtubules. The deposits have compositions particular to specific diseases, and it is important to distinguish among these clinical pathologic entities and their differing clinical implications. Amyloidosis and immunotactoid glomerulopathy are two examples of fibrillar glomerular diseases. Amyloidosis is a systemic disease in which the fibrils stain with Congo red and contain various biochemically distinct proteins that identify diseases with differing prognostic and therapeutic implications. Immunotactoid glomerulopathy is a primary glomerular disease, and the deposits contain immunoglobulins that do not stain with Congo red. In contrast to amyloidosis, division of immunotactoid glomerulopathy based on the immunoglobulin content or ultrastructural appearance of the deposits has no clinical relevance.


Targeting male mosquito swarms to control malaria vector density.
Malaria control programs are being jeopardized by the spread of insecticide resistance in mosquito vector populations. It has been estimated that the spread of resistance could lead to an additional 120000 deaths per year, and interfere with the prospects for sustained control or the feasibility of achieving malaria elimination. Another complication for the development of resistance management strategies is that, in addition to insecticide resistance, mosquito behavior evolves in a manner that diminishes the impact of LLINs and IRS. Mosquitoes may circumvent LLIN and IRS control through preferential feeding and resting outside human houses and/or being active earlier in the evening before people go to sleep. Recent developments in our understanding of mosquito swarming suggest that new tools targeting mosquito swarms can be designed to cut down the high reproductive rate of malaria vectors. Targeting swarms of major malaria vectors may provide an effective control method to counteract behavioral resistance developed by mosquitoes. Here, we evaluated the impact of systematic spraying of swarms of Anopheles gambiae s.l. using a mixed carbamate and pyrethroid aerosol. The impact of this intervention on vector density, female insemination rates and the age structure of males was measured. We showed that the resulting mass killing of swarming males and some mate-seeking females resulted in a dramatic 80% decrease in population size compared to a control population. A significant decrease in female insemination rate and a significant shift in the age structure of the male population towards younger males incapable of mating were observed. This paradigm-shift study therefore demonstrates that targeting primarily males rather than females, can have a drastic impact on mosquito population.


Prostate Cancer: Improving the Flow of Research.
Prostate cancer is the most common nonskin cancer diagnosed in U.S. men and kills over 27 000 men annually. Thus, improving the outcomes for patients diagnosed with this disease is imperative. There has been a considerable amount of research done over the past several decades resulting in more cures than ever, but the death rate is still unacceptable. This oration addresses the progress that we have made over the past several decades and outlines the work yet to be done, as well as some processes to make that work happen. © RSNA, 2018.


[RNA-metabolism in aging (author's transl)].
After intraperitoneal application of 14C-orotic acid the tracer distribution and the labelling of total RNA in different organs of two groups of Wistar rats (5 and 22,5 months old) were represented. After 60 min 2/3 of tracer were found in liver and kidney. The uptake by liver of old animals is decreased significantly. The interactions between the tracer distribution in the organism, the time related uptake by the organs, the organ function (influenced by methimazol) and the specific activity of RNA were represented. From the results the conclusion is drawn that the comparison of the specific activities of total RNA alone--especially in comparison of young with old animals--is not sufficient for the examination of RNA synthesis.


Lumbar Spinal Stenosis: Review Update 2022.
Patients with lumbar spinal stenosis (LSS) may experience neuropathic symptoms, such as back pain, radiating pain, and neurogenic claudication. Although the long-term outcomes of both nonsurgical and surgical treatments are similar, surgery may provide shortterm benefits, including improved symptoms and lower risk of falling. Decompression is mainly used for surgical treatment, and depending on the decompression degree and associated instability, combination therapy may be given. Minimally invasive surgery has been demonstrated to produce excellent results in the treatment of LSS. Thus, an approach aimed at understanding the overall pathophysiology and treatment methods of LSS is expected to have a better therapeutic effect.


Mutations in the BC-loop of the BKV VP1 region do not influence viral load in renal transplant patients.
The reactivation and replication of the BK polyomavirus (BKV) leading to BKV-associated nephropathy (BKVAN) is one of the major complications in renal transplantation patients. BKV isolates were classified into four subtypes (I-IV) based on genotype variations within the VP1-coding region. The type-specific amino acid differences cluster within the BC-loop of the major capsid protein VP1. As demonstrated in vitro, mutations in this region also play a role in the infectivity, attachment and stability of viral particles. Therefore, we analyzed the prevalence of BC-loop mutations in isolates of kidney transplant patients and compared their viral load in the urine. The VP1 subtyping regions of BKV isolates obtained from urine samples of 45 renal transplant patients were sequenced. The phylogenetic analysis of these sequences revealed that subtype I (66.67%) is the most prevalent genotype. The remaining isolates belong to subtype IV (33.33%). A high frequency of changes to specific amino acids within the BC-loop was identified among the BKV isolates from renal transplant patients. Patients with BKVAN exhibited a higher viral replication than patients without nephropathy. Although titers of isolates of subtype I were higher than titers of subtype IV isolates, the difference did not reach statistical significance. In addition, amino acid changes in the BC-loop did not influence the viral load and the incidence of BKVAN. These in vivo results demonstrate that high replication rates which serve as a predictive marker for BKVAN are not caused by altered receptor binding or affinity via mutated BC-loops.


Systematic review with meta-analysis: de novo non-alcoholic fatty liver disease in liver-transplanted patients.
De novo non-alcoholic fatty liver disease (NAFLD) in liver-transplanted patients for cirrhosis not due to non-alcoholic steatohepatitis (NASH) is becoming a growing phenomenon. We performed a systematic review and evaluated the prevalence of this event and possible associated factors. A literature search in medical databases (PubMed, MEDLINE/OVIDSP, Science Direct and EMBASE) was performed in March 2017. Relevant publications were identified in most important databases. We estimated the pooled prevalence of NAFLD and NASH in patients with liver transplant. The data have been expressed as proportions/percentages, and 95% confidence intervals (CI) were calculated, using the inverse variance method. Odd ratios (OR) and 95% confidence intervals (95% CI) were estimated. Twelve studies were selected, enrolling 2166 subjects overall undergoing post-liver transplant biopsy. The pooled weighted prevalence of de novo NAFLD was 26% (95% CI 20%-31%). The pooled weighted prevalence of NASH was 2% (95% CI 0%-3%). The highest prevalences of de novo NAFLD were found for patients transplanted for alcoholic cirrhosis (37%) and cryptogenic cirrhosis (35%) and for patients taking tacrolimus (26%). Tacrolimus showed a risk of NAFLD similar to ciclosporin (OR = 1.02, 95% CI 0.3-3.51). Patients undergoing liver transplant are more prone to experience diabetes, hypertension or dyslipidaemia, and NAFLD may be an important element in this context. In this study, we show how the prevalence of NASH tends to remain significant and similar to the general population. Moreover, this study suggests a possible association with specific transplant indications. Further studies are required to confirm these findings.


Discrimination among the clinical isolates of Candida albicans by amplification of the repetitive sequences, alts.
A primer pair, PB and BSH, which amplified alts, a portion of Candida albicans-specific repetitive sequence, RPS, gave stable and reproducible fingerprint patterns of the strains by polymerase chain reaction (PCR). We applied this method to clinical isolates of C. albicans for strain discrimination. Using PCR fingerprint patterns, we could analyze the relatedness of C. albicans strains including those isolated from children with leukemia and their bedside parents. The results indicated that PCR analysis targeting an alt region gives rise to the same conclusion as the previous study obtained by SmaI RFLP analysis.


Immunological identification of seminalplasmin in tissue extracts of sex glands of bull.
Using immunoglobulin G (IgG) antibodies raised against highly purified, homogeneous seminalplasmin, an antimicrobial protein of bovine seminal plasma, it has been shown that bovine ampullae, gland vesicularis and corpus prostate, but not testes and epididymis, contain seminalplasmin. The content as estimated by radioimmunoassay employing 125I-seminalplasmin was: ampullae, 267 +/- 13; gland vesicularis, 275 +/- 14; and corpus prostate, 445 +/- 22 micrograms per g wet weight of the tissue. Seminalplasmin, as characterized by high-performance liquid chromatography and in vivo inhibition of RNA synthesis in E. coli, was isolated from gland vesicularis. The seminalplasmin content of bovine seminal plasma was shown to be 1%. A chymotryptic peptide of seminalplasmin comprising residues 1-13 from the amino terminus was found to compete with 125I-seminalplasmin for binding to anti-seminalplasmin IgG.


Henoch-Schönlein purpura: report of case.
A case of Henoch-Schönlein purpura in a man has been presented. The patient was a typical candidate for the disease, with a history of major allergies and antecedent events of an upper respiratory infection and ingestion of at least two drugs previously implicated as etiologic agents. However, no specific allergen was identified and tests to verify it as an example of a circulating immune complex disease were not successful. The patient had many of the commonly found symptoms of HSP and additionally had the rare complications of both genital involvement and intraoral lesions. The disease ran its course in approximately eight weeks; there is little reason to believe that the patient will have a recurrence.


Pharmacological modification of the edema produced by combined infusions of prostaglandin E1 and bradykinin in canine forelimbs.
In dogs anesthetized with pentobarbital, 60 min local i.a. infusions of prostaglandin E1 (4 micrograms/min) together with bradykinin (10 micrograms base/min) into forelimbs perfused at a constant pump controlled flow rate produced decreases in perfusion pressure and very marked increases in lymph flow, lymph total protein concentration, total protein transport and weight (266 g). Pretreatment with indomethacin did not significantly reduce the very marked increases in these parameters produced by the combined prostaglandin E1-bradykinin infusions. Treatment with diphenhydramine completely prevented the increases in lymph flow, lymph total protein concentration, total protein transport, weight and vasodilation produced by infusions of histamine, but not those produced by infusions of prostaglandin E1 or bradykinin. Pretreatment with methylprednisolone prevented the increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by infusions of prostaglandin E1, but not those produced by infusions of high doses of histamine or bradykinin. Treatment with either methylprednisolone or diphenhydramine significantly reduced the very marked increases in these parameters produced by combined infusions of prostaglandin E1 and bradykinin to levels produced by infusions of bradykinin alone. Vasopressin or isoproterenol treatment essentially prevented the very marked increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by combined infusions of prostaglandin E1 and bradykinin. These data suggest that the potentiation of the bradykinin edema formation produced by prostaglandin E1 results from an endogenous release of histamine and that treatment with vasopressin or isoproterenol essentially prevents the development of edema produced by combined infusions of these autacoids. Moreover, the potentiation is not dependent on the vasodilator action of prostaglandin E1 as it may be demonstrated under constant controlled flow conditions.


Sentinel-node biopsy or nodal observation in melanoma.
We evaluated the contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma. Patients with a primary cutaneous melanoma were randomly assigned to wide excision and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred, or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy. Among 1269 patients with an intermediate-thickness primary melanoma, the mean (+/-SE) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6% in the biopsy group and 73.1+/-2.1% in the observation group (hazard ratio for recurrence[corrected], 0.74; 95% confidence interval [CI], 0.59 to 0.93; P=0.009). Five-year melanoma-specific survival rates were similar in the two groups (87.1+/-1.3% and 86.6+/-1.6%, respectively). In the biopsy group, the presence of metastases in the sentinel node was the most important prognostic factor; the 5-year survival rate was 72.3+/-4.6% among patients with tumor-positive sentinel nodes and 90.2+/-1.3% among those with tumor-negative sentinel nodes (hazard ratio for death, 2.48; 95% CI, 1.54 to 3.98; P<0.001). The incidence of sentinel-node micrometastases was 16.0% (122 of 764 patients), and the rate of nodal relapse in the observation group was 15.6% (78 of 500 patients). The corresponding mean number of tumor-involved nodes was 1.4 in the biopsy group and 3.3 in the observation group (P<0.001), indicating disease progression during observation. Among patients with nodal metastases, the 5-year survival rate was higher among those who underwent immediate lymphadenectomy than among those in whom lymphadenectomy was delayed (72.3+/-4.6% vs. 52.4+/-5.9%; hazard ratio for death, 0.51; 95% CI, 0.32 to 0.81; P=0.004). The staging of intermediate-thickness (1.2 to 3.5 mm) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy. (ClinicalTrials.gov number, NCT00275496 [ClinicalTrials.gov].).


The Structural Determinants of Intra-Protein Compensatory Substitutions.
Compensatory substitutions happen when one mutation is advantageously selected because it restores the loss of fitness induced by a previous deleterious mutation. How frequent such mutations occur in evolution and what is the structural and functional context permitting their emergence remain open questions. We built an atlas of intra-protein compensatory substitutions using a phylogenetic approach and a dataset of 1,630 bacterial protein families for which high-quality sequence alignments and experimentally derived protein structures were available. We identified more than 51,000 positions coevolving by the mean of predicted compensatory mutations. Using the evolutionary and structural properties of the analyzed positions, we demonstrate that compensatory mutations are scarce (typically only a few in the protein history) but widespread (the majority of proteins experienced at least one). Typical coevolving residues are evolving slowly, are located in the protein core outside secondary structure motifs, and are more often in contact than expected by chance, even after accounting for their evolutionary rate and solvent exposure. An exception to this general scheme is residues coevolving for charge compensation, which are evolving faster than noncoevolving sites, in contradiction with predictions from simple coevolutionary models, but similar to stem pairs in RNA. While sites with a significant pattern of coevolution by compensatory mutations are rare, the comparative analysis of hundreds of structures ultimately permits a better understanding of the link between the three-dimensional structure of a protein and its fitness landscape.


Legal medicine implications of a multidisciplinary approach to managing Traumatic Encephalopathy Syndrome in Australia.
The medical profession has a fundamental obligation to accurately diagnose and effectively treat a range of diseases and conditions. In the case of Traumatic Encephalopathy Syndrome (TES), where there are no universally accepted clinical diagnostic criteria, a clear clinical diagnosis can pose significant challenges for healthcare providers and for subsequent appropriate management. "Nihilism" or an uncertain working diagnosis is not acceptable in the medical field and deserves further consideration. This paper explores the legal obligations that are placed upon healthcare professionals, both individually and as a part of a multidisciplinary team. This article analyses the responsibilities and expectations of medical professionals in diagnosing and treating complex medical conditions, such as TES. The authors address legal issues that must be considered for an effective operation of integrated medicine to enhance the overall quality of care and improving patient outcomes for those affected with underlying Chronic Traumatic Encephalopathy (CTE).


Dominant lethal mutations in the plasma membrane H(+)-ATPase gene of Saccharomyces cerevisiae.
The plasma membrane H(+)-ATPase of Saccharomyces cerevisiae is an essential protein that is required to establish cellular membrane potential and maintain a normal internal pH. An Asp-378 to Asn substitution at the residue phosphorylated during catalysis is dominant lethal when the pma1-D378N mutation is expressed along with a wild-type plasma membrane H(+)-ATPase (PMA1) gene. Several mutations in the first two putative transmembrane domains are also dominant lethal. However, these dominant lethal mutants often appear to be innocuous, because they are frequently lost by gene conversion to the wild-type sequence during the process of introducing the mutant sequence and subsequently removing the wild-type gene. Loss of the mutation by gene conversion does not occur while introducing recessive lethal mutations. Cells carrying the wild-type PMA1 gene on the chromosome and a dominant lethal mutation under the control of a GAL1 promoter on a centromere-containing plasmid exhibit a galactose-dependent lethality. Indirect immunofluorescence staining using anti-Pma1 antibodies shows that induction of dominant lethal PMA1 mutations leads to the accumulation of a number of intensely staining cytoplasmic structures that are not coincident with the nucleus and its immediately surrounding endoplasmic reticulum. These structures also accumulate the endoplasmic reticulum protein Kar2. Expression of the dominant lethal protein also prevents transport of the wild-type ATPase to the plasma membrane.


Lung Re-transplantation after prolonged veno-venous extracorporeal membrane oxygenation (ECMO) in a child with chronic lung allograft dysfunction.
Extracorporeal Membrane Oxygenation (ECMO) may be used as a bridge to lung transplantation in selected patients with end-stage respiratory failure. Historically, ECMO use in this setting has been associated with poor outcomes Puri V et.al, J Thorac Cardiovasc Surg, 140:427. More recently, technical advances and the implementation of rehabilitation and ambulation while awaiting transplantation on ECMO have led to improved surgical and post-transplant outcomes Kirkby S et.al, J Thorac Dis, 6:1024. We illustrate the case of a 6-year-old child who received prolonged ECMO support as a bridge to lung re-transplantation secondary to Chronic Lung Allograft Dysfunction (CLAD). Early rehabilitation was key in improving the overall pre-transplant conditioning during ECMO. Despite challenges associated with awake/ambulatory ECMO, the use of this strategy as a bridge to lung transplantation is feasible and has resulted in improved pre-transplant conditioning and post-transplant outcomes.


Biomechanical analyses of the human flexor tendon adhesion models in the hand: A cadaveric study.
Patients with longstanding trigger finger may develop flexion contracture at the proximal interphalangeal (PIP) joint that persists even after division of the A1 pulley. The purpose of this study was to explore the hypothesis that flexion deformity of the PIP joint in advanced trigger finger is caused by severe adhesion between the flexor digitorum superficialis (FDS) and the flexor digitorum profundus (FDP) tendons. Ten freshly frozen cadaveric hands were used in the experiments. After preparation of the extrinsic flexor, extrinsic extensor, and intrinsic muscle tendons, we applied weights to the flexor tendons and minimal tension to the extrinsic extensor and intrinsic muscle tendons. We then measured the initial flexion angles of the metacarpophalangeal (MCP) and PIP joints. Next, we measured the flexion angles of the MCP and PIP joints as increasing tension was applied to the extrinsic extensor and intrinsic muscle tendons, respectively. We repeated these experiments after constructing flexor tendon adhesion model. The initial flexion angles of the MCP and PIP joints were greater in the adhesion model, as were the average tensions required for full extension of these joints. Our results suggest that adhesion between two flexor tendons contributes to progression of flexion deformity in the PIP joint.


Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters.
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD. These factors may result in altered expression and activity of drug metabolizing enzymes (DMEs) or transporters. Existing evidence suggests that the effect of NAFLD on CYP3A4, CYP2E1 and MRP3 is more consistent across rodent and human studies. CYP3A4 activity is down-regulated in NASH whereas the activity of CYP2E1 and the efflux transporter MRP3 is up-regulated. However, it is not clear how the majority of CYPs, UGTs, SULTs and transporters are influenced by NAFLD either in vivo or in vitro. The alterations associated with NAFLD could be a potential source of drug variability in patients and could have serious implications for the safety and efficacy of xenobiotics. In this review, we summarize the effects of NAFLD on the regulation, expression and activity of major DMEs and transporters. We also discuss the potential mechanisms underlying these alterations.


Pharmacokinetic drug evaluation of safinamide mesylate for the treatment of mid-to-late stage Parkinson's disease.
Patients with Parkinson's disease suffer from a heterogeneous expression of neurotransmitter deficits. They cause an individual variable expression of motor and non-motor symptoms. Thus, drugs with various mechanisms of actions are suitable to counteract these disease related neurotransmitter alterations. Areas covered: This invited review suggests safinamide as an ideal compound for therapy of Parkinson's disease, as its pharmacological profile includes reversible monoamine oxidase B inhibition, blockage of voltage-dependent sodium channels, modulation of calcium channels and abnormal glutamate release. Safinamide may provide benefits effects on non-motor symptoms in addition to the demonstrated amelioration of motor impairment in levodopa treated patients with Parkinson's disease. Safinamide was well tolerated and safe when administered in dose of 50 or 100 mg daily in pivotal trials. Expert opinion: Clinical handling, safety and tolerability of Safinamide are better than of dopamine agonists or levodopa. Safinamide supplements the existing armamentarium of drugs for Parkinson's disease. Safinamide will help to reduce dosing of levodopa but also of dopamine agonists during long term treatment in patients with Parkinson's disease.


Impact of Vancomycin MIC on Clinical Outcomes of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia Treated with Vancomycin at an Institution with Suppressed MIC Reporting.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of bacteremia and is associated with significant morbidity and mortality. Prior studies evaluating the association of vancomycin MICs with clinical outcomes in patients with MRSA bacteremia have been inconsistent. This study evaluated the association between vancomycin MICs and 30-day in-hospital mortality rates for patients with MRSA bacteremia. This was a retrospective cohort study of patients with MRSA bacteremia treated with vancomycin for ≥72 h from January 2013 to August 2016. Vancomycin MICs were determined by broth microdilution via automated susceptibility testing methods. Study groups consisted of patients with MRSA isolates that had vancomycin MICs of <2 μg/ml and those with vancomycin MICs of 2 μg/ml. Covariates included demographics, severity of illness, comorbidities, intensive-care unit (ICU) admission, infectious disease consultation, infectious sources, and hospital onset of bacteremia. The primary outcome was 30-day in-hospital mortality. Secondary outcomes included the duration of bacteremia, persistent bacteremia for ≥7 days, recurrence within 30 days, change to alternative antibiotic therapy, and length of hospital stay. Multivariate logistic regression models were analyzed to control for potential confounding variables. A total of 166 patients were included for analysis: 91 patients with vancomycin MICs of <2 μg/ml and 75 patients with vancomycin MICs of 2 μg/ml. In the multivariate logistic regression model, a vancomycin MIC of 2 μg/ml, compared to a MIC of <2 μg/ml, was not significantly associated with 30-day in-hospital mortality after adjustment for confounders. Additionally, all secondary outcomes were not statistically significantly different between study groups. In patients with MRSA bacteremia treated with vancomycin, the vancomycin MIC was not associated with differences in clinical outcomes.


Relationship of epidermal growth factor binding capacity to histopathologic features and prognosis in human renal cell carcinoma.
We studied the association between epidermal growth factor (EGF) binding capacity and histopathologic features or prognosis in human renal cell carcinoma (RCC) by Scatchard analysis in 67 patients. EGF binding capacity was significantly greater in metastatic than in nonmetastatic tumors, and in nuclear grade 3 than nuclear grade 1 tumors. Multivariate analysis revealed that tumor stage, nuclear grade, EGF binding capacity, and tumor size significantly correlated with overall survival. These results suggest that EGF binding may be an important determinant of prognosis in patients with RCC.


Polymorphisms in Toll-like receptor genes are associated with vitiligo.
The members of Toll-like receptor (TLR) family are responsible for recognizing various molecular patterns associated with pathogens. Their expression is not confined to immune cells and have been detected in skin cells such as keratinocytes and melanocytes. As part of a generated response to pathogens, TLRs are involved in inducing inflammatory mediators to combat these threats. It is therefore not surprising that TLRs have been implicated in inflammatory skin diseases, including atopic dermatitis and psoriasis. Likewise, as key players in autoimmunity, they have been associated with a number of autoimmune diseases. Based on this, the role of TLRs in vitiligo could be suspected, but is yet to be clearly established. In order to conduct a genetic association analysis, 30 SNPs were selected from TLR1-TLR8 and TLR10 regions to be genotyped in Estonian case-control cohort consisting of 139 vitiligo patients and 307 healthy control individuals. The patients were further analyzed in subgroups based on sex, age of onset, occurrence of vitiligo among relatives, extent of depigmented areas, vitiligo progression activity, appearance of Köbner's phenomenon, existence of halo naevi, and incidence of spontaneous repigmentation. The most notable finding came with SNP rs179020 situated in TLR7 gene, that was associated in entire vitiligo (Padj = 0.0065) and also several subgroup analyses. Other single marker and haplotype analyses pointed to TLR3, TLR4, and TLR10 genes. This study investigated the genetic regions of nine TLR genes in relation to vitiligo susceptibility. The main results were the associations of TLR7 SNPs with vitiligo, while several other associations were obtained from the remaining TLR gene regions. This suggests that in addition to other inflammatory skin diseases, TLRs affect the development of vitiligo, thus making them interesting targets for future research.


Brain activation of eye movements in subjects with refractive error.
Recent functional magnetic resonance imaging (fMRI) studies have described reorganized activation of the oculomotor and visual cortex after focal brain lesions. These studies are based on comparison with healthy individuals who may have a very heterogenous refractive error. The influence of refractive error on the cortical control of an oculomotor task such as a prosaccade trial, however, is unknown. To investigate the influence of visual acuity on changes of cortical oculomotor control, we studied the representation of visually guided prosaccades in nine subjects with refractive error and 11 normally sighted subjects using fMRI. Correction of refractive error was not allowed during fMRI. Differences in activation between rest and saccades as well as between subjects with refractive error vs subjects with normal vision were assessed with statistical parametric mapping. In both groups, activation of a frontoparietal network was observed. Subjects with refractive errors showed increased activation compared to normally sighted subjects, with overactivation in bilateral frontal and parietal eye fields, supplementary eye fields, as well as in the bilateral extrastriate cortex. This group of subjects with refractive error showed increased activation in an extended oculomotor and visual network to maintain performance during simple prosaccades. This observation underlines the importance of using appropriate control groups in fMRI-studies after brain lesions.


Association of a Sindbis-like virus with Ockelbo disease in Sweden.
An alphavirus isolated from Culiseta mosquitoes has been associated with Ockelbo disease, an exanthema arthralgia syndrome occurring in Sweden. The isolate was made from mosquitoes collected in Edsbyn (central Sweden), an area with considerable Ockelbo disease morbidity. This isolate proved to be indistinguishable from Sindbis virus by complement-fixation and hemagglutination-inhibition tests, and was antigenically related to Sindbis in plaque reduction neutralization tests. Patients with Ockelbo disease developed neutralizing antibodies to the virus in their convalescent sera, suggesting that it is the etiologic agent of the disease.


The burden of tooth loss in Italian elderly population living in nursing homes.
This survey aims to evaluate the prevalence and severity of tooth loss in the Italian elderly population living in nursing homes and to associate the oral data with demographic, socioeconomic factors, the Mini-Mental State Examination (MMSE), the Body Mass Index (BMI) and the Mini Nutritional Assessment (MNA) scores. A cluster sample method was performed using each nursing home as a cluster. Twenty-three nursing homes located in the five areas of the Italy (North-West, North-East, Centre, South and Islands) were selected. An informed consent to participate was distributed by the personnel of the selected nursing homes and signed directly by subjects/caregivers; 2114 forms were distributed, 1998 forms signed and finally 1976 subjects were examined. Chewing ability was scored as good (≥10 functional units (FUs)), sufficient (7-10 FUs), and insufficient (< 7 FUs). The presence of prosthetic dental restorations was summarized as: absent of prosthesis, fixed prosthesis, removable prosthesis, combined prosthesis. Age, gender, socioeconomic status, MMSE, BMI and MNA were obtained from medical charts. Almost three quarters of the subjects were ≥ 80 years old (74.37%) and women (74.04%). The prevalence of edentulism was 42.10% with a large variation among the five areas of Italy (from 34.43% in Centre to 53.46% in North-West). Insufficient presence of FUs was preeminent in each age group (prevalence 42.10%) and statistically associated to age and to female gender (p < 0.01). Overweight/obese (7.47%) subjects showed the highest FUs. Area of living, MMSE (both < 0.01), BMI (p = 0.01) were statistically significant associated to the type of prosthetic dental restorations in the oldest group. Subjects with no mental impairment showed the highest percentage of prosthetic dental restorations (32.36%). More than half of the sample has an insufficient number of functional units for chewing and this is more pronounced in females. The presence and the type of prosthetic dental restorations are linked to cognitive impairment: the higher is the mental impairment the higher is the number of subjects with absence of prosthetic restorations. The findings of this national survey highlight the need for public health policy, aiming to increase awareness regarding oral health though health education.


Computed tomography-based surgical navigation for hip arthroplasty.
Component malpositioning and postoperative leg length discrepancy are the most common technical problems associated with total hip arthroplasty (THA). Surgical navigation offers the potential to reduce the incidence of these problems. We reviewed 317 patients (344 hips) that underwent THA using computed tomography-based surgical navigation, including 112 THAs using a simplified method of measuring leg length. Guided by the navigation system, cups were placed in 40.8 degrees +/- 2 degrees of operative abduction (range, 35 degrees -50 degrees) and 30.8 degrees +/- 3.2 degrees (range, 19 degrees -43 degrees) of operative anteversion. We subsequently measured radiographic abduction on plain anteroposterior pelvic radiographs and calculated abduction and anteversion. Radiographically, 97.1 % of the cups were in the safe zone for abduction and 92.4% for anteversion. The mean incision length was less than 8 cm for 327 of the 344 hips. Leg length change measured intraoperatively was 6.6 +/- 4.1 mm (range, -2-22), similar to measurements from the pre- and postoperative magnification-corrected radiographs. Computer assistance during THA increased the consistency of component positioning and allowed reliable measurement of leg length change during surgery.


Occupational health practice in New Zealand.
On the basis of the national un-funded liability for work injuries and illnesses, and comparisons of health outcome and cost data to a benchmark, it can be concluded that occupational health practice in New Zealand is deficient. This deficiency persists despite recent legislative reforms and is due to a combination of Accident Rehabilitation and Compensation Insurance Corporation, health professional and industrial factors. It is clear that a comprehensive corrective strategy is needed to attend to: the up-skilling of health case managers and the medical profession in concert; and, to encouraging employers to introduce comprehensive occupational health programmes.


Basis and use of a true monopolar derivation: the neo-electroencephalography (N.E.E.G.).
A new method of monopolar recording is presented. This true monopolar derivation is based on a computer-reconstituted signals method: use of a reference electrode obtained by interconnecting two electrodes placed one on either side of the neck to form a common pole; detection by Fourier analysis of the various frequencies from 0 to 16 Hz in 1/4 Hz steps; continuous comparison of phase for each activity per 1/4 Hz between the signal PF left - Reference Neck (RC) and O right - Reference Neck (RC) in order to see whether the reference electrode is active or not; automatic subtraction of the value of the reference electrode from the value of all other reference channels if the reference electrode is active. The technique is available for routine purposes. The results are easy to read and provide more precise data as well as new parameters which could prove useful in current clinical practice. The first electroclinical correlations covered frequency, location of potential gradients and phase relations established for 40 adult normal subjects with a reading identified as normal, and for 60 adult pathological subjects with a reading also identified as normal. Clear differences appeared between these two types of supposedly normal readings.


[Episodic and prospective memory impairment: impact, assessment and cognitive rehabilitation].
Deficits of episodic memory and subjective memory complaints are common in adults with acquired brain injury. These impairments are likely to have a negative impact on daily activities and vocational integration. Neuropsychological assessments examine their degree of severity, the nature of the impaired processes and the presence of other, associated cognitive or affective symptoms. Cognitive rehabilitation mainly aims at reducing the impact of persisting memory difficulties on everyday life using compensation strategies. Cognitive rehabilitation studies have improved their quality in the last decade, as indicated by the increased number of randomized controlled trials and demonstrated the efficacy of some therapeutic interventions on various variables.


Caging-Pnictogen-Induced Superconductivity in Skutterudites IrX3 (X = As, P).
Here, we report on a new kind of compound, XδIr4X12-δ (X = P, As), the first hole-doped skutterudites superconductor. We provide atomic-resolution images of the caging As atoms using scanning transmission electron microscopy (STEM). By inserting As atoms into the caged structure under a high pressure, superconductivity emerges with a maximum transition temperature (Tc) of 4.4 K (4.8 K) in IrAs3 (IrP3). In contrast to all of the electron-doped skutterudites, the electronic states around the Fermi level in XδIr4X12-δ are dominated by the caged X atom, which can be described by a simple body-centered tight-binding model, implying a distinct pairing mechanism. Our density functional theory (DFT) calculations reveal an intimate relationship between the pressure-dependent local-phonon mode and the enhancement of Tc. The discovery of XδIr4X12-δ provides an arena to investigate the uncharted territory of hole-doped skutterudites, and the method proposed here represents a new strategy of carrier doping in caged structures, without introducing extra elements.


[Laveran, Marchiafava and paludism].
The discovery in 1880 of the malaria parasite by the French investigator Alphonse Laveran found for almost ten years the obstinate refusal from the italian Ettore Marchiafava, who saw in the parasitic elements only degenerative forms of the erythrocytes. The acknowledgement for Laveran came in 1889 with the Bréant Prize and later the Nobel of 1907, half of which he gave to the Pasteur Institute. By his side, Marchiafava demonstrated the transmission of malaria man to man by the blood of the sick, through experiences to day inadmissible for any ethical committee. From the classic textbook of Laveran Du paludisme et de son hématozoaire, published in 1891, the history of this discovery is revised in the author's words.


The anticonvulsant enaminone E139 attenuates paclitaxel-induced neuropathic pain in rodents.
The enaminone methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139) has anticonvulsant activities. It has been reported to have a better safety profile than some anticonvulsant drugs. Since some anticonvulsant drugs are used in the management of neuropathic pain, we evaluated the effects of E139 in rodent models of acute pain and paclitaxel-induced neuropathic pain. The reaction latency to thermal stimuli (hot-plate test) of BALB/c mice was recorded before and after intraperitoneal treatment with paclitaxel (2 mg/kg, i.p. for 5 consecutive days), and after treatment with E139 (0.1-40 mg/kg), amitriptyline (10 mg/kg), and gabapentin (10 and 30 mg/kg). Mechanical allodynia in paclitaxel-treated Sprague Dawley (SD) rats was measured using a dynamic plantar aesthesiometer before and after treatment with E139 (10 and 20 mg/kg) or its vehicle for four consecutive days from day 7 after first administration of paclitaxel (16 mg/kg on two alternate days). Administration of E139 (10-40 mg/kg) produced antinociceptive activity against thermal nociception in naïve mice. Treatment with E139, amitriptyline, or gabapentin reduced paclitaxel-induced thermal hyperalgesia. E139 reduced paclitaxel-induced mechanical allodynia, with the effects lasting longer (24 h) after repetitive dosing. Our results indicate that E139 has antinociceptive activity and attenuates paclitaxel-induced neuropathic pain in rodents.


Enhanced clinical-scale manufacturing of TCR transduced T-cells using closed culture system modules.
Genetic engineering of T-cells to express specific T cell receptors (TCR) has emerged as a novel strategy to treat various malignancies. More widespread utilization of these types of therapies has been somewhat constrained by the lack of closed culture processes capable of expanding sufficient numbers of T-cells for clinical application. Here, we evaluate a process for robust clinical grade manufacturing of TCR gene engineered T-cells. TCRs that target human papillomavirus E6 and E7 were independently tested. A 21 day process was divided into a transduction phase (7 days) and a rapid expansion phase (14 days). This process was evaluated using two healthy donor samples and four samples obtained from patients with epithelial cancers. The process resulted in ~ 2000-fold increase in viable nucleated cells and high transduction efficiencies (64-92%). At the end of culture, functional assays demonstrated that these cells were potent and specific in their ability to kill tumor cells bearing target and secrete large quantities of interferon and tumor necrosis factor. Both phases of culture were contained within closed or semi-closed modules, which include automated density gradient separation and cell culture bags for the first phase and closed GREX culture devices and wash/concentrate systems for the second phase. Large-scale manufacturing using modular systems and semi-automated devices resulted in highly functional clinical-grade TCR transduced T-cells. This process is now in use in actively accruing clinical trials and the NIH Clinical Center and can be utilized at other cell therapy manufacturing sites that wish to scale-up and optimize their processing using closed systems.


Pip, a novel activator of phenazine biosynthesis in Pseudomonas chlororaphis PCL1391.
Secondary metabolites are important factors for interactions between bacteria and other organisms. Pseudomonas chlororaphis PCL1391 produces the antifungal secondary metabolite phenazine-1-carboxamide (PCN) that inhibits growth of Fusarium oxysporum f. sp. radius lycopersici the causative agent of tomato foot and root rot. Our previous work unraveled a cascade of genes regulating the PCN biosynthesis operon, phzABCDEFGH. Via a genetic screen, we identify in this study a novel TetR/AcrR regulator, named Pip (phenazine inducing protein), which is essential for PCN biosynthesis. A combination of a phenotypical characterization of a pip mutant, in trans complementation assays of various mutant strains, and electrophoretic mobility shift assays identified Pip as the fifth DNA-binding protein so far involved in regulation of PCN biosynthesis. In this regulatory pathway, Pip is positioned downstream of PsrA (Pseudomonas sigma factor regulator) and the stationary-phase sigma factor RpoS, while it is upstream of the quorum-sensing system PhzI/PhzR. These findings provide further evidence that the path leading to the expression of secondary metabolism gene clusters in Pseudomonas species is highly complex.


Effects of astigmatism and coma on rotating point spread function.
Rotating point spread function (PSF) provides a novel approach to detect three-dimensional position. As the optical aberration of a system can hardly be removed completely, effects of aberration on the PSF were studied both analytically and numerically. Results show that the intensity pattern is robust to both astigmatism and coma, while astigmatism affects the rotating angle of the PSF, and coma affects the lateral position of the PSF.


Self-Perception of Physical Function Contributes to Participation in Cognitively- and Physically-Demanding Activities After Stroke.
Background: Persons with and without aphasia experience decreased participation in meaningful activities post-stroke that result in reduced autonomy and poorer quality of life. Physical, cognitive, and/or communication deficits are prevalent post-stroke and many activities given up are purported to require high levels of communicative, cognitive, or physical skill. However, the relationship between deficits after stroke and participation in life activities that appear to require high skill levels in these three areas has not been investigated fully. Objectives: The objectives of this study are to: (1) determine differences in reported participation in communicatively-, cognitively-, or physically-demanding activities in persons after stroke with and without aphasia living in the community, and to (2) investigate whether performance on commonly used self-perception assessments of these three areas predicts reported participation in activities requiring higher levels of skill in these domains. Methods: In a cross-sectional design, 82 individuals at least 6 months post-stroke with (N = 34) and without aphasia (N = 48) were administered a battery of neuropsychological and participation-based assessments. Supported communication techniques maximized inclusion of individuals with aphasia. A series of regression analyses investigated the relationship between self-perceived communicative, cognitive, and physical functioning and reported participation in activities post-stroke that required high amounts of skilled function in these areas. Results: People with and without aphasia did not differ in terms of the percentage retained in communicatively-, cognitively-, or physically-demanding activities. All individuals retained higher levels of participation in communicatively- and cognitively-demanding activities (at least 60% retained), compared to participation inphysically-demanding activities (about 50% retained). The strongest predictor for retaining participation in two of the three domains of activities was self-perception of physical function, though much of the variance remained unexplained. Self-perception of communication was not related to participation retention in any of the three domains. Significance of Impact: Rehabilitation professionals should be aware of the impact that a variety of communicative, cognitive, and physical factors may have on participation post-stroke. Self-perceptions of impairments in communication and cognition may not directly predict participation in activities requiring high levels of communicative and/or cognitive skill, at least for those with mild impairment, even though activities requiring those skills are given up or done less after stroke.


Hemogram responses in goats toward challenged with Corynebacterium pseudotuberculosis and its immunogen mycolic acids.
This study was conducted to analyze the changes in blood profile of goats inoculated with Corynebacterium pseudotuberculosis and its immunogen mycolic acid (MA) extract. A total of 12 clinically healthy crossbred Boer female goats were divided into three groups; A, B and C (4 goats each per group). Group A was inoculated with 2 ml sterile phosphate buffered saline via intradermal route as the negative control group whilst Group B was inoculated with 2 ml of MA extract (1 g/ml) intradermally and Group C was then inoculated with 2 ml (1×109) colony forming unit of active C. pseudotuberculosis intradermally. Blood sample was collected aseptically from the jugular vein periodically for complete blood count (CBC) analysis throughout the experimental period (3 months). A significant decrease (p<0.05) was observed in red blood cells, hemoglobin (Hb), packed cell volume, mean corpuscular volume and mean corpuscular Hb concentration in Groups B and C as compared to the control while WBCs, neutrophil, lymphocyte and basophil showed a significant increase (p<0.05) as compared to the control. The inoculation of C. pseudotuberculosis and MA resulted in a significant change in the CBC, thereby, indicating that MA has a role in caseous lymphadenitis pathogenesis.


Human pathogens associated with raw produce and unpasteurized juices, and difficulties in decontamination.
The ability of public health agencies to identify, through enhanced epidemiologic and surveillance techniques, raw fruits, vegetables, and unpasteurized juices as probable sources of infectious microorganisms, has undoubtedly resulted in increased numbers of documented outbreaks. Changes in agronomic, harvesting, distribution, processing, and consumption patterns and practices have also likely contributed to this increase. The risk of illness associated with raw produce and unpasteurized produce products can be reduced by controlling or preventing contamination, or by removing or killing pathogenic microorganisms by washing or treating them with sanitizers. However, the hydrophobic cutin, diverse surface morphologies, and abrasions in the epidermis of fruits and vegetables limit the efficacy of these treatments.


[The 5S rRNA-protein complex of Escherichia coli studied by carbodiimide modification].
5S rRNA-protein complex has been reconstituted from 5S rRNA and total protein of large (L) ribosomal subunit of Escherichia coli. The complex consists of 5S rRNA and 3 proteins only: L5, L18, L25. A water-soluble carbodiimide [N-cyclohexyl-N'-(2-morpholinoethyl)-carbodiimide-methyl-p-toluolsulp honate] cross-links L18 to 5S rRNA at pH 7.2 and L25 to 5S rRNA at pH 7.7. This pH-dependence of cross-linked proteins is a consequence of the difference in stability of the initial complex: the complex has all three proteins at pH 7.7 but L18 mainly at pH 7.2. It has been shown that L18 stimulates the chemical modification of U87 and U89 residues of 5S rRNA by carbodiimide. A model of L18-5S rRNA complex has been proposed.


Ion-channel sensing of ferricyanide anion based on a supported bilayer lipid membrane.
Ferricyanide anion has usually been used as a marker of ion-channel sensors. In this work we first found that ferricyanide, itself, can act as a stimulus to regulate the permeability of sBLM prepared from didodecyldimethylammonium bromide (a kind of synthetic lipid) on a GC electrode. We used cyclic voltammetry and a.c. impedance to investigate this phenomenon. The interaction between sBLM and ferricyanide concerns time. Furthermore, we developed a sensor for ferricyanide anion. The ion-channel sensor is highly sensitive. It can detect ferricyanide concentration as low as 5 microM.


Communications: High-temperature water under pressure.
The effects of temperature and pressure upon structural, dynamical, and electronic properties of liquid H(2)O were systematically investigated via first principles molecular dynamics and in situ x-ray diffraction in the chosen isochore (1.00-1.61 g/cm(3)) and isotherm (300-900 K) conditions. Our study suggests that the crossover occurs between H-bonded and simple-liquidlike liquids by raising temperature in molecular liquid phase.


Relative replication fitness of multi-nucleoside analogue-resistant HIV-1 strains bearing a dipeptide insertion in the fingers subdomain of the reverse transcriptase and mutations at codons 67 and 215.
A two-serine insertion at position 69 (i69SS) of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) appears to be critical to enhance multi-nucleoside RT inhibitor resistance (MNR) in the sequence context of multiple zidovudine (AZT) resistance mutations (i.e., M41L, L210W, T215Y). In this study, we measured the replication capacity relative to the wild-type (WT) HIV-1 of a series of recombinant viruses carrying the i69SS in the background of a clinical isolate with MNR in which we introduced mutations D67N, Y215T, Y215S, or Y215N. In vitro measurements included replication kinetics and growth competition assays at different multiplicities of infection (MOI). While the addition of D67N had a minor effect on replication capacity, the reversion of Tyr-215 to Thr, Ser, or Asn was sufficient to increase the virus ability to replicate in a drug-free environment. The same genotypic changes at position 215 rendered the MNR virus susceptible to AZT and stavudine. Interestingly, the presence of the insertion together with mutation T215Y in an otherwise WT sequence background was not sufficient to confer high-level resistance to AZT, although its replication capacity was clearly impaired. Therefore, the RT residue 215 plays a critical role in both replication capacity and drug resistance of multidrug-resistant viruses containing the i69SS.


Influence of the spatial distribution of human hosts and large size containers on the dispersal of the mosquito Aedes aegypti within the first gonotrophic cycle.
It is generally accepted that Aedes aegypti (L.) (Diptera: Culicidae) has a short dispersal capacity, and that displacement can be influenced by the availability of oviposition sites in the surroundings of emergence or release sites. In the present article, we observed the influence of spatial heterogeneity of large containers and human hosts on the cumulative flight direction of Ae. aegypti females during the first gonotrophic cycle, testing the hypothesis that they aggregate in resource-rich areas, i.e. where there are higher concentrations of large containers and/or humans per habitation. We analysed data from pupal surveys and mark-release-recapture experiments (non-blood-fed females were released) carried out in two dengue endemic neighbourhoods of Rio de Janeiro, Brazil: Tubiacanga (a suburb, with a human density of 337 inhabitants/ha) and Favela do Amorim (a slum, with a human density of 901 inhabitants/ha). In both areas, host-seeking females of three different release cohorts showed an overall non-uniform and extensive dispersal from their release point within 1-2 days post-release. At 4-5 days post-release, when many of the released females would be expected to be gravid, in Tubiacanga most mosquitoes were collected in areas with a relatively higher density of containers/premise, independently of the density of residents/house, whereas in Favela do Amorim, almost half of the captured mosquitoes were collected in relatively resource-poorer areas. Although Ae. aegypti dispersal patterns varied between sites, overall the distances travelled from the release point and the cumulative flight directions were correlated with the density of containers and hosts, more markedly in Tubiacanga than in Favela do Amorim.


Rapid generation of detailed loss of heterozygosity profiles for routine diagnosis of gliomas.
Aberrations in the genomes of gliomas seem to correlate well with clinical parameters. Pertinent studies, however, rely on highly sophisticated methods, they require large amounts of high-quality sample material and/or they demand profound analytical expertise. Consequently, molecular tumour analysis has not yet been widely implemented in routine laboratory applications. We have developed an easy-to-perform approach for the rapid derivation of a detailed loss-of-heterozygosity profile from individual gliomas. DNA of PCR quality is extracted in a one-step procedure from routinely obtained material. A microsatellite-based marker set is used to detect the deletion status of genomic regions (i) with established diagnostic relevance, (ii) recurrently found deleted in gliomas, or (iii) generally associated with tumour suppressor activity. The complete profile comprises 25 regions and is generated from 64 markers multiplexed into 18 reactions. Illustratively, we present findings from an anaplastic oligodendroglioma; the molecular data for this tumour allow refined diagnostic and prognostic statements that could not be derived from histology alone. Our approach should prove useful in the routine diagnosis of gliomas. Simultaneously, research data for many highly relevant regions are generated in a comparatively simple and inexpensive way.


Primary ovarian insufficiency has strong familiality: results of a multigenerational genealogical study.
To determine the familiality of primary ovarian insufficiency (POI) at population level through examination of multigenerational genealogical information linked to electronic medical records. Case-control study. Not applicable. Women with POI were identified using International Classification of Disease 9 and 10 codes in electronic medical records (1995-2021) from 2 major health care systems in Utah and reviewed for accuracy. Cases were linked to genealogy information in the Utah Population Database (UPDB). All included POI cases (n = 396) were required to have genealogy information available for at least 3 generations of ancestors. The risk of POI in relatives was compared with population rates for POI matched by age, sex, and birthplace. Not applicable. Relative risk of POI in first-, second-, and third-degree relatives. We identified 396 validated cases of POI with an associated 2,132 first-degree relatives, 5,245 second-degree relatives, and 10,853 third-degree relatives. We found an increased risk of POI among the extended relatives of cases. Specifically, first-degree relatives demonstrated an 18-fold increased risk of POI compared with controls relative risk ([RR],18.52 95% confidence interval [CI], 10.12-31.07), second-degree relatives demonstrated a 4-fold increase (RR, 4.21; CI, 1.15-10.79), and third-degree relatives demonstrated a 2.7-fold increase (RR, 2.65; CI, 1.14-5.21]). This is the first population-based study to assess the familial clustering of POI. The data demonstrate excess familiality, familial clustering of POI in excess compared with matched population rates of disease, among first-, second-, and third-degree relatives. These findings support a genetic contribution to POI.


The alteration of autophagy and apoptosis in the hippocampus of rats with natural aging-dependent cognitive deficits.
The present study was aim to explore aging-dependent changes in hippocampal autophagy and apoptosis in a natural aging rat model from adult to old stages and to discover a suitable age for treating neurodegenerative diseases. Wistar rats at 5, 18 and 24months of age were used to mimic the adulthood, initial old, and old phases, respectively. The learning and cognitive ability of the rats was detected by the Morris water maze test. Morphological changes in the hippocampus were observed. Expressions of apoptosis and autophagy-related proteins were examined by Western blot. The adult group (5months) exhibited high levels of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II and cell survival, maintaining normal learning and cognitive function and integrated hippocampal morphology. The initial old group (18 months) presented a reduced number of neurons and cognitive deficits, and exhibited high levels of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to the adult group. The old group (24 months) exhibited a high level of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and a low level of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to its younger group, as well as significant neuronal death and cognitive deficits. The degree of autophagy was generally consistent with its negative regulator, the PI3K/Akt/mTOR axis, in all groups. Our data suggest that cognitive deficits are first observed in the initial old stage. The levels of autophagy and apoptosis tend to be opposite in the adult and old phases. High levels of autophagy and apoptosis coexist in the initial old stage. Our study indicates that up-regulation of autophagy in the initial old phase to anti-cognitive deficits must be further evaluated.


Kalman filtering-enhanced short-delay self-heterodyne interferometry for linewidth measurement.
We demonstrate an extended Kalman filtering-enhanced linewidth measurement in short-delay self-heterodyne interferometry (SDSHI). We found that a modified SDSHI trace closely resembles a biased cosine wave, which would enable convenient linewidth estimation by its uniform envelope contrast without any correction factor. Experimentally, we adopted this approach for kHz laser linewidth measurement, taking advantages of extended Kalman filtering (EKF) to adaptively track the cosine wave. Apart from the measurement noise suppression, this approach could use as many data points as possible in the noisy trace to make a linewidth estimation at each tracked data point, from which we can deduce valuable statistical parameters such as the mean and standard deviation. This approach involves no more equipment than conventional SDSHI and sophisticated EKF so that it can be easily implemented. Therefore, we believe it will find wide applications in ultra-narrow laser linewidth measurement.


Point-of-Care Sample Preparation and Automated Quantitative Detection of Schistosoma haematobium Using Mobile Phone Microscopy.
Schistosoma haematobium continues to pose a significant public health burden despite ongoing global control efforts. One of several barriers to sustained control (and ultimately elimination) is the lack of access to highly sensitive diagnostic or screening tools that are inexpensive, rapid, and can be used at the point of sample collection. Here, we report an automated point-of-care diagnostic based on mobile phone microscopy that rapidly images and identifies S. haematobium eggs in urine samples. Parasite eggs are filtered from urine within a specialized, inexpensive cartridge that is then automatically imaged by the mobile phone microscope (the "SchistoScope"). Parasite eggs are captured at a constriction point in the tapered cartridge for easy imaging, and the automated quantification of eggs is obtained upon analysis of the images by an algorithm. We demonstrate S. haematobium egg detection with greater than 90% sensitivity and specificity using this device compared with the field gold standard of conventional filtration and microscopy. With simple sample preparation and image analysis on a mobile phone, the SchistoScope combines the diagnostic performance of conventional microscopy with the analytic performance of an expert technician. This portable device has the potential to provide rapid and quantitative diagnosis of S. haematobium to advance ongoing control efforts.


The Risk of Venous Thromboembolism with Different Generation of Oral Contraceptives; a Systematic Review and Meta-Analysis.
Oral contraceptives (OCs) are considered as one of the most common risk factor of venous thromboembolism (VTE) in childbearing age. Some of the recent researches indicate that the odds of VTE may be even higher with newer generations of OCs. The present meta-analysis was designed to evaluate the effect of different generation of OCs on the occurrence of VTE. Two researchers independently ran a thorough search in Pubmed, ISI Web of Science, EMBASE, CINAHL and Scopus databases regarding study keywords including thromboembolic event, thromboembolism, embolism, thromboembolic, thrombotic and thrombosis, combined with oral contraceptive. The outcomes were the incidence of diagnosed thromboembolism, such as deep vein thrombosis, pulmonary embolism and cerebral venous thrombosis. Based on the heterogeneity of the studies, random effect model was used and pooled odds ratio was reported. Three cohort and 17 case-control studies with 13,265,228 subjects were entered into meta-analysis. Analysis showed that the odds of VTE in women taking OCs are more than three-fold (OR=3.13; 95% CI: 2.61-3.65). The risk of VTE in women taking first-, second- and third-generation OCs are 3.5 fold (OR=3.48; 95% CI: 2.01-4.94), 3 fold (OR=3.08; 95% CI: 2.43-3.74) and 4.3 fold (OR=4.35; CI: 3.69‒5.01), respectively. It seems that the risk of VTE is not same between different generations of OCs, so that third-generation has highest risk. Taking second and third-generation OCs increases the risk of VTE up to 3 and 4.3 fold, respectively. The researchers of the present study suggest that more trials be designed in relation to the effect of newer generations of OCs in different communities.


[Rheological therapeutic effects in diseases of the inner ear].
The aim of the rheological treatment in sudden deafness is the improvement of the microcirculation in the inner ear by hemodilution and decreased viscosity of the blood. Both parameters have been checked in two groups of patients suffering from sudden deafness; one treated with Dextran-40 and Pentoxifylline, the other with Dextran-40 only. Improvement of rheological characteristics of blood was statistically significant in the combined therapy with Dextran-40 and Pentoxifylline. Two cohorts of sudden deafness patients--one selected, one non selected--treated with Pentoxifylline and Dextran 40 have been evaluated in respect of hearing improvement under this rheological results compared with the spontaneous remission rate given by Weinaug in 1984.


Adaptation in brain glucose uptake following recurrent hypoglycemia.
Brain glucose metabolism is impaired during hypoglycemia, but, if sustained, brain metabolism reverts to normal in animal models--data in man are lacking. We tested the hypothesis that adaptations occur to allow maintenance of normal rates of brain glucose uptake (BGU) following recurrent hypoglycemia in man. Twelve normal humans were studied over 4 days. On the initial day, arterial plasma glucose concentrations were decreased from 4.72 to 2.50 mmol/liter in five 0.56 mmol/liter steps. Cerebral blood flow, brain arteriovenous glucose difference, BGU, and cognitive function were quantitated at each step. BGU was initially impaired at the 3.61 mmol/liter glucose step (P = 0.04) and was antedated by increments in epinephrine that began at 4.16 mmol/liter (P = 0.03). The onset of hypoglycemic symptoms occurred during the 3.61 mmol/liter glucose step (P = 0.02), whereas tests of cognitive function generally deteriorated at the 3.05 mmol/liter step (P < 0.05). During the next 56 hr, mean glucose concentrations were kept at 2.9 +/- 0.1 mmol/liter and reached normal only during meals. The stepped clamp protocol was repeated beginning at 4.16 mmol/liter on the last day. No decrement in BGU was observed at any step; cognitive function was preserved until significantly lower glucose concentrations on the final day relative to the first (P = 0.04). Subjects remained asymptomatic of hypoglycemia until they reached a glucose concentration of 2.50 mmol/liter (P < 0.001 vs. day 1), while initial increments in all counterregulatory hormones were forestalled to lower glucose steps than on day 1. Therefore, adaptations occur that allow normal BGU and cerebral function to be maintained during recurrent systemic hypoglycemia. Counterregulatory events that should result in symptoms of hypoglycemia and increments in endogenous glucose production are prevented until extremely subnormal glucose concentrations.


Unusual endoscopic and microscopic view of Enterobius vermicularis: a case report with a review of the literature.
Enterobius vermicularis has the broadest geographic range of any helminth and is the most common intestinal parasite seen in the primary care setting. Underappreciated is the fact that it is not always a benign disorder and could even cause life-threatening medical problems. Visualization of the actual worms during endoscopy is probably underappreciated in part because endoscopists have never actually seen the worm and/or are not actively looking for, or anticipating, worms. This report describes a case of worm infection as documented during colonoscopy and confirmed by microscopy. The gross and microscopic appearance of the worm is described. Literature regarding the wide range of gastrointestinal and nongastrointestinal manifestations, including potentially life-threatening illnesses, as well as treatment options, are also reviewed.


Brain tumors in eloquent areas: A European multicenter survey of intraoperative mapping techniques, intraoperative seizures occurrence, and antiepileptic drug prophylaxis.
Intraoperative mapping and monitoring techniques for eloquent area tumors are routinely used world wide. Very few data are available regarding mapping and monitoring methods and preferences, intraoperative seizures occurrence and perioperative antiepileptic drug management. A questionnaire was sent to 20 European centers with experience in intraoperative mapping or neurophysiological monitoring for the treatment of eloquent area tumors. Fifteen centers returned the completed questionnaires. Data was available on 2098 patients. 863 patients (41.1%) were operated on through awake surgery and intraoperative mapping, while 1235 patients (58.8%) received asleep surgery and intraoperative electrophysiological monitoring or mapping. There was great heterogeneity between centers with some totally AW oriented (up to 100%) and other almost totally ASL oriented (up to 92%) (31% SD). For awake surgery, 79.9% centers preferred an asleep-awake-asleep anesthesia protocol. Only 53.3% of the centers used ECoG or transcutaneous EEG. The incidence of intraoperative seizures varied significantly between centers, ranging from 2.5% to 54% (p < 0.001). It there appears to be a statistically significant link between the mastery of mapping technique and the risk of intraoperative seizures. Moreover, history of preoperative seizures can significantly increase the risk of intraoperative seizures (p < 0.001). Intraoperative seizures occurrence was similar in patients with or without perioperative drugs (12% vs. 12%, p = 0.2). This is the first European survey to assess intraoperative functional mapping and monitoring protocols and the management of peri- and intraoperative seizures. This data can help identify specific aspects that need to be investigated in prospective and controlled studies.


American Brachytherapy Task Group Report: Adjuvant vaginal brachytherapy for early-stage endometrial cancer: A comprehensive review.
This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the postoperative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early-stage endometrial cancer patients results in very low rates of vaginal recurrence (0-3.1%) with low rates of late toxicity which are primarily vaginal in nature. Post-Operative Radiation Therapy in Endometrial Cancer 2 (PORTEC-2) supports that VBT results in noninferior rates of vaginal recurrence compared to external beam radiotherapy for the treatment of high-intermediate risk patients. VBT as a boost after external beam radiotherapy, in combination with chemotherapy, and for high-risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians prefer joint decision making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multidisciplinary setting, and patients should be counseled properly regarding the risks and benefits of adjuvant therapy.


Everyday life in breast cancer survivors experiencing challenges: A qualitative study.
Early diagnosis and treatment of breast cancer results in an increasing number of survivors, some of whom face new challenges in their transition to daily life. Based on these experiences, the aim of this study was to describe the everyday life in breast cancer survivors experiencing challenges. Eleven women recruited from a follow-up study of breast cancer patients participated in qualitative interviews about their everyday occupations seven years after ending treatment. The inductive analysis revealed ten categories that were organized into five subthemes under the two main themes 'bodily and mental loneliness' and 'new center of gravity in everyday life'. Findings showed how relevant information and guidance; active support to the client and their relatives; and a balance between occupations at home and at work were important matters to handle their everyday life challenges. By assisting these women in finding new patterns of meaningful occupations that positively affect their everyday life, the study suggests some central elements to be included in future follow-up practice for breast cancer survivors. Approaching this goal, occupational therapists should contribute to more involvement assisting cancer survivors and their partners in finding new patterns of meaningful occupations that positively affect their everyday life.