Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats.

Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.

High-resolution spectroscopy of Lambda16N by electroproduction.

An experimental study of the (16)O(e,e'K(+))(Lambda)(16)N reaction has been performed at Jefferson Lab. A thin film of falling water was used as a target. This permitted a simultaneous measurement of the p(e,e'K(+))Lambda, Sigma(0) exclusive reactions and a precise calibration of the energy scale. A ground-state binding energy of 13.76+/-0.16 MeV was obtained for (Lambda)(16)N with better precision than previous measurements on the mirror hypernucleus (Lambda)(16)O. Precise energies have been determined for peaks arising from a Lambda in s and p orbits coupled to the p(1/2) and p(3/2) hole states of the (15)N core nucleus.

High resolution spectroscopy of (lambda)(12)B by electroproduction.

An experiment measuring electroproduction of hypernuclei has been performed in hall A at Jefferson Lab on a 12C target. In order to increase counting rates and provide unambiguous kaon identification two superconducting septum magnets and a ring imaging Cherenkov detector were added to the hall A standard equipment. An unprecedented energy resolution of less than 700 keV FWHM has been achieved. Thus, the observed (Lambda)(12)B spectrum shows for the first time identifiable strength in the core-excited region between the ground-state s-wave Lambda peak and the 11 MeV p-wave Lambda peak.

Self-reported stress reactivity and psoriasis-related stress of Nordic psoriasis sufferers.

OBJECTIVES: The purpose of the study was to investigate the perceived influence of stress on psoriasis onset and disease severity in a large sample of psoriatics and to compare stress reactors and non-reactors with respect to psoriasis-related stress, disease severity, family history of psoriasis and sociodemographic factors. PATIENTS/METHODS: A total of 5795 members of the Nordic psoriasis associations and 702 patients recruited from Nordic dermatologists or university clinics were asked whether their first outbreak of psoriasis occurred during times of worry and stress. They were also asked to rate the degree to which their psoriasis was influenced by stress and to complete the Psoriasis Life Stress Index, the Psoriasis Disability Index and a number of additional questions concerning sociodemographic factors. RESULTS: Seventy-one per cent of the members and 66% of the patients reported that their psoriasis was exacerbated by stress, and 35% in both groups reported that the onset of their psoriasis occurred during a time of worry and stress. Stress reactors, scoring above the median on stress reactivity, reported greater disease severity, psoriasis-related stress and impairment of disease-related quality of life. They also reported more frequent use of tobacco, tranquillizers and antidepressants. More women than men were stress reactors, and stress reactors were more likely to have a family history of psoriasis. CONCLUSION: Our findings confirm and extend the results of previous studies and indicate that a subgroup of psoriatics may be more psychologically reactive to their disease and its influence on everyday life. Whether this group is also physiologically more reactive to psychosocial stress remains to be investigated.

Quality of life in 6497 Nordic patients with psoriasis.

BACKGROUND: Disease-specific psoriasis-related quality of life (QOL) measures have recently been developed and used in several hospital-based investigations. However, little is known about the impact of psoriasis on QOL in people with psoriasis who are not referred by dermatologists. OBJECTIVES: The purpose of the study was to investigate psoriasis-related QOL in a large sample of members of the psoriasis associations from the Nordic countries, and to compare the results with those from psoriasis patients recruited from Nordic dermatologists or Nordic University clinics. PATIENTS AND METHODS: A total of 5795 association members and 702 patients rated their psoriasis severity and completed the Psoriasis Disability Index and the Psoriasis Life Stress Index. RESULTS: Patients reported greater disease severity and greater impairment of QOL than members of associations, and Norwegian participants reported greater disease severity and greater impairment of QOL than participants from the remaining Nordic countries. Older and married participants reported less impairment of QOL than younger participants and those living alone. When controlling for the influence of these and other demographic and socio-economic factors, self-reported severity emerged as the most significant predictor of psoriasis-related QOL, explaining 32-26% of the variation in QOL scores, with the remaining factors only accounting for 4-5% of the variation. Although correlated with self-reported severity, Psoriasis Area and Severity Index scores were not a significant predictor of QOL in the patient sample. CONCLUSIONS: Though self-reported severity may be the most important predictor, further research is needed to determine factors explaining the remaining variance in psoriasis-related QOL.

A transcriptional roadmap to wood formation.

The large vascular meristem of poplar trees with its highly organized secondary xylem enables the boundaries between different developmental zones to be easily distinguished. This property of wood-forming tissues allowed us to determine a unique tissue-specific transcript profile for a well defined developmental gradient. RNA was prepared from different developmental stages of xylogenesis for DNA microarray analysis by using a hybrid aspen unigene set consisting of 2,995 expressed sequence tags. The analysis revealed that the genes encoding lignin and cellulose biosynthetic enzymes, as well as a number of transcription factors and other potential regulators of xylogenesis, are under strict developmental stage-specific transcriptional regulation.

Treatment of psoriasis in the Nordic countries: a questionnaire survey from 5739 members of the psoriasis associations data from the Nordic Quality of Life Study.

The data from a questionnaire-based study of 5,739 members of the psoriasis associations of Denmark, Finland, Iceland, Norway, Sweden and the Faeroe Islands showed that the two most commonly used active agents were topical steroids (89.7% total use and 49.4% present use) and calcipotriol (73.1% total use and 35.8% present use), with only small variations between the countries. Marked differences between the countries were, however, found within all other types of psoriasis therapy, including the so-called alternative treatments. Significant priorities varied between the different countries. The use of dithranol in Finland was almost twice the average. While 14.2% of Danish members had received grenz-rays within the last week only 0.1% of the Finns had been given the same treatment. Psoralen plus ultraviolet A (PUVA) was being used by 13.1% of the Finnish psoriatics compared with 3.8% of Danes, while PUVA was almost non-existent on the Faeroe Islands. The use of non-PUVA phototherapy was highest in Norway and Sweden. Almost 10% of the Danes were presently on methotrexate, which was used far more than etretinate/acitretin or cyclosporine. In contrast, Finnish patients more often received etretinate than other systemic agents, and in Iceland there was a higher present use of cyclosporine than of etretinate. The popularity of alternative therapies was highest in Iceland, where 26.6% had taken such medication during the last week. The results of the study suggest that different treatment patterns should be taken into consideration when discussing the prognosis of psoriasis in different countries.

[Functional evaluation of heart failure patients in primary care. The NYHA system is unreliable since intercurrent illness can give rise to similar symptoms]. / Funktionsvärdering av hjärtsviktspatienter i primärvården. NYHA-systemet opålitlight då annan sjukdom ger liknande symtombild.

A group of 158 patients with congestive heart failure was studied in detail concerning other types of morbidity. The purpose was to evaluate how often classification according to the NYHA system was disturbed by intercurrent disease with a similar set of symptoms. At the same time, a visual analogue scale for the evaluation of physical capacity was tested. Seventy-eight per cent of the patients had intercurrent disease putting them at risk of inadequate NYHA classification. There was no correlation between the patients' NYHA class and grade or type of echocardiographic ventricular dysfunction. However there was a correlation between NYHA class and the presence of intercurrent disease.

Recognising pain in older adults living in sheltered accommodation: the views of nurses and older adults.

Sixty-six randomly selected older adults and their contact nurses participated in interviews based on standardised assessments of pain and open-ended questions focusing how pain was expressed and recognised. The sample included older adults with normal as well as cognitively impaired function. Seventy-nine percent of older adults with normal cognition were often in pain. Contact nurses assessed pain in 57% of cognitively impaired older adults. The content in the statements showed that pain recognition was a communicative interactive process based on verbal and non-verbal expressions. The process comprised attempts to understand the cause and intention of the expression and to verify the presence of pain. Changes in mood, facial expressions and physiological responses were described less often by older adults than by their nurses. Contact nurses of cognitively impaired older adults judged immobility as the source of pain, that it was possible to see when the person was in pain and that pain was expressed by paralinguistic and body language more often than contact nurses of cognitively healthy older adults. Characteristics of nurses and older adults could facilitate or hinder pain recognition. The findings indicate a need for reflective discussions in the staff group focusing on how to perform systematic assessments of verbal and non-verbal expressions and of hindrances and facilitators for recognising pain in older adults.

Functional domains of yeast plasmid-encoded Rep proteins.

Both of the Saccharomyces cerevisiae 2 microm circle-encoded Rep1 and Rep2 proteins are required for efficient distribution of the plasmid to daughter cells during cellular division. In this study two-hybrid and in vitro protein interaction assays demonstrate that the first 129 amino acids of Rep1 are sufficient for self-association and for interaction with Rep2. Deletion of the first 76 amino acids of Rep1 abolished the Rep1-Rep2 interaction but still allowed some self-association, suggesting that different but overlapping domains specify these interactions. Amino- or carboxy-terminally truncated Rep1 fusion proteins were unable to complement defective segregation of a 2 microm-based stability vector with rep1 deleted, supporting the idea of the requirement of Rep protein interaction for plasmid segregation but indicating a separate required function for the carboxy-terminal portion of Rep1. The results of in vitro baiting assays suggest that Rep2 contains two nonoverlapping domains, both of which are capable of mediating Rep2 self-association. The amino-terminal domain interacts with Rep1, while the carboxy-terminal domain was shown by Southwestern analysis to have DNA-binding activity. The overlapping Rep1 and Rep2 interaction domains in Rep1, and the ability of Rep2 to interact with Rep1, Rep2, and DNA, suggest a model in which the Rep proteins polymerize along the 2 microm circle plasmid stability locus, forming a structure that mediates plasmid segregation. In this model, competition between Rep1 and Rep2 for association with Rep1 determines the formation or disassembly of the segregation complex.

[Diagnosis and treatment of heart failure in primary health care. Low correlation between Pro-ANF and heart failure]. / Diagnostik och behandling av hjärtsvikt i primärvården. Låg korrelation mellan Pro-ANF och hjärtsvikt.

Three eastern Swedish primary care clinics serving a predominantly rural clientele monitored for 13 months all patients under 80 years of age with a diagnosis based on clinical signs alone of heart failure (n = 56) or suspected incipient heart failure (n = 62). Echocardiography was performed on all patients. For 64% of the former group, the putative diagnosis matched echocardiography findings. Results showed a purely diastolic disorder in one-fifth of all 118 patients, and a hemodynamically significant, hitherto unknown heart defect in about as many. Pro-ANF assays correlated poorly with manifest heart failure. Pharmacological treatments were registered, and at 6-month follow-up, 82% of patients with systolic failure were receiving ACE-inhibition.

Pain in older adults living in sheltered accommodation--agreement between assessments by older adults and staff.

This study aimed to investigate the presence of pain, pain duration, localization(s), intensity, type and pharmacological treatment among older adults living in sheltered accommodation or receiving rehabilitation, as well as the agreement between pain assessments performed by staff and the older adults. Twenty-nine randomly selected older adults (65+ years) and the staff who looked after them participated in a structured interview based on standardized measures for pain assessment and physical, intellectual and communicative functions. Pain was found to be common, with a majority of participants experiencing it every day or all of the time. Nine out of 22 of the older adults in pain had no pain relief drugs at all. Agreement between assessments by the older adults and the staff was no higher than moderate and in general pain levels were underestimated. The findings indicate that older adults were at risk of undetected and untreated pain and the risk was even higher for those with speech difficulties. The provision of good nursing care for older adults in sheltered accommodation requires systematic routines for frequent pain assessments.

Validation of air tonometric measurement of gastric regional concentrations of CO2 in critically ill septic patients.

OBJECTIVE: To evaluate the accuracy of continuous air tonometry (Tonocap, Tonometric Division, Instrumentarium, Helsinki, Finland). DESIGN: The accuracy of air tonometry was tested by comparing it with conventional saline tonometry in mechanically ventilated, critically ill septic patients and in vitro determining the partial pressure of carbon dioxide (PCO2) of humidified gases with known concentrations of CO2. SETTING: A mixed intensive care unit in a university hospital. PATIENTS: 16 mechanically ventilated patients with sepsis. MEASUREMENTS AND RESULTS: Two gastric tonometer catheters (TRIP NGS catheter, Tonometric Division, Instrumentarium, Helsinki, Finland) were introduced into the patients' stomachs. The control catheter was used as a conventional saline tonometer and the other catheter was used with the Tonocap monitoring device. A total of 153 paired measurements was made and analysed according to Bland and Altman. The mean difference between air PCO2 and saline PCO2 values (bias), the standard deviation of the differences (precision), and the Pearson correlation coefficient between air PCO2 and saline PCO2 were calculated. The data on patients were pooled and calculated for different cycle times. The mean bias (kPa) was-0.02 with a 10-min cycle time, 0.31 with 15 min, 0.56 with 30 min and 0.21 with 60-min. The precisions were 0.39, 0.54, 0.44 and 0.76, respectively. Pearson correlation coefficients were 0.93, 0.97, 0.95 and 0.82, respectively (p < 0.0001). In vitro tonometry with the Tonocap was performed in a gas chamber fully saturated with known CO2 concentrations. The clinically important 10-min cycle time was tested with 5 Tonocap monitors. Except for the first 10-min cycle time, PCO2 values determined by the Tonocap monitoring systems were comparable to known CO2 concentrations. CONCLUSIONS: The accuracy of Tonocap continuous air tonometry is close to that of conventional saline tonometry. Moreover, the clinically important 10-min cycle time with air tonometry correlated very well with saline tonometry and the time response with air tonometry was short.

[Simplified ambulatory treatment of thrombosis. A daily dosage of subcutaneous low-molecular-weight heparin]. / Förenklad trombosbehehandling iöppen vård. Lågmolekylärt heparin subkutant i en daglig dos.

Of 162 patients aged 27-28 years, referred during a 12-month period to the Dept. of medicine, Norrköping Central Hospital, for deep vein thrombosis (DVT), 102 (63 per cent) were treated as out-patients with the low molecular weight heparin preparation, dalteparin (Fragmin), given subcutaneously at a standardised daily dosage of 200 U/kg. No serious thrombotic events were reported. The frequency of post-thrombotic symptoms at six months did not differ from that among hospitalised patients on standard heparin treatment. Thus, the proportion of DVT patients treated as in-patients was reduced by 50 per cent, despite a 33 per cent increase in the number of referrals for DVT during the period. At follow-up, almost 90 per cent of the patients expressed satisfaction with the out-patient routines.

Structural elements in yeast tRNAs required for homologous modification of guanosine-26 into dimethylguanosine-26 by the yeast Trm1 tRNA-modifying enzyme.

In eukaryotic tRNAs, guanosines in position 26 (G26), located at the junction between the D-stem and the anticodon stem of tRNA, are usually modified to N2,N2-dimethylguanosine (m2(2)G). Although G26 is a prerequisite for biosynthesis of m2(2)G26, it is not self-sufficient for the formation of the dimethylated G26, since in exceptional cases eukaryotic tRNAs have an unmodified G26. In the yeast Saccharomyces cerevisiae the only tRNA species with an unmodified G26 is tRNAAsp. Using in vitro transcripts of this tRNA, as well as of yeast tRNAPhe, a tRNA containing m2(2)G26 in vivo, we have investigated the requirements on tRNA sequences and structures for the formation of m2(2)G26 by the yeast enzyme, i.e. in a homologous in vitro system. We have now demonstrated that G26 was efficiently dimethylated in vitro also after deletion of the entire anticodon stem and loop. We conclude that the elements necessary for a productive interaction between G26 in nuclear coded yeast tRNAs and the yeast G26 modifying enzyme are located within the core of the tRNA. For modification of G26 to m2(2)G26 via monomethylated G26, important primary and secondary structural elements in the tRNAs are a size of at least five nucleotides in the variable loop together with two G-C base pairs in the D-stem. This is the first case reported where the minimal requirements on nuclear coded tRNAs for a yeast modifying enzyme has been elucidated.

Characterization of the genes of the 2,3-butanediol operons from Klebsiella terrigena and Enterobacter aerogenes.

The genes involved in the 2,3-butanediol pathway coding for alpha-acetolactate decarboxylase, alpha-acetolactate synthase (alpha-ALS), and acetoin (diacetyl) reductase were isolated from Klebsiella terrigena and shown to be located in one operon. This operon was also shown to exist in Enterobacter aerogenes. The budA gene, coding for alpha-acetolactate decarboxylase, gives in both organisms a protein of 259 amino acids. The amino acid similarity between these proteins is 87%. The K. terrigena genes budB and budC, coding for alpha-ALS and acetoin reductase, respectively, were sequenced. The 559-amino-acid-long alpha-ALS enzyme shows similarities to the large subunits of the Escherichia coli anabolic alpha-ALS enzymes encoded by the genes ilvB, ilvG, and ilvI. The K. terrigena alpha-ALS is also shown to complement an anabolic alpha-ALS-deficient E. coli strain for valine synthesis. The 243-amino-acid-long acetoin reductase has the consensus amino acid sequence for the insect-type alcohol dehydrogenase/ribitol dehydrogenase family and has extensive similarities with the N-terminal and internal regions of three known dehydrogenases and one oxidoreductase.

Efficacy and safety of itraconazole in the long-term treatment of onychomycosis.

Sixty-one patients with a clinical diagnosis of onychomycosis in finger or toe nails were treated with itraconazole 100 mg/day or griseofulvin 500 mg/day for six to nine months. The infective causes were Trichophyton rubrum, Trichophyton mentagrophytes, or Trichophyton violaceum, and in two cases Candida albicans. A total of 27 finger and 390 toe nails were infected. Statistically significant intragroup reductions from baseline symptom severity values were seen at endpoint (month 6 or 9) for both treatment groups for all parameters: colour change, thickness, brittleness and unaffected area. No clinically or statistically significant differences between the treatment groups were seen at endpoint. However, the itraconazole group continued to improve during the follow-up, while the mean symptom severity ratings remained the same in the griseofulvin group. All itraconazole patients and 85% of griseofulvin patients were rated as cured or markedly improved at endpoint. Nineteen out of 26 evaluable itraconazole patients (73%) remained cured during the three month follow-up period, compared with 12 out of 17 griseofulvin patients (71%). The rather large number of drop-outs, especially among griseofulvin patients, makes it difficult to draw definitive conclusions of the symptom recurrence. Two itraconazole patients stopped medication due to an adverse event, compared to four patients in the griseofulvin group. The clinical laboratory data on itraconazole-treated patients did not show any statistically or clinically significant changes. In conclusion, itraconazole was at least as effective as griseofulvin in the treatment of onychomycosis. The itraconazole group continued to improve after the treatment was stopped. The results show that itraconazole 100 mg/day is safe and efficient in the long-term treatment of fungal nail infections.

Chromosomal Integration and Expression of Two Bacterial alpha-Acetolactate Decarboxylase Genes in Brewer's Yeast.

A bacterial gene encoding alpha-acetolactate decarboxylase, isolated from Klebsiella terrigena or Enterobacter aerogenes, was expressed in brewer's yeast. The genes were expressed under either the yeast phosphoglycerokinase (PGK1) or the alcohol dehydrogenase (ADH1) promoter and were integrated by gene replacement by using cotransformation into the PGK1 or ADH1 locus, respectively, of a brewer's yeast. The expression level of the alpha-acetolactate decarboxylase gene of the PGK1 integrant strains was higher than that of the ADH1 integrants. Under pilot-scale brewing conditions, the alpha-acetolactate decarboxylase activity of the PGK1 integrant strains was sufficient to reduce the formation of diacetyl below the taste threshold value, and no lagering was needed. The brewing properties of the recombinant yeast strains were otherwise unaltered, and the quality (most importantly, the flavor) of the trial beers produced was as good as that of the control beer.