A randomised assessment of the use of a quality of life questionnaire with or without intervention in patients attending a thoracic cancer clinic.

The study examined the impact of using a quality of life (QoL) questionnaire during a clinic to identify QoL issues and to improve QoL. 138 patients were randomised (1:1:1) to either (1) an Intervention group that completed the European Organisation for Research and Treatment of Cancer-Core Quality of Life Questionnaire and Lung Cancer Module (EORTC QLQ-C30 and LC13) at baseline and received feedback during a clinic, (2) an Attention group that completed the questionnaire at baseline without feedback and (3) a Control group that did not complete the questionnaire. All patients completed the same questionnaire 6 weeks later and a contact diary during the study period. There was a significant difference between the Intervention and Control groups for the mean number of QoL issues identified at baseline (4.69 vs. 2.81, P = 0.006) and the mean number of actions taken (4.41 vs. 2.46, P = 0.004). At 6 weeks, there was no difference between the groups in global QoL (Intervention vs. Control group, P = 0.596; Attention vs. Control, P = 0.973). The results suggest that the completion of the EORTC QLQ-C30 LC13 with feedback improves communication and increases the number of QoL issues identified and actions taken. However, the intervention does not impact on QoL per se. Clinicaltrials.gov: NCT01213745.

Rapid point-of-care detection of SARS-CoV-2 infection in exhaled breath using ion mobility spectrometry: a pilot study.

BACKGROUND: An effective testing strategy is essential for pandemic control of the novel Coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Breath gas analysis can expand the available toolbox for diagnostic tests by using a rapid, cost-beneficial, high-throughput point-of-care test. We conducted a bi-center clinical pilot study in Germany to evaluate breath gas analysis using multi-capillary column ion mobility spectrometry (MCC-IMS) to detect SARS-CoV-2 infection. METHODS: Between September 23, 2020, and June 11, 2021, breath gas measurements were performed on 380 patients (SARS-CoV-2 real-time polymerase chain reaction (PCR) positive: 186; PCR negative: 194) presenting to the emergency department (ED) with respiratory symptoms. RESULTS: Breath gas analysis using MCC-IMS identified 110 peaks; 54 showed statistically significant differences in peak intensity between the SARS-CoV-2 PCR-negative and PCR-positive groups. A decision tree analysis classification resulted in a sensitivity of 83% and specificity of 86%, but limited robustness to dataset changes. Modest values for the sensitivity (74%) and specificity (52%) were obtained using linear discriminant analysis. A systematic search for peaks led to a sensitivity of 77% and specificity of 67%; however, validation by transferability to other data is questionable. CONCLUSIONS: Despite identifying several peaks by MCC-IMS with significant differences in peak intensity between PCR-negative and PCR-positive samples, finding a classification system that allows reliable differentiation between the two groups proved to be difficult. However, with some modifications to the setup, breath gas analysis using MCC-IMS may be a useful diagnostic toolbox for SARS-CoV-2 infection. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on September 21, 2020 (NCT04556318; Study-ID: HC-N-H-2004).

Effects of breeding at the second oestrus or after post-weaning hormonal treatment with altrenogest on subsequent reproductive performance of primiparous sows.

This study investigated the effects of breeding at the second oestrus after weaning or after feeding an orally active progestagen (altrenogest) on the subsequent reproductive performance of primiparous sows. After 3 weeks of lactation, 663 weaned sows of two genotypes were allocated into three groups: G1--breeding at the first oestrus after weaning; G2--breeding at the second oestrus after weaning and G3--treatment with altrenogest for 5 days after weaning and breeding at the first oestrus after the end of the treatment. Body weight at breeding was lower in G1 and G3 than in G2 sows (p < 0.05). The interval to show oestrus was similar for G1 and G2 groups (p > 0.05) but higher (p < 0.05) than that observed in G3 group. Within genotype A, percentages of females in oestrus within 10 days were not different (p > 0.05) among groups, whereas in genotype B, more G1 and G2 sows (p < 0.05) showed oestrus than G3 sows. In both genotypes, lower farrowing rates were observed in G3 than in G1 and G2 sows (p < 0.05) and a greater litter size (p < 0.05) was observed in G2 sows. In genotype A, the number of total born piglets was similar for G1 and G3 groups (p > 0.05), whereas in genotype B, G1 sows had a greater litter size than G3 sows (p < 0.05). Body weight at weaning and at breeding was similar (p > 0.05) between farrowed and non-farrowed sows in all groups. Reproductive performance is not improved in primiparous sows treated with altrenogest during 5 days after weaning. The reproductive performance of genotype B sows is compromised in Control and Altrenogest-treated sows but not in those bred at the second oestrus after mating. Breeding at the second oestrus after weaning allows primiparous sows to gain weight between weaning and service, and increases their farrowing rate and subsequent litter size.

Yeast cell cycle protein CDC48p shows full-length homology to the mammalian protein VCP and is a member of a protein family involved in secretion, peroxisome formation, and gene expression.

Yeast mutants of cell cycle gene cdc48-1 arrest as large budded cells with microtubules spreading aberrantly throughout the cytoplasm from a single spindle plaque. The gene was cloned and disruption proved it to be essential. The CDC48 sequence encodes a protein of 92 kD that has an internal duplication of 200 amino acids and includes a nucleotide binding consensus sequence. Vertebrate VCP has a 70% identity over the entire length of the protein. Yeast Sec18p and mammalian N-ethylmaleimide-sensitive fusion protein, which are involved in intracellular transport, yeast Pas1p, which is essential for peroxisome assembly, and mammalian TBP-1, which influences HIV gene expression, are 40% identical in the duplicated region. Antibodies against CDC48 recognize a yeast protein of apparently 115 kD and a mammalian protein of 100 kD. Both proteins are bound loosely to components of the microsomal fraction as described for Sec18p and N-ethylmaleimide-sensitive fusion protein. This similarity suggests that CDC48p participates in a cell cycle function related to that of N-ethylmaleimide-sensitive fusion protein/Sec18p in Golgi transport.

The ins and outs of Raf kinases.

Raf kinases are signal-integrating enzymes that have the ability to switch tyrosine kinase signalling to serine/threonine phosphorylation and connect growth factor receptors with transcription factors. The connection involves a cascade of protein kinases that is essential for cellular proliferation and differentiation of species ranging from worms to humans. This cascade also mediates transformation by most oncogenes.

Palosuran inhibits binding to primate UT receptors in cell membranes but demonstrates differential activity in intact cells and vascular tissues.

BACKGROUND AND PURPOSE: The recent development of the UT ligand palosuran (1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulphate salt) has led to the proposition that urotensin-II (U-II) plays a significant pathological role in acute and chronic renal injury in the rat. EXPERIMENTAL APPROACH: In the present study, the pharmacological properties of palosuran were investigated further using a series of radioligand binding and functional bioassays. KEY RESULTS: Palosuran functioned as a 'primate-selective' UT ligand in recombinant cell membranes (monkey and human UT K(i) values of 4 +/- 1 and 5 +/- 1 nM), lacking appreciable affinity at other mammalian UT isoforms (rodent and feline K(i) values >1 microM). Paradoxically, however, palosuran lost significant (10- to 54-fold) affinity for native and recombinant human UT when radioligand binding was performed in intact cells (K(i) values of 50 +/- 3 and 276 +/- 67 nM). In accordance, palosuran also exhibited diminished activity in hUT (human urotensin-II receptor)-CHO (Chinese hamster ovary) cells (IC50 323 +/- 67 nM) and isolated arteries (K(b)>10 microM in rat aorta; K(b)>8.5 microM in cat arteries; K(b)>1.6 microM in monkey arteries; K(b) 2.2 +/- 0.6 microM in hUT transgenic mouse aorta). Relative to recombinant binding K(i) values, palosuran was subjected to a 392- to 690-fold reduction in functional activity in monkey isolated arteries. Such phenomena were peculiar to palosuran and were not apparent with an alternative chemotype, SB-657510 (2-bromo-N-[4-chloro-3-((R)-1-methyl-pyrrolidin-3-yloxy)-phenyl]-4,5-dimethoxybenzenesulphonamide HCl). CONCLUSIONS AND IMPLICATIONS: Collectively, such findings suggest that caution should be taken when interpreting data generated using palosuran. The loss of UT affinity/activity observed in intact cells and tissues cf. membranes offers a potential explanation for the disappointing clinical efficacy reported with palosuran in diabetic nephropathy patients. As such, the (patho)physiological significance of U-II in diabetic renal dysfunction remains uncertain.

The ATPase activity of purified CDC48p from Saccharomyces cerevisiae shows complex dependence on ATP-, ADP-, and NADH-concentrations and is completely inhibited by NEM.

The cell cycle protein CDC48p from Saccharomyces cerevisiae is a member of a protein superfamily (AAA superfamily) characterized by a common region of approximately 200 amino-acid residues including an ATP binding consensus. CDC48p purified to homogeneity showed considerable ATPase activity which could be completely abolished by preincubation with NEM in the absence of ATP. ATP protects the protein from NEM and stabilizes the otherwise labile enzyme. The ATPase activity is reversibly inhibited by NADH and shows cooperativity with its substrate ATP. The application of the in vitro ATPase activity to the identification of physiologically interacting molecules is discussed. By electron microscopy, the enzyme was shown to consist of hexameric ring structures similar to its vertebrate homologue.

Choice of peptide and peptide length for the generation of antibodies reactive with the intact protein.

N-terminal peptides of bovine ribonuclease (RNase) of 20, 13 and 7 amino acid residues were isolated by reversed-phase high-performance liquid chromatography (HPLC). Antibodies were raised in mice against these peptides coupled to bovine serum albumin (BSA). It was shown that antibodies against the peptides reacted with the intact protein and that the immune response decreased with decreasing size of peptide. In order to obtain a satisfactory reaction with the intact protein, the peptide immunogen should be longer than 7 amino acids.

Localisation of hyaluronate (HA) in primary tumors and nude mouse xenografts of human pancreatic carcinomas using a biotinylated HA-binding protein.

A biotinylated hyaluronate (HA)-binding protein isolated from bovine cartilage was used to analyze the distribution of HA in nude mouse xenografts derived from human pancreatic adenocarcinoma cell lines as well as in primary human pancreatic adenocarcinomas. The most reproducible results for the localisation of HA were obtained using cryostat sections. When the biotinylated HA-binding protein was applied to histological sections of nude mouse xenografts, the specific staining found could be inhibited by preincubating the HA-binding protein with an excess of HA or by hyaluronidase treatment of the tissue before staining. The highest HA concentration was found at the tumor boundaries, while in the central part of the tumor staining was slight or absent. In cryostat sections of primary tumors HA was found predominantly in the connective tissue immediately around tumor cells or at the border between the tumor and normal pancreatic tissue.

[Contraceptive pill amenorrhea--does it exist?]. / P-pilleramenorré - finns den?

PIP: The possibility of amenorrhea as a direct result of discontinuing oral contraceptives is discussed and its etiology is explored. In a study of 1860 women in Uppsala county in Sweden, 16% of the amenorrhea cases among these women could be temporally related to the discontinuation of oral contraceptive use. Earlier irregularities of menstruation and psychological stress are discussed as indications that "contraceptive pill amenorrhea" could occur. Loss of weight, often combined with symptoms of anorexia nervosa, is also a frequent indication of susceptibility to "contraceptive pill amenorrhea." The possibility of "contraceptive pill amenorrhea" as an iatrogenic syndrome is discussed.^ieng

Behaviour and growth performance of low-birth-weight piglets cross-fostered in multiparous sows with piglets of higher birth weights / Comportamento e desempenho de crescimento de leitões com baixo peso ao nascer uniformizados com leitões de maior peso em fêmeas suínas multíparas

The aim of the study was to evaluate the behaviour, pre-weaning survival rate and growth performance of low birth weight (BW) piglets cross-fostered with piglets of higher weights. Piglets were transferred to 60 foster sows, and divided in three groups (G; n=20): G1- 12 low BW piglets (0.80 - 1.25kg); G2- six low BW piglets and six intermediate BW piglets (1.40 - 1.60kg), and G3- six low BW piglets and six high BW piglets (>1.70kg). For the analysis, groups G2 and G3 were subdivided in LG2 (six G2 light piglets); IG2 (six G2 intermediate piglets), LG3 (six G3 light piglets), and HG3 (six G3 heavy piglets). Behavioural observations were carried out on days 1, 2, 4 and 6 (visual direct observation) and on days 3 and 5 (video recording) after birth. The percentage of missed nursings was higher in LG3 piglets than in LG1, IG2 and HG3 piglets, on days 1 and 2. On day 4, light piglets (LG1, LG2 and LG3) missed more nursings than IG2 and HG3 piglets. On day 3, video recording showed a higher percentage of missed nursings in LG1, LG2, and LG3 piglets as compared to HG3 piglets. On day 1, the number of fights during nursing was higher in IG2 than in LG1 and LG3 piglets. Also on day 1, number of fights and percentage of piglets engaged in fights, during 15min after nursing, were higher in LG1, LG3 and HG3 than in LG2 piglets. More playful behaviours were observed on day 2 in IG2 and HG3 piglets compared to LG1, LG2 and LG3 piglets. Light piglets (LG1, LG2, and LG3) presented similar body weight on days 4, 8, 12 and 16 after birth, regardless of being mixed with piglets of higher weights or not; however, the survival rate until day 16 was most compromised in LG3 piglets compared to the other groups. Despite the lack of influence of littermates' weight on the growth of low BW piglets, their survival rate indicates that they should not be mixed with high BW piglets...

O objetivo do estudo foi avaliar o comportamento, a taxa de sobrevivência pré-desmame e o desempenho de crescimento de leitões leves ao nascer uniformizados com leitões de maior peso ao nascer (PN). Os leitões foram transferidos para 60 fêmeas e divididos em três grupos (G; n=20): G1 - 12 leitões de baixo PN (0,80-1,25kg); G2 - seis leitões de baixo PN e seis com PN intermediário (1,40-1,60kg); e G3 - seis leitões de baixo PN e seis leitões pesados (>1,70kg). Para a análise, os grupos G2 e G3 foram subdivididos em LG2 (seis G2 leitões leves); IG2 (seis G2 leitões de peso intermediário); LG3 (seis G3 leitões leves) e HG3 (seis G3 leitões pesados). Observações de comportamento foram realizadas nos dias 1, 2, 4 e 6 (observações visuais diretas) e nos dias 3 e 5 (gravações) após o nascimento. A porcentagem de mamadas perdidas foi maior no grupo LG3 quando comparado aos grupos LG1, IG2 e HG3, nos dias 1 e 2. No dia 4, leitões leves (LG1, LG2 e LG3) perderam maior número de mamadas do que os grupos IG2 e HG3. No dia 3, a gravação mostrou maior porcentagem de perda de mamadas nos grupos LG1, LG2 e LG3 do que no grupo HG3. No dia 1, o número de brigas durante a mamada foi maior nos grupos IG2 do que nos grupos LG1 e LG3. Também no dia 1, o número de brigas e porcentagem de leitões envolvidos em brigas, durante 15 minutos após a mamada, foi maior nos grupos LG1, LG3 e HG3 do que no grupo LG2. Brincadeiras foram mais observadas no dia 2 nos grupos IG2 e HG3 quando comparado aos grupos LG1, LG2 e LG3. Leitões leves (LG1, LG2 e LG3) apresentaram peso semelhante nos dias 4, 8, 12 e 16 após o nascimento, independentemente de serem misturados ou não com leitões pesados. No entanto, a taxa de sobrevivência até o dia 16 foi mais comprometida nos leitões do grupo LG3 do que nos outros grupos. Apesar da falta de influência do peso das leitegadas no crescimento de leitões de baixo PN, a taxa de sobrevivência indicou que estes não devem ser misturados com leitões de maior PN...

Artificial insemination of gilts with 1.5 billion sperms stored in different periods associated with different pre-ovulatory intervals.

This study evaluated the reproductive performance of gilts inseminated at three intervals before ovulation (0-12, 13-23, 24-30 h) with sperm doses (SD) stored for 0-48 and 96-120 h. A total of 218 PIC Camborough 22 gilts were inseminated once with SD of 1.5 x 10(9) sperms. Pregnant gilts (n = 166) were slaughtered 30.8 +/- 3.7 days after artificial insemination. The number of corpora lutea (CL) and total embryos (TE) was counted. Pregnancy rates (PR) were analysed by chi-square test. TE and embryonic survival (ES), obtained as the ratio between viable embryos and CL, were analysed by GLM procedure (SAS) and mean values were compared by Tukey's test. Pregnancy rate was similar among artificial insemination-ovulation (AIOV) intervals when semen was stored for 0-48 h. However, the lowest PR was observed in the 24-30 h AIOV interval with storage time (ST) of 96-120 h (p < 0.05). There was a significant effect of the interaction between ST and AIOV (p < 0.05) on TE and ES variables. Total embryos and ES did not differ (p > 0.05) among AIOV intervals in ST of 0-48 h. However, gilts inseminated at 24-30 h AIOV interval with ST of 96-120 h showed a reduction of 6.7 embryos (p < 0.05) compared with gilts in the same interval inseminated with semen stored for 0-48 h. ES for the 24-30 h AIOV interval and ST of 96-120 h was lower than that observed in the other groups (p < 0.05).

[Studies regarding a new contrast medium for demonstrating the patency of bile ducts (author's transl)]. / Untersuchungen über ein neues Kontrastmittel zur Darstellung der ableitenden Gallenwege

The contrast medium Endomirabil was tested in 103 patients. It produced few side-effects when 20 ml was injected pro examination over a 5 minute period. The rate of visable heterotopic contrast medium elimination is very low. The optimal time for making an x-ray to demonstrate bile ducts and gall bladder is 60-90 minutes after the injection. As a result, the number of x-ray films pro examination can be reduced. The unusually long filling of the bile ducts makes it possible to use tomography up to 90 minutes after the injection. This should be advantageous for radiological departments with limited capacity for tomography. Parenchymal damages induced by contrast medium could not be reduced from the chemical analyses.

Successful induction of follicular maturation and ovulation by prolonged treatment with LH-releasing hormone in women with anorexia nervosa.

Four women with anorexia nervosa were treated with synthetic LH-releasing hormone (LRH) in an attempt to induce ovulation. All the women had very low pretreatment levels of gonadotropins and estrogens. Administration of LRH resulted in significant gonadotropin increases. The FSH response to LRH in relation to the LH response was higher than in regularly menstruating women. LRH (500 mug) was administered parenterally three times daily over about 4 weeks. During this period there were no significant effects on mood, eating behavior, weight, or libido. All the women responded with follicular maturation and ovulation to the prolonged LRH treatment.

Self-inflicted haematuria and the syndrome of hospital addiction.

Self-inflicted haematuria may occur as part of the so-called Münchhausen syndrome or, better, the syndrome of hospital addiction. This rare but important differential diagnosis must be kept in mind in the investigation of obscure urological cases with long-standing and polysymptomatic histories. Two patients with factitious haematuria and hospital addiction are described. Some practical viewpoints on aetiology, diagnosis and management are given. An early recognition of the syndrome is important in order to avoid unnecessary and expensive investigations.

Epidemiology of secondary amenorrhea. I. Incidence and prevalence rates.

PIP: The study was designed to investigate the epidemiology of secondary amenorrhea within a county of Sweden. By means of questionnaire data regarding the occurrence of secondary amenorrhea of more than 3 months duration were collected together with background variables such as age, marital status, pregnancy history, use of oral contraceptives, and smoking habits. Subjects consisted of 2000 women of a total population of 30,000 women of age group 18-45 years in Uppsala county. From a computer list of all women born on day 10 or 20 of every month a 1 in 15 sample of the female population in the age group 18 to 45 years was obtained. Eventually 93.1% answered the questionnaire. Women who reported amenorrhea of more than 3 months duration in the past year were sent a second questionnaire asking for information regarding social and medical circumstances considered to be of interest. 258 women (13.8%) of the 1862 gave a history of amenorrhea of more than 3 months duration during the past year. The amenorrhea was due to pregnancy in 183 women (9.8%), secondary to surgical treatment in 13 women (.7%). 62 women, 3.3% were considered to have secondary amenorrhea. No case of primary amenorrhea was found. The age at menarche made no significant difference. 65% of the total group had borne a child. 23% were using oral contraceptives, 1/3 of the youngest and 1/10 of the oldest. 1/2 of the women under age 35 were cigarette smokers as compared to 1/3 of those above age 35. Of the factors considered; age, marital status, residence (city or rural), smoking habits and pregnancy history, only the age factor was found to be significant (t = 2.07; p less than .05). A marked covariation between the use of oral contraceptives and smoking habits was found. A plausible causal relationship between previous use of oral contraceptives and the occurrence of secondary amenorrhea was found in about 16% of the women with amenorrhea. However, findings indicate that the true incidence of secondary amenorrhea due to previous use of oral contraceptive agents is very low, .7% in the present study.^ieng

Epidemiology of secondary amenorrhea. II. A retrospective evaluation of etiology with special regard to psychogenic factors and weight loss.

PIP: A random sample of 41 women aged 18 to 35 years with secondary amenorrhea within Uppsala County, Sweden, were compared to 82 age-matched nonamenorrheic women with respect to a number of background variables of etiological interest, especially psychogenic factors and weight loss. Social-hygiene factors and gynecologic data were also considered. The study was retrospective and performed by a postal inquiry. In the amenorrheic group significant differences were obtained (p less than .05) for the following items: a higher proportion of unmarried women and women with intellectual occupations; a higher proportion with a greater incidence of stressful life events; more consumption of sedatives or hypnotic drugs; and more underweight. Previous menstrual irregularity was also more common. Amenorrhea following use of oral contraceptive agents was reported by 9 women, most of whom also showed pronounced underweight. Symptoms characteristic of anorexia were present in 2 amenorrheic women. There may have been others among those reporting marked underweight. The estimated prevalence of anorexia nervosa is 1 per 1000. The findings may be interpreted as either a true increase in incidence of the disorder or perhaps the method of investigation.^ieng

Characterization of epitopes on the 25 kD protein of the macrogametes/zygotes of Plasmodium falciparum.

A sexual stage-specific protein of Plasmodium falciparum with a Mr of 25,000 is one of the target antigens of transmission-blocking antibodies. The contributions of tertiary structure and post-translational modifications (glycosylation and acylation) to the structure of the epitopes on this protein were the subject of detailed investigations. After modification of the three-dimensional structure and modification or cleavage of carbohydrate groups and linked fatty acids, the immunological reactivity was investigated by three different techniques: (i) immunoprecipitation of radiolabelled proteins, (ii) enzyme-linked immunosorbent assay (ELISA), and (iii) Western blotting. The results of the experiments indicate that the immunological reactivity of the major epitopes on the 25 kD protein, including the epitope involved in transmission-blocking immunity, are dependent on the tertiary structure of the protein and on the presence of linked fatty acids, but not on the presence or absence of carbohydrate groups.

The effect of long-term inhibition of mitochondrial protein synthesis on the oxidation capacity of mitochondria for NADH-linked substrates.

Experiments are presented showing that specific inhibition of mitochondrial protein synthesis by tetracyclines decreases the activity of the NADH-dehydrogenase complex in liver mitochondria, if rats are treated for long periods with these antibiotics. The corresponding inhibition of this complex in tumor cells (Zajdela hepatoma) and tumor mitochondria (Leydig cell tumor) is even more pronounced. It is concluded that the mitochondrial genetic system is involved in the assembly of the NADH-dehydrogenase complex, most likely by coding for one or more subunits. It is argued that this information, contrary to the situation for cytochrome c oxidase, the cytochrome bc1 complex and ATPsynthase, has been missed in previous experiments employing differential inhibition of mitochondrial protein synthesis, because of the circumstance that the inhibition did not reach the level at which it became rate-limiting.