ABSTRACT
AIM: We aimed to study sex differences in long-term survival following out-of-hospital cardiac arrest (OHCA) compared to the general population, and determined associations for comorbidities, social characteristics, and resuscitation characteristics with survival in women and men separately. METHODS: We followed 2,452 Danish (530 women and 1,922 men) and 1,255 Dutch (259 women and 996 men) individuals aged ≥25 years, who survived 30 days post-OHCA in 2009-2015, until 2019. Using Poisson regression analyses we assessed sex differences in long-term survival and sex-specific associations of characteristics mutually adjusted, and compared survival with an age- and sex-matched general population. The potential predictive value was assessed with the Concordance-index. RESULTS: Post-OHCA survival was longer in women than men (adjusted incidence rate ratio (IRR) for mortality 0.74, 95%CI 0.61-0.89 in Denmark; 0.86, 95%CI 0.65-1.15 in the Netherlands). Both sexes had a shorter survival than the general population (e.g., IRR for mortality 3.07, 95%CI 2.55-3.70 and IRR 2.15, 95%CI 1.95-2.37 in Danish women and men). Higher age, glucose lowering medication, no dyslipidaemia medication, unemployment, and a non-shockable initial rhythm were associated with shorter survival in both sexes. Cardiovascular medication, depression/anxiety medication, living alone, low household income, and residential OHCA location were associated with shorter survival in men. Not living with children and bystander cardiopulmonary resuscitation provision were associated with shorter survival in women. The Concordance-indexes ranged from 0.51 to 0.63. CONCLUSIONS: Women survived longer than men post-OHCA. Several characteristics were associated with long-term post-OHCA survival, with some sex-specific characteristics. In both sexes, these characteristics had low predictive potential.
Subject(s)
Cardiopulmonary Resuscitation , Comorbidity , Out-of-Hospital Cardiac Arrest , Humans , Out-of-Hospital Cardiac Arrest/therapy , Out-of-Hospital Cardiac Arrest/mortality , Male , Female , Denmark/epidemiology , Middle Aged , Netherlands/epidemiology , Aged , Cardiopulmonary Resuscitation/statistics & numerical data , Cardiopulmonary Resuscitation/methods , Sex Factors , Adult , Registries , Survival Rate/trendsABSTRACT
AIM: Women have less favorable resuscitation characteristics than men. We investigated whether the Advanced Life Support Termination of Resuscitation rule (ALS-TOR) performs equally in women and men. Additionally, we studied whether adding or removing criteria from the ALS-TOR improved classification into survivors and non-survivors. METHODS: We analyzed 6,931 female and 14,548 male out-of-hospital cardiac arrest (OHCA) patients from Dutch and Swedish registries, and validated in 10,772 female and 21,808 male Danish OHCA patients. Performance measures were calculated for ALS-TOR in relation to 30-day survival. Recursive partitioning analysis was performed with the ALS-TOR criteria, as well as age, comorbidities, and additional resuscitation characteristics (e.g. initial rhythm, OHCA location). Finally, we explored if we could reduce the number of ALS-TOR criteria without loss of prognostic value. RESULTS: The ALS-TOR had a specificity and positive predictive value (PPV) of ≥99% in both women and men (e.g. PPV 99.9 in men). Classification by recursive partitioning analysis showed a high sensitivity but a PPV below 99%, thereby exceeding the acceptable miss rate of 1%. A combination of no return of spontaneous circulation (ROSC) before transport to the hospital and unwitnessed OHCA resulted in nearly equal specificity and PPV, higher sensitivity, and a lower transport rate to the hospital than the ALS-TOR. CONCLUSION: For both women and men, the ALS-TOR has high specificity and low miss rate for predicting 30-day OHCA survival. We could not improve the classification with additional characteristics. Employing a simplified version may decrease the number of futile transports to the hospital.
Subject(s)
Amyotrophic Lateral Sclerosis , Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Humans , Male , Female , Out-of-Hospital Cardiac Arrest/therapy , Resuscitation Orders , Cardiopulmonary Resuscitation/methods , Decision Support TechniquesABSTRACT
STUDY QUESTION: Are there more de novo mutations (DNMs) present in the genomes of children born through medical assisted reproduction (MAR) compared to spontaneously conceived children? SUMMARY ANSWER: In this pilot study, no statistically significant difference was observed in the number of DNMs observed in the genomes of MAR children versus spontaneously conceived children. WHAT IS KNOWN ALREADY: DNMs are known to play a major role in sporadic disorders with reduced fitness such as severe developmental disorders, including intellectual disability and epilepsy. Advanced paternal age is known to place offspring at increased disease risk, amongst others by increasing the number of DNMs in their genome. There are very few studies reporting on the effect of MAR on the number of DNMs in the offspring, especially when male infertility is known to be affecting the potential fathers. With delayed parenthood an ongoing epidemiological trend in the 21st century, there are more children born from fathers of advanced age and more children born through MAR every day. STUDY DESIGN, SIZE, DURATION: This observational pilot study was conducted from January 2015 to March 2019 in the tertiary care centre at Radboud University Medical Center. We included a total of 53 children and their respective parents, forming 49 trios (mother, father and child) and two quartets (mother, father and two siblings). One group of children was born after spontaneous conception (n = 18); a second group of children born after IVF (n = 17) and a third group of children born after ICSI combined with testicular sperm extraction (ICSI-TESE) (n = 18). In this pilot study, we also subdivided each group by paternal age, resulting in a subgroup of children born to younger fathers (<35 years of age at conception) and older fathers (>45 years of age at conception). PARTICIPANTS/MATERIALS, SETTING, METHODS: Whole-genome sequencing (WGS) was performed on all parent-offspring trios to identify DNMs. For 34 of 53 trios/quartets, WGS was performed twice to independently detect and validate the presence of DNMs. Quality of WGS-based DNM calling was independently assessed by targeted Sanger sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: No significant differences were observed in the number of DNMs per child for the different methods of conception, independent of parental age at conception (multi-factorial ANOVA, f(2) = 0.17, P-value = 0.85). As expected, a clear paternal age effect was observed after adjusting for method of conception and maternal age at conception (multiple regression model, t = 5.636, P-value = 8.97 × 10-7), with on average 71 DNMs in the genomes of children born to young fathers (<35 years of age) and an average of 94 DNMs in the genomes of children born to older fathers (>45 years of age). LIMITATIONS, REASONS FOR CAUTION: This is a pilot study and other small-scale studies have recently reported contrasting results. Larger unbiased studies are required to confirm or falsify these results. WIDER IMPLICATIONS OF THE FINDINGS: This pilot study did not show an effect for the method of conception on the number of DNMs per genome in offspring. Given the role that DNMs play in disease risk, this negative result is good news for IVF and ICSI-TESE born children, if replicated in a larger cohort. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Netherlands Organisation for Scientific Research (918-15-667) and by an Investigator Award in Science from the Wellcome Trust (209451). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.
Subject(s)
Fertilization in Vitro , Sperm Injections, Intracytoplasmic , Adult , Child , Female , Fertilization , Humans , Male , Mutation , Pilot Projects , Sperm Injections, Intracytoplasmic/methodsABSTRACT
De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10-5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10-4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.
Subject(s)
Azoospermia/genetics , Cell Cycle Proteins/genetics , DNA-Binding Proteins/genetics , Genetic Predisposition to Disease , Loss of Function Mutation , Mutation, Missense , Oligospermia/genetics , RNA-Binding Proteins/genetics , Tumor Suppressor Proteins/genetics , Adult , Azoospermia/pathology , Case-Control Studies , Cell Cycle Proteins/deficiency , DNA-Binding Proteins/deficiency , Exome , Gene Expression , Gene Expression Profiling , Humans , Male , Oligospermia/pathology , Tumor Suppressor Proteins/deficiency , Exome SequencingABSTRACT
BACKGROUND: There is no consensus whether patients with healthcare-associated pneumonia (HCAP) should be considered as a patient with hospital-acquired pneumonia (HAP) and treated with broad-spectrum antibiotics, or as a patient with community-acquired pneumonia (CAP), and treated with narrow-spectrum antibiotics. HCAP research has focused mostly on the predictive value for non-susceptibility to broad-spectrum antibiotics and multi-drug resistant pathogens, in settings with moderate to high levels of antibiotic resistance. We investigated whether HCAP criteria predicts non-susceptibility to different empirical strategies, including narrow-spectrum antibiotics in the Dutch setting. METHODS: In a post hoc analysis of patients with moderate-severe CAP in seven Dutch hospitals, we compared in vitro antibiotic susceptibilities of definite and possible causative pathogens of CAP and HCAP to amoxicillin and broader antibiotic regimens. In a sensitivity analysis, pathogens with missing susceptibilities were assumed susceptible (best-case scenario) or non-susceptible (worst-case scenario). RESULTS: Among 2,283 patients with moderate-severe CAP, 23.1% (n = 527) were classified as HCAP. Non-susceptibility to amoxicillin ranged from 11.3% (95% CI 9.9-12.8%; best-case) to 14.4% (95% CI 12.8-16.1%; worst-case) in CAP patients and from 16.7% (95% CI 13.8-20.1%; best-case) to 19.7% (95% CI 16.6-23.3%; worst-case) in HCAP patients. The largest reduction in non-susceptibility was achieved by adding ciprofloxacin to amoxicillin treatment in both CAP patients (10% absolute risk reduction) and HCAP patients (11-16% reduction). CONCLUSIONS: In the Netherlands, HCAP criteria predict higher amoxicillin non-susceptibility in patients hospitalized with moderate-severe CAP. Although broadening the antibiotic spectrum of empiric treatment reduced the likelihood of non-susceptibility, absolute reductions of non-susceptibility in HCAP patients were too low to justify the universal use of broad-spectrum empirical therapy.No abstract available.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/drug therapy , Healthcare-Associated Pneumonia/drug therapy , Microbial Sensitivity Tests/statistics & numerical data , Pneumonia, Bacterial/drug therapy , Aged , Amoxicillin/therapeutic use , Community-Acquired Infections/microbiology , Drug Resistance, Bacterial , Female , Healthcare-Associated Pneumonia/microbiology , Humans , Male , Middle Aged , Netherlands , Pneumonia, Bacterial/microbiologyABSTRACT
Resection margins are frequently studied in patients with oral squamous cell carcinoma and are accepted as a constant prognostic factor. While most evidence is based on soft tissue margins, reported data for bone resection margins are scarce. The aim of this retrospective study was to evaluate and determine the utility of surgical margins in bone resections for oral cavity squamous cell carcinoma (OCSCC). The status of bone resection margins and their impact on survival was investigated in patients who had undergone segmental mandibulectomy for OCSCC. Medical records were retrieved for the years 2000-2012; 127 patients were identified and included in the study. Tumour-positive bone resection margins were found in 21% of the patients. The 5-year overall survival was significantly lower in this group (P<0.005). Therefore, there is a need for intraoperative feedback on the status of bone resection margins to enable immediate additional resection where necessary. Although the lack of intraoperative methods for the evaluation of bone tissue has been addressed by many authors, there is still no reliable method for widespread use. Future research should focus on an objective, accurate, and rapid method of intraoperative assessment for the entire bone resection margin to optimize patient outcomes.
Subject(s)
Carcinoma, Squamous Cell/surgery , Mandibular Neoplasms/surgery , Mandibular Osteotomy , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Female , Humans , Male , Mandibular Neoplasms/diagnostic imaging , Mandibular Neoplasms/pathology , Margins of Excision , Middle Aged , Neoplasm Staging , Retrospective Studies , Treatment OutcomeABSTRACT
Hypercortisolism is associated with mood disorders such as depression and bipolar disorder. A 75-year-old female patient who had been diagnosed with bipolar disorder forty years ago was admitted to our hospital with a severe, therapy-resistant mania. Careful diagnostic considerations, resulted in the patient being diagnosed with Cushing's syndrome. Treatment with metyrapone led to a swift improvement of the patient's symptoms. Could Cushing's syndrome underlie this patient's psychiatric history? Or are two co-existing, intertwining causes responsible for the psychiatric symptoms? The case illustrates that even if a patient has a long history of psychiatric problems that have been plausibly diagnosed over time, clinicians and psychiatrists should always consider the possibility that there may be an underlying somatic cause for the patient's psychiatric symptoms.
Subject(s)
Bipolar Disorder/epidemiology , Cushing Syndrome/epidemiology , Aged , Bipolar Disorder/etiology , Cushing Syndrome/complications , Diagnosis, Differential , Female , Humans , Metyrapone/therapeutic useABSTRACT
The paucity of observed supermassive black hole binaries (SMBHBs) may imply that the gravitational wave background (GWB) from this population is anisotropic, rendering existing analyses suboptimal. We present the first constraints on the angular distribution of a nanohertz stochastic GWB from circular, inspiral-driven SMBHBs using the 2015 European Pulsar Timing Array data. Our analysis of the GWB in the ~2-90 nHz band shows consistency with isotropy, with the strain amplitude in l>0 spherical harmonic multipoles â²40% of the monopole value. We expect that these more general techniques will become standard tools to probe the angular distribution of source populations.
ABSTRACT
Tumor-positive resection margins are a major problem in oral cancer surgery. High-wavenumber Raman spectroscopy is a reliable technique to determine the water content of tissues, which may contribute to differentiate between tumor and healthy tissue. The aim of this study was to examine the use of Raman spectroscopy to differentiate tumor from surrounding healthy tissue in oral squamous cell carcinoma. From 14 patients undergoing tongue resection for squamous cell carcinoma, the water content was determined at 170 locations on freshly excised tongue specimens using the Raman bands of the OH-stretching vibrations (3350-3550 cm(-1)) and of the CH-stretching vibrations (2910-2965 cm(-1)). The results were correlated with histopathological assessment of hematoxylin and eosin stained thin tissue sections obtained from the Raman measurement locations. The water content values from squamous cell carcinoma measurements were significantly higher than from surrounding healthy tissue (p-value < 0.0001). Tumor tissue could be detected with a sensitivity of 99% and a specificity of 92% using a cutoff water content value of 69%. Because the Raman measurements are fast and can be carried out on freshly excised tissue without any tissue preparation, this finding signifies an important step toward the development of an intraoperative tool for tumor resection guidance with the aim of enabling oncological radical surgery and improvement of patient outcome.
Subject(s)
Carcinoma, Squamous Cell/chemistry , Health , Mouth Neoplasms/chemistry , Spectrum Analysis, Raman , Water/analysis , Carcinoma, Squamous Cell/pathology , Humans , Mouth Neoplasms/pathologyABSTRACT
A predictive modelling technique was employed to estimate wastewater temperatures in sewer pipes. The simplicity of abductive predictive models attracts large numbers of users due to their minimal computation time and limited number of measurable input parameters. Data measured from five sewer pipes over a period of 12 months provide 33,900 training entries and 39,000 evaluation entries to support the models' development. Two simple predictive models for urban upstream combined sewers and large downstream collector sewers were developed. They delivered good correlation between measured and predicted wastewater temperatures proven by their R(2) values of up to 0.98 and root mean square error (RMSE) of the temperature change along the sewer pipe ranging from 0.15 °C to 0.33 °C. Analysis of a number of potential input parameters indicated that upstream wastewater temperature and downstream in-sewer air temperature were the only input parameters that are needed in the developed models to deliver this level of accuracy.
Subject(s)
Models, Theoretical , Sewage/analysis , Temperature , Waste Disposal, Fluid , Wastewater/analysis , Belgium , CitiesABSTRACT
Modelling of wastewater temperatures along a sewer pipe using energy balance equations and assuming steady-state conditions was achieved. Modelling error was calculated, by comparing the predicted temperature drop to measured ones in three combined sewers, and was found to have an overall root mean squared error of 0.37 K. Downstream measured wastewater temperature was plotted against modelled values; their line gradients were found to be within the range of 0.9995-1.0012. The ultimate aim of the modelling is to assess the viability of recovering heat from sewer pipes. This is done by evaluating an appropriate location for a heat exchanger within a sewer network that can recover heat without impacting negatively on the downstream wastewater treatment plant (WWTP). Long sewers may prove to be more viable for heat recovery, as heat lost can be reclaimed before wastewater reaching the WWTP.
Subject(s)
Drainage, Sanitary , Hot Temperature , Wastewater , Conservation of Natural Resources , Models, Theoretical , Sewage , Time Factors , Waste Disposal, FluidABSTRACT
Spin selectivity in a ferromagnet results from a difference in the density of up- and down-spin electrons at the Fermi energy as a consequence of which the scattering rates depend on the spin orientation of the electrons. This property is utilized in spintronics to control the flow of electrons by ferromagnets in a ferromagnet (F1)/normal metal (N)/ferromagnet (F2) spin valve, where F1 acts as the polarizer and F2 the analyser. The feasibility of superconducting spintronics depends on the spin sensitivity of ferromagnets to the spin of the equal spin-triplet Cooper pairs, which arise in superconductor (S)-ferromagnet (F) heterostructures with magnetic inhomogeneity at the S-F interface. Here we report a critical temperature dependence on magnetic configuration in current-in-plane F-S-F spin valves with a holmium spin mixer at the S-F interface providing evidence of a spin selectivity of the ferromagnets to the spin of the triplet Cooper pairs.
ABSTRACT
Apc-driven tumor formation in patients and Apc-mutant mouse models is generally attributed to increased levels of ß-catenin signaling. We and others have proposed that a specific level of ß-catenin signaling is required to successfully initiate tumor formation, and that each tissue prefers different dosages of signaling. This is illustrated by APC genotype-tumor phenotype correlations in cancer patients, and by the different tumor phenotypes displayed by different Apc-mutant mouse models. Apc1638N mice, associated with intermediate ß-catenin signaling, characteristically develop intestinal tumors (<10) and extra-intestinal tumors, including cysts and desmoids. Apc1572T mice associated with lower levels of ß-catenin signaling are free of intestinal tumors, but instead develop mammary tumors. Although the concept of ß-catenin signaling dosage and its impact on tumor growth among tissues is gaining acceptance, it has not been formally proven. Additionally, alternative explanations for Apc-driven tumor formation have been proposed. To obtain direct evidence for the dominant role of ß-catenin dosage in tumor formation and tissue-specific tumor predisposition, we crossed Apc1638N mice with heterozygous ß-catenin knockout mice, thereby reducing ß-catenin levels. Whereas all the Apc1638N;Ctnnb1(+/+) mice developed gastrointestinal tumors, none were present in the Apc1638N;Ctnnb1(-/+) mice. Incidence of other Apc1638N-associated lesions, including desmoids and cysts, was strongly reduced as well. Interestingly, Apc1638N;Ctnnb1(-/+) females showed an increased incidence of mammary tumors, which are normally rarely observed in Apc1638N mice, and the histological composition of the tumors resembled that of Apc1572T-related tumors. Hereby, we provide in vivo genetic evidence confirming the dominant role of ß-catenin dosage in tumor formation and in dictating tumor predisposition among tissues in Apc-driven cancer.
Subject(s)
Genes, APC , Neoplasms/genetics , Neoplasms/metabolism , Signal Transduction , beta Catenin/metabolism , Animals , Disease Models, Animal , Female , Genetic Predisposition to Disease , Genotype , Humans , Male , Mice , Mice, Knockout , Mice, Transgenic , Neoplasms/pathology , beta Catenin/geneticsABSTRACT
Gilt progeny have lighter weaning weights and greater postweaning medication and mortality rates compared with the progeny of older parity sows. Because weaning weight has been positively correlated with postweaning survival, this study aimed to determine whether the provision of supplemental milk preweaning could improve weaning weight and subsequent weights as well as postweaning survival of gilt progeny. The study was replicated in summer and winter as the effects of supplemental milk were expected to vary with season. The progeny of 80 gilts (parity 0) and 80 sows (parity 2 to 5) were allocated to both treatments: with or without supplemental milk in these 2 seasons with 5 sheds/season. Litter size was standardized (10 to 11 piglets) and each piglet was weighed at birth, d 21, weaning (4 wk), and 10 wk of age. Medications and mortalities were recorded both preweaning and postweaning. Pigs were housed within treatment groups postweaning, and ADFI and G:F were measured. Gilt progeny were 200 g lighter at birth in both replicates (P < 0.001) and were 500 g lighter at weaning in the winter replicate (P < 0.05) compared with sow progeny. The provision of supplemental milk improved weaning weight for both gilt and sow progeny by 800 g in summer (P < 0.05) and by 350 g in winter (P < 0.05). This improvement in weaning weight had no effect on the incidence of death or disease in milk-supplemented progeny of either gilts or sows (P > 0.05). Supplemental milk disappearance (the daily difference between the volume of milk provided and the residue left in the drinker) was greater in summer than winter (by 130 mL/piglet d(-1); P < 0.05) as were the associated weaning weight benefits. The weaning weights of supplemented gilt progeny reached or exceeded that of nonsupplemented sow progeny. Gilt progeny had greater postweaning mortality (2.6%) and medication rates (6.2%) than sow progeny (1 and 2.2%, respectively; both P < 0.05) in both seasons, but medication rates were greater in winter (7.2%) for both treatment groups than in summer (1.9%; P < 0.05). Gilt progeny also had less postweaning ADFI than sow progeny in winter (528 and 636 g, respectively; P < 0.05) with no dam parity effect on G:F (both P > 0.05). The hypothesis that supplemental milk provision did increase gilt progeny weaning weight was supported (especially in summer) but the supplementation had no effect on postweaning weights and survival. Efforts to improve gilt progeny postweaning growth and survival need to be aimed at improving health and immunity, not just weaning weight.
Subject(s)
Body Weight , Dietary Supplements/analysis , Milk/metabolism , Sus scrofa/growth & development , Weaning , Animals , Female , Male , Parity , Pregnancy , Seasons , Sus scrofa/physiology , Weight GainABSTRACT
In the past years we developed high-resolution screening platforms involving separation of bioactive mixtures and on-line or at-line bioassays for a wide variety of biological targets with parallel mass spectrometric detection and identification. In the current research, we make a major step forward in the development of at-line bioassays by implementation of radioligand receptor binding and functional cellular assays to evaluate bioactvity and selectivity. We demonstrate a new platform for high-resolution metabolic profiling of lead compounds for functional activity and selectivity toward the human histamine H(4) receptor (hH(4)R), a member of the large family of membrane-bound G protein-coupled receptors. In this platform analytical chemistry, cell biology and pharmacology are merged. The methodology is based on chromatographic separation of metabolic mixtures by HPLC coupled to high-resolution fractionation onto (multiple) microtiter well plates for complementary assaying. The methodology was used for efficient and rapid metabolic profiling of the drug clozapine and three selective hH(4)R lead compounds. With this new platform metabolites with undesired alterations in target selectivity profiles can be readily identified. Moreover, the parallel identification of metabolite structures, with accurate-mass measurements and MS/MS, allowed identification of liable metabolic 'hotspots' for further lead optimization and plays a central role in the workflow and in this study. The methodology can be easily adapted for use with other receptor screening formats. The efficient combination of pharmacological assays with analytical techniques by leveraging high-resolution at-line fractionation as a linking technology will allow implementation of comprehensive metabolic profiling in an early phase of the drug discovery process.
Subject(s)
Drug Discovery/methods , Receptors, G-Protein-Coupled/metabolism , Receptors, Histamine/metabolism , Tandem Mass Spectrometry/methods , Cell Line, Tumor , Cell Membrane/metabolism , Chromatography, Liquid , Clozapine/chemistry , Clozapine/metabolism , HEK293 Cells , Histamine , Humans , Ligands , Piperazines/chemistry , Piperazines/metabolism , Quinazolinones/chemistry , Quinazolinones/metabolism , Radioligand Assay , Receptors, G-Protein-Coupled/chemistry , Receptors, Histamine/chemistry , Receptors, Histamine H4ABSTRACT
BACKGROUND: Voice disorders have a multifactorial genesis and may be present in various ways. They can cause a significant communication handicap and impaired quality of life. OBJECTIVE: To assess the effect of vocal fold lesions and voice quality on voice handicap and psychosomatic well-being. METHODS: Female patients, aged 18-65 years, who were referred to the outpatient clinic with voice problems were subsequently assessed. Laryngostroboscopic examination and acoustic voice analysis were carried out, and the patients were asked to fill in the Voice Handicap Index (VHI) and Symptom Check List-90 questionnaires. RESULTS: Eighty-two patients were included. In 43 patients (52.4%), a vocal fold lesion was observed. The VHI and psychosomatic well-being did not differ significantly between patients with and without a vocal fold lesion. The patients with a vocal fold lesion showed lower scores on the Dysphonia Severity Index (DSI) compared with those without a vocal fold lesion. However, the DSI was not correlated with voice handicap and psychosomatic well-being, except for the VHI physical subscale. CONCLUSION: Objective measurement does not necessarily correlate with the subjective appraisal of the patient's voice handicap and psychosomatic well-being. Furthermore, the criterion of the presence of a vocal fold lesion as the base of indemnity that is applied by health insurance institutions should be questioned.
Subject(s)
Vocal Cords/pathology , Voice Disorders/pathology , Voice Disorders/psychology , Voice Quality , Adolescent , Adult , Aged , Female , Humans , Middle Aged , Prospective Studies , Psychophysiologic Disorders/pathology , Young AdultABSTRACT
Birth weight positively predicts postnatal growth and performance in pigs and can be increased by sustained maternal porcine ST (pST) treatment from d 25 to 100 of pregnancy (term â¼115 d). The objective of this study was to test whether a shorter period of maternal pST treatment in late pregnancy (d 75 to 100) could also increase birth and weaning weights of progeny under commercial conditions. Gilts (parity 0) and sows (parities 2 and 3) were not injected (controls) or injected daily with pST (gilts: 2.5 mgâ¢d(-1), sows: 4.0 mgâ¢d(-1), both â¼13 to 14 µgâ¢kg(-1)â¢d(-1)) from d 75 to 100 of pregnancy. Litter size and BW were recorded at birth and weaning, and dams were followed through the subsequent mating and pregnancy. Maternal pST injections from d 75 to 100 increased litter average progeny weight at birth (+96 g, P = 0.034) and weaning (+430 g, P = 0.038) in sows, but had no effect on progeny weight in gilts (each P > 0.5). Maternal pST treatment did not affect numbers of live-born piglets and increased numbers of stillborn piglets in sows only (+0.4 pigs/litter, P = 0.034). Maternal pST treatment did not affect subsequent reproduction of dams. Together with our previous data, these results suggest that sustained increases in maternal pST are required to increase fetal and postnatal growth in gilt progeny, but that increasing maternal pST in late pregnancy may only be an effective strategy to increase fetal and possibly postnatal growth in sow progeny.
Subject(s)
Animals, Newborn , Body Weight/drug effects , Growth Hormone/pharmacology , Swine/growth & development , Weaning , Adipose Tissue/physiology , Animals , Eating , Female , Growth Hormone/administration & dosage , Lactation , Parity , PregnancyABSTRACT
Supplementing diets with n-3 fatty acids from fish oil has been shown to improve reproductive performance in dairy cattle and sheep, but there is little published literature on its effects in sows. The aim of this study was to evaluate the reproductive performance of sows fed fish oil as a source of n-3 PUFA prefarrowing and during lactation. From d 107.7 ± 0.1 of pregnancy, 328 sows ranging in parity from 0 to 7 (parity 1.95 ± 0.09, mean ± SE) were fed either a diet containing tallow (control) or an isocaloric diet containing 3 g of fish oil/kg of diet (n-3). Diets were formulated to contain the same amount of DE (13.9 MJ/kg), crude fat (54 g/kg), and CP (174 g/kg). Sows were fed their treatment diet at 3 kg daily for 8 d before farrowing and continued on treatment diets ad libitum until weaning at 18.7 ± 0.1 d of lactation. After weaning, all sows were fed a gestation diet without fish oil until their subsequent farrowing. There was no effect (P > 0.310) of feeding n-3 diets prefarrowing on piglet birth weight, preweaning growth rate, piglet weaning weight, or sow feed intake. However, n-3 sows had a larger subsequent litter size (10.7 ± 0.3 vs. 9.7 ± 0.3 total born; 10.2 ± 0.3 vs. 9.3 ± 0.3 born live; P < 0.05). In conclusion, this is the first study to demonstrate that feeding sows a diet containing n-3 PUFA from fish oil fed before farrowing and during lactation increased litter size in the subsequent parity independent of energy intake.
Subject(s)
Fatty Acids, Omega-3/pharmacology , Fish Oils/pharmacology , Litter Size/drug effects , Animal Feed/analysis , Animal Husbandry/methods , Animals , Animals, Newborn/growth & development , Diet/veterinary , Fatty Acids, Omega-3/analysis , Female , Lactation , Nutritive Value , Parity , Pregnancy , Swine/growth & development , Swine/physiologyABSTRACT
Piglet neonatal survival and postnatal growth and efficiency are positively related to birth weight. In gilts, daily maternal porcine ST (pST) injections from d 25 to 100 (term approximately 115 d), but not d 25 to 50, of pregnancy increase progeny birth weight. Daily maternal pST injections from d 25 to 50 increase fetal weight at d 50 in gilts and sows. We therefore hypothesized that daily pST injections from d 25 to 100, but not d 25 to 50, of pregnancy would increase birth weight similarly in both parities. Landrace x Large White gilts and sows were uninjected (controls) or were injected daily with pST (gilts: 2.5 mg/d; sows: 4.0 mg/d, each approximately 15 microg of pST/kg per day) from d 25 to 50 or 100 of pregnancy. Litter size and BW were recorded at birth, midlactation, and weaning. Dams were followed through the subsequent mating and pregnancy. Maternal pST injections from d 25 to 100, but not d 25 to 50, increased mean piglet birth weight by 11.6% in sows (P