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Scientific Reports May 2024Parkinson's disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group...
Parkinson's disease is a progressive neurodegenerative disorder in which loss of dopaminergic neurons in the substantia nigra results in a clinically heterogeneous group with variable motor and non-motor symptoms with a degree of misdiagnosis. Only 3-25% of sporadic Parkinson's patients present with genetic abnormalities that could represent a risk factor, thus environmental, metabolic, and other unknown causes contribute to the pathogenesis of Parkinson's disease, which highlights the critical need for biomarkers. In the present study, we prospectively collected and analyzed plasma samples from 194 Parkinson's disease patients and 197 age-matched non-diseased controls. N-acetyl putrescine (NAP) in combination with sense of smell (B-SIT), depression/anxiety (HADS), and acting out dreams (RBD1Q) clinical measurements demonstrated combined diagnostic utility. NAP was increased by 28% in Parkinsons disease patients and exhibited an AUC of 0.72 as well as an OR of 4.79. The clinical and NAP panel demonstrated an area under the curve, AUC = 0.9 and an OR of 20.4. The assessed diagnostic panel demonstrates combinatorial utility in diagnosing Parkinson's disease, allowing for an integrated interpretation of disease pathophysiology and highlighting the use of multi-tiered panels in neurological disease diagnosis.
Topics: Humans; Parkinson Disease; Male; Biomarkers; Female; Aged; Middle Aged; Putrescine; Prospective Studies; Case-Control Studies
PubMed: 38693432
DOI: 10.1038/s41598-024-60872-3 -
The Journal of Allergy and Clinical... Apr 2024Benralizumab and mepolizumab are interleukin (IL)-5Rα/interleukin-5-targeted monoclonal antibodies indicated as add-on treatments for patients with uncontrolled severe...
BACKGROUND
Benralizumab and mepolizumab are interleukin (IL)-5Rα/interleukin-5-targeted monoclonal antibodies indicated as add-on treatments for patients with uncontrolled severe eosinophilic asthma (SEA).
OBJECTIVE
To evaluate and compare the safety of benralizumab and mepolizumab among patients with SEA treated in MELTEMI and COLUMBA open-label, long-term extension studies, respectively.
METHODS
MELTEMI was an extension study of benralizumab every 4 weeks (q4w) or every 8 weeks (q8w) for adults (aged 18-75 y) with SEA. MELTEMI participants transitioned from the BORA extension, preceded by participation in 1 of 3 placebo-controlled studies (SIROCCO, CALIMA, or ZONDA). COLUMBA was an extension study of mepolizumab for patients (aged ≥ 12 y) with SEA who transitioned from the dose-ranging DREAM study. Safety endpoints were presented as drug exposure patient-years (MELTEMI, q4w 784.28, q8w 797.03; COLUMBA 1,201) for nonserious adverse events, serious adverse events, and infections; malignancies were counted numerically.
RESULTS
This analysis included 446 MELTEMI patients (benralizumab q4w 220; benralizumab q8w 226) and 347 COLUMBA patients (mepolizumab q4w). Viral upper respiratory tract infection was the most common nonserious adverse event in both studies (MELTEMI q8w 46.5%; q4w 47.3%; COLUMBA, 48.7%). Asthma-related events were the most common serious adverse events in both studies: MELTEMI 8.0% (q8w) and 8.6% (q4w) and COLUMBA 9.5%. Serious infections included pneumonia (MELTEMI q8w, 2 [0.9%]; COLUMBA, 6 [1.7%]); cellulitis (MELTEMI q8w, 1 [0.4%]; COLUMBA, 2 [0.6%]); and respiratory tract infections (COLUMBA, 2 [0.6%]). COLUMBA reported 6 malignancies and MELTEMI reported 4 malignancies in each group.
CONCLUSIONS
This analysis demonstrated generally similar safety events between mepolizumab and benralizumab in patients with SEA.
PubMed: 38677588
DOI: 10.1016/j.jaip.2024.04.033 -
Scientific Reports Apr 2024Suicide is prevalent among young adults, and epidemiological studies indicate that insomnia, nightmares, and depression are significantly associated with a high...
Suicide is prevalent among young adults, and epidemiological studies indicate that insomnia, nightmares, and depression are significantly associated with a high incidence of suicidal ideation (SI). However, the causal relationship between these factors and SI remains unclear. Therefore, the purpose of this study was to examine the association between nightmares and depression and insomnia and SI in young adults, as well as to develop a mediation model to investigate the causal relationship between insomnia, nightmare, depression, and SI. We assessed insomnia, nightmares, depression, and SI in 546 young adults using the Insomnia Severity Scale (ISI), Disturbing Dream and Nightmare Severity Scale (DDNSI), Depression Study Scale (CESD-20), and Columbia-Suicide Severity Rating Scale (C-SSRS). Using the Bootstrap method, the mediation effects of nightmares and depression between insomnia and SI were calculated. The results demonstrated that nightmares and depression fully mediated the relationship between insomnia and SI, including the chain-mediation of insomnia and SI between nightmare and depression with an effect value of 0.02, 95% CI 0.01-0.04, and depression as a mediator between insomnia and SI with an effect value of 0.22, 95% CI 0.15-0.29. This study found that depression and nightmares may be risk and predictive factors between insomnia and SI, which implies that the assessment and treatment of depression and the simple or linked effect of nightmares play crucial roles in preventing SI in young adults.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Suicidal Ideation; Dreams; Male; Female; Depression; Young Adult; Adult; Adolescent; Risk Factors
PubMed: 38670978
DOI: 10.1038/s41598-024-58774-5 -
Radiotherapy and Oncology : Journal of... Jul 2024Radiotherapy developed empirically through experience balancing tumour control and normal tissue toxicities. Early simple mathematical models formalized this practical... (Review)
Review
Radiotherapy developed empirically through experience balancing tumour control and normal tissue toxicities. Early simple mathematical models formalized this practical knowledge and enabled effective cancer treatment to date. Remarkable advances in technology, computing, and experimental biology now create opportunities to incorporate this knowledge into enhanced computational models. The ESTRO DREAM (Dose Response, Experiment, Analysis, Modelling) workshop brought together experts across disciplines to pursue the vision of personalized radiotherapy for optimal outcomes through advanced modelling. The ultimate vision is leveraging quantitative models dynamically during therapy to ultimately achieve truly adaptive and biologically guided radiotherapy at the population as well as individual patient-based levels. This requires the generation of models that inform response-based adaptations, individually optimized delivery and enable biological monitoring to provide decision support to clinicians. The goal is expanding to models that can drive the realization of personalized therapy for optimal outcomes. This position paper provides their propositions that describe how innovations in biology, physics, mathematics, and data science including AI could inform models and improve predictions. It consolidates the DREAM team's consensus on scientific priorities and organizational requirements. Scientifically, it stresses the need for rigorous, multifaceted model development, comprehensive validation and clinical applicability and significance. Organizationally, it reinforces the prerequisites of interdisciplinary research and collaboration between physicians, medical physicists, radiobiologists, and computational scientists throughout model development. Solely by a shared understanding of clinical needs, biological mechanisms, and computational methods, more informed models can be created. Future research environment and support must facilitate this integrative method of operation across multiple disciplines.
Topics: Humans; Radiobiology; Neoplasms; Precision Medicine
PubMed: 38670264
DOI: 10.1016/j.radonc.2024.110277 -
Behavioral Sciences (Basel, Switzerland) Apr 2024Spontaneous, unwilled subjective imagery and symbols (including dreams) often emerge in psychotherapy that can appear baffling and confound interpretation. Early...
Spontaneous, unwilled subjective imagery and symbols (including dreams) often emerge in psychotherapy that can appear baffling and confound interpretation. Early psychoanalytic theories seemed to diverge as often as they agreed on the meaning of such content. Nevertheless, after reviewing key findings in the empirical science of spontaneous thought as well as insights gleaned from neuroscience and especially embodied cognition, it is now possible to construct a more coherent theory of interpretation that is clinically useful. Given that thought is so thoroughly embodied, it is possible to demonstrate that universalities in human physiology yield universalities in thought. Such universalities can then be demonstrated to form a kind of biologically directed universal "code" for understanding spontaneous symbolic expressions that emerge in psychotherapy. An example is given that illustrates how this can be applied to clinical encounters.
PubMed: 38667115
DOI: 10.3390/bs14040319 -
Midwifery Jul 2024There has been an increase in the number of single women deciding to have children through the use of medically assisted reproduction (MAR). These women are referred to...
PROBLEM
There has been an increase in the number of single women deciding to have children through the use of medically assisted reproduction (MAR). These women are referred to as 'single mothers by choice' (SMC).
BACKGROUND
Previous studies have shown how SMC can feel stigmatised.
AIM
Explore if single women seeking fertility treatment in Denmark feel stigmatised.
METHODS
Six single women undergoing MAR at a public fertility clinic in Denmark were interviewed. The interviews were audiotaped, anonymised, and transcribed in full, after provided written consent by the participants to take part in the study. Data were analysed using qualitative content analysis.
FINDINGS
The women would have preferred to have a child in a relationship with a partner. Despite their dream of the nuclear family meaning a family group consisting of two parents and their children (one or more), the women choose to become SMC because motherhood was of such importance, and they feared they would otherwise become too old to have children. The participants did not experience stigma or negative responses to their decision, but they all had an awareness of the prejudices other people might have towards SMC.
CONCLUSION
This study contributes to the understanding of the experiences of single women seeking fertility treatment in a welfare state where there are no differences in the possibilities for different social classes to seek MAR.
Topics: Humans; Female; Denmark; Adult; Pilot Projects; Mothers; Qualitative Research; Choice Behavior; Fertility Clinics; Single Person; Single Parent; Reproductive Techniques, Assisted
PubMed: 38663056
DOI: 10.1016/j.midw.2024.104013 -
Critical Care (London, England) Apr 2024Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator...
Ventilator-associated pneumonia related to extended-spectrum beta-lactamase producing Enterobacterales during severe acute respiratory syndrome coronavirus 2 infection: risk factors and prognosis.
BACKGROUND
Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP.
PATIENTS AND METHODS
We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included.
RESULTS
We included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07-2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02-1.09], p = 0.002), PaO/FiO ratio on the day of VAP (OR 0.997 [0.994-0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15-12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP.
CONCLUSION
ESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.
Topics: Humans; Pneumonia, Ventilator-Associated; Escherichia coli; Cohort Studies; Prospective Studies; Critical Illness; beta-Lactamases; COVID-19; Intensive Care Units; Risk Factors; Klebsiella pneumoniae; Prognosis
PubMed: 38641851
DOI: 10.1186/s13054-024-04906-2 -
Digestive Diseases and Sciences Jun 2024Many women grow up dreaming of becoming doctors, preferring specialties that allow more focus on time outside the hospital and on family life. Nowadays, specialties,...
BACKGROUND
Many women grow up dreaming of becoming doctors, preferring specialties that allow more focus on time outside the hospital and on family life. Nowadays, specialties, like gastroenterology, have still a significant gender gap.
METHODS
Based on this known discrepancy, a web-based questionnaire was designed by the Young Component of the Scientific Committee of the Federation of Italian Scientific Societies of Digestive Diseases 2023 (FISMAD) to examine the current situation of female gastroenterologists in Italy. The survey, designed specifically for this study, was sent by email to all female gastroenterologists and residents gastroenterologists, members of the three major Italian societies of Gastroenterology.
RESULTS
A total of 423 female physicians responded to the survey: 325 (76.8%) had full-time employment, and only a few had an academic career (7.2%). The main occupations were outpatient clinics (n = 288, 68%) and diagnostic endoscopy (n = 289, 68.3%); only 175 (41.3%) performed interventional endoscopy. One hundred and forty-seven (34.7%) had the chance to attend a master in advanced or interventional endoscopy, while 133 (31.4%) faced disadvantages that enabled them to attend. Of the 244 (58%) who reported feeling underappreciated, 194 (79.5%) said it was due to gender bias. We found that women doctors considered themselves disadvantaged compared with men doctors due to career opportunities (n = 338), salary negotiations (n = 64), and training opportunities (n = 144).
CONCLUSIONS
In conclusion, gastroenterology still has a long way to go before approaching greater gender parity.
Topics: Humans; Female; Italy; Physicians, Women; Gastroenterology; Surveys and Questionnaires; Gastroenterologists; Adult; Middle Aged; Career Choice; Sexism
PubMed: 38637458
DOI: 10.1007/s10620-024-08407-8 -
MethodsX Jun 2024In recent years, eye diseases in diabetic patients are one of the most common has been diabetic retinopathy (DR). which leads to complete blindness in advanced stages....
In recent years, eye diseases in diabetic patients are one of the most common has been diabetic retinopathy (DR). which leads to complete blindness in advanced stages. Diabetes affects the blood vessels in the retina and causes vision loss. One of the ways to decrease the risk of this issue is to detect diabetic retinopathy in its early stages. This study describes a computer-aided screening system (DREAM) that uses a neural network classification model in machine learning to assess fundus images with different illumination and fields of vision and provide a severity grade for diabetic retinopathy. Moreover, the methodology of this study based on:•Enhancement techniques have been used on dataset images, histogram equalization, noise reduction and image scaling,•vSLAM has been selected as feature extraction,•Bilayered Neural Network under resubstitution validation used as a classification model. Finally, after testing on the DR severity grading system is tested on 6332 images of detection of diabetic retinopathy images, the result of the ROC curve is 0.985 on image dataset and obtains accuracy reached 98.5%. The classification result has been founded under MATLAB platform, beside it that be work with real time analysis and detection when patient eyes analysis.
PubMed: 38633420
DOI: 10.1016/j.mex.2024.102705 -
Scientific Reports Apr 2024This study examined the relationship between radon (Rn) concentrations in seawater and crustal activity in the Yatsushiro Sea by investigating the submarine fault zone...
This study examined the relationship between radon (Rn) concentrations in seawater and crustal activity in the Yatsushiro Sea by investigating the submarine fault zone situated at the southern end of the Futagawa-Hinagu fault zone, activated by the 2016 Kumamoto earthquake (M7.3). We conducted an analysis of Rn concentration in samples of bottom water just above the seafloor and pore water in sediments, utilizing multiple and piston cores from the Hakuho Maru Expedition KH18-3. The findings revealed significantly elevated Rn concentrations in the central sites of the Yatsushiro Sea, coinciding with a high-stress field exhibiting dense active faults. Seismicity analysis revealed heightened moment release and a low b-value post the 2016 Kumamoto earthquake, indicative of increased seismic activity and the potential for substantial earthquakes in the Yatsushiro Sea vicinity. Our results indicate that heightened concentrations of Rn in seawater can serve as an effective tracer for identifying and estimating submarine fault activities. Moreover, our research highlights the utility of Rn concentrations in detecting active submarine faults and assessing their activity. It contributes to a comprehensive understanding of the potential for significant earthquakes in the Yatsushiro Sea in the future.
PubMed: 38622234
DOI: 10.1038/s41598-024-59006-6