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PloS One 2024Dogs are often housed alone in shelter settings to reduce injury and disease spread. However, social isolation can be a stressor for dogs. Prior studies have suggested...
Dogs are often housed alone in shelter settings to reduce injury and disease spread. However, social isolation can be a stressor for dogs. Prior studies have suggested that cohousing can produce behavioral and physiological benefits. These studies have typically focused on laboratory dogs or shelter dogs that have been kenneled for several months. Thus, those results might not necessarily generalize to shelter dogs, many of which have shorter lengths of stay than those dogs studied to date, and might be cohoused soon after intake. In fact, being pair-housed could, in the short term, be more stressful as dogs have to navigate novel social situations in small spaces. We investigated the behavioral and physiological effects of single- or pair-housing shelter dogs, most of which had recently entered the shelter. We collected behavioral data on 61 dogs (30 single-housed; 31 pair-housed) daily across seven days; we also collected urine for cortisol:creatinine analysis on a subset (22 single-housed; 18 pair-housed) for eight days (each day of the seven-day study plus a baseline sample on Day 0, prior to dogs' enrollment). We found pair-housed dogs engaged in three stress-related behaviors (lip licking, whining, and ears back) significantly less frequently than single-housed dogs. When we analyzed the change in urinary cortisol:creatinine (Days 1-7 values minus Day 0 value), we found that pair-housed dogs generally showed a greater decrease in cortisol:creatinine levels than single-housed dogs. Pair-housed dogs also had significantly shorter lengths of stay, but we did not detect any effect on dog-dog skills. Overall, we found well-matched pair-housing can have both proximate and ultimate welfare benefits for shelter dogs.
Topics: Animals; Dogs; Behavior, Animal; Animal Welfare; Hydrocortisone; Housing, Animal; Male; Female; Creatinine
PubMed: 38865297
DOI: 10.1371/journal.pone.0301137 -
Drug Design, Development and Therapy 2024Despite its extensive utilization in Chinese hospitals for treating acute pancreatitis (AP) and related acute respiratory distress syndrome (ARDS), the active components...
Mechanism Investigation and Clinical Retrospective Evaluation of Qingyi Granules: Pancreas Cleaner About Ameliorating Severe Acute Pancreatitis with Acute Respiratory Distress Syndrome.
BACKGROUND
Despite its extensive utilization in Chinese hospitals for treating acute pancreatitis (AP) and related acute respiratory distress syndrome (ARDS), the active components and mechanisms underlying the action of Qingyi Granule (QYKL) remain elusive.
METHODS
This study consists of four parts. First, we used Mendelian randomization (MR) to investigate the causal relationship between AP, cytokine, and ARDS. Next, 321 patients were collected to evaluate the efficacy of QYKL combined with dexamethasone (DEX) in treating AP. In addition, we used UHPLC-QE-MS to determine the chemical constituents of QYKL extract and rat serum after the oral administration of QYKL. The weighted gene coexpression network analysis (WGCNA) method was used to find the main targets of AP-related ARDS using the GSE151572 dataset. At last, a AP model was established by retrograde injection of 5% sodium taurocholate.
RESULTS
MR showed that AP may have a causal relationship with ARDS by mediating cytokine storms. Retrospective study results showed early administration of QYKL was associated with a lower incidence of ARDS, mortality, admissions to the intensive care unit, and length of stay in AP patients compared to the Control group. Furthermore, we identified 23 QYKL prototype components absorbed into rat serum. WGCNA and differential expression analysis identified 1558 APALI-related genes. The prototype components exhibited strong binding activity with critical targets. QYKL has a significant protective effect on pancreatic and lung injury in AP rats, and the effect is more effective after combined treatment with DEX, which may be related to the regulation of the IL-6/STAT3 signaling pathway.
CONCLUSION
By integrating MR, retrospective analysis, and systematic pharmacological methodologies, this study systematically elucidated the therapeutic efficacy of QYKL in treating AP-related ARDS, establishing a solid foundation for its medicinal use.
Topics: Drugs, Chinese Herbal; Respiratory Distress Syndrome; Pancreatitis; Animals; Rats; Humans; Retrospective Studies; Male; Rats, Sprague-Dawley; Dexamethasone; Acute Disease; Female; Middle Aged
PubMed: 38863767
DOI: 10.2147/DDDT.S454180 -
Journal of Medical Case Reports Jun 2024Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and... (Review)
Review
BACKGROUND
Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas.
CASE PRESENTATION
A 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis.
REVIEW
Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization.
CONCLUSION
Ectopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present.
Topics: Humans; Female; Adult; Hypogonadism; Adrenocortical Adenoma; Adrenal Cortex Neoplasms; Tomography, X-Ray Computed; Hydrocortisone
PubMed: 38863038
DOI: 10.1186/s13256-024-04595-z -
Science Progress 2024The primary objective of this trial was to study the effects of stress caused by stocking density in tilapia () cultured in the in-pond raceway system (IPRS)....
The primary objective of this trial was to study the effects of stress caused by stocking density in tilapia () cultured in the in-pond raceway system (IPRS). Fingerlings (Initial body weight = 30.00 ± 1.20 g) were reared at different stocking densities i.e. low stocking density (n = 13,000; 1.77 kg/m), medium stocking density (MSD) (n = 17,000; 2.32 kg/m), and high stocking density (HSD) (n = 21,000; 2.86 kg/m), all confined within the raceways of the IPRS. Each group was studied in triplicates. The observed growth revealed a regression in the HSD treatment, evident in its reduced weight gain per fish per day, in contrast to other treatments. Survival rate across all treatments was above 99%. Notably, the HSD treatment exhibited an elevated level of cortisol; however, this intensified crowding stress did not significantly undermine the nutritional value of the fish in HSD and other experimental treatments. Furthermore, an elevation in the levels of superoxide dismutase, catalase, and glutathione peroxidase was noted within the HSD treatment in comparison to the other treatments to reduce the damage caused by reactive oxygen species. As the trial proceeded, functions of digestive enzymes like amylase, protease, and lipase diminished consistently across all treatments. This could possibly signify a deliberate redirection of energy resources toward stress alleviation rather than the usual digestive processes. In summation, it can be reasonably deduced that a stocking density of approximately 2.32 kg/m (MSD) emerges as the optimal threshold for effectively cultivating tilapia within an intensive aquaculture framework.
Topics: Animals; Aquaculture; Tilapia; Population Density; Cichlids; Stress, Physiological; Glutathione Peroxidase; Hydrocortisone; Catalase; Superoxide Dismutase
PubMed: 38860303
DOI: 10.1177/00368504241257128 -
The Journal of Headache and Pain Jun 2024Endogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we...
BACKGROUND
Endogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we investigate the relationship between female sex hormones and Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) concentrations in plasma of women with migraine and healthy controls, aiming to elucidate potential hormonal influences on PACAP dynamics and their relevance to migraine pathophysiology.
METHODS
This analysis is part of a cross-sectional, matched-cohort study. We recruited two groups of women with episodic migraine: one with a regular menstrual cycle (M-RMC) and another undergoing combined oral contraceptive treatment (M-COC). Additionally, we included corresponding age-matched control groups without migraine for both categories (C-RMC and C-COC). For participants with a RMC, the study visits were scheduled during the perimenstrual period (menstrual cycle day 2 ± 2) and periovulatory period (day 13 ± 2). Participants using COC were examined at day 4 ± 2 of the hormone-free interval and between day 7-14 of the hormone intake phase. During these visits, PACAP-38 concentrations in plasma were measured using a commercial Enzyme-linked-immunosorbent assay (ELISA) kit.
RESULTS
The study included 120 women, with 30 participants in each group. Women with migraine and a RMC had significantly higher PACAP-38 plasma concentrations compared to healthy controls at both study visits [day 2 ± 2: M-RMC: 2547.41 pg/ml (IQR 814.27 - 4473.48) vs. C-RMC: 1129.49 pg/ml (IQR 257.34 - 2684.88), p = 0.025; day 13 ± 2: M-RMC: 3098.89 pg/ml (IQR 1186.29 - 4379.47) vs. C-RMC: 1626.89 (IQR 383.83 - 3038.36), p = 0.028]. In contrast, PACAP-38 levels were comparable between migraine and control groups receiving COC. Women with migraine and a RMC exhibited higher PACAP-38 concentrations during menstruation compared to those using COC during the hormone-free interval.
CONCLUSION
Systemic PACAP-38 concentrations in women vary based on the presence of migraine diagnosis and their hormonal status.
Topics: Humans; Female; Migraine Disorders; Cross-Sectional Studies; Pituitary Adenylate Cyclase-Activating Polypeptide; Adult; Cohort Studies; Menstrual Cycle; Young Adult; Gonadal Steroid Hormones; Contraceptives, Oral, Combined; Estradiol; Progesterone
PubMed: 38858641
DOI: 10.1186/s10194-024-01804-4 -
BMC Neurology Jun 2024The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety.
METHODS
A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators.
RESULTS
A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544).
CONCLUSION
Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results.
TRIAL REGISTRATION
Retrospectively registered in PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .
Topics: Humans; Tuberculosis, Meningeal; Dexamethasone; Isoniazid; Antitubercular Agents; Drug Therapy, Combination; Injections, Spinal; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38858618
DOI: 10.1186/s12883-024-03701-4 -
Nature Communications Jun 2024Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic...
Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic synapses in medial prefrontal cortic (mFPC) neurons. Ketamine induced profound changes in a number of molecular pathways in a mouse model for chronic stress. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling was decreased after chronic administration of corticosterone but increased following ketamine administration in most of the excitatory neurons. Similar decrease of PCP signaling in excitatory neurons was predicted in dorsolateral prefrontal cortical (dl-PFC) neurons of patients with major depressive disorder (MDD). We showed that the basolateral amygdala (BLA)-projecting infralimbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Conditionally knocking out Celsr2 and Celsr3 or Prickle2 in the BLA-projecting IL PFC neurons abolished ketamine-induced synapse restoration and behavioral remission. Therefore, PCP proteins in IL PFC-BLA neurons mediate synapse restoration induced by of low-dose ketamine.
Topics: Animals; Ketamine; Prefrontal Cortex; Synapses; Neurons; Mice; Disease Models, Animal; Male; Humans; Cell Polarity; Depressive Disorder, Major; Mice, Knockout; Stress, Psychological; Corticosterone; Basolateral Nuclear Complex; Mice, Inbred C57BL; LIM Domain Proteins; Glutamic Acid; Antidepressive Agents
PubMed: 38858386
DOI: 10.1038/s41467-024-48257-6 -
Environment International Jul 2024A significant challenge in the traditional human health risk assessment of agrochemicals is the uncertainty in quantifying the interspecies differences between animal...
A significant challenge in the traditional human health risk assessment of agrochemicals is the uncertainty in quantifying the interspecies differences between animal models and humans. To work toward a more accurate and animal-free risk determination, new approaches such as physiologically based kinetic (PBK) modeling have been used to perform dosimetry extrapolation from animals to humans. However, the regulatory use and acceptance of PBK modeling is limited for chemicals that lack in vivo animal pharmacokinetic (PK) data, given the inability to evaluate models. To address these challenges, this study developed PBK models in the absence of in vivo PK data for the fungicide propiconazole, an activator of constitutive androstane receptor (CAR)/pregnane X receptor (PXR). A fit-for-purpose read-across approach was integrated with hierarchical clustering - an unsupervised machine learning algorithm, to bridge the knowledge gap. The integration allowed the incorporation of a broad spectrum of attributes for analog consideration, and enabled the analog selection in a simple, reproducible, and objective manner. The applicability was evaluated and demonstrated using penconazole (source) and three pseudo-unknown target chemicals (epoxiconazole, tebuconazole and triadimefon). Applying this machine learning-enhanced read-across approach, difenoconazole was selected as the most appropriate analog for propiconazole. A mouse PBK model was developed and evaluated for difenoconazole (source), with the mode of action of CAR/PXR activation incorporated to simulate the in vivo autoinduction of metabolism. The difenoconazole mouse model then served as a template for constructing the propiconazole mouse model. A parallelogram approach was subsequently applied to develop the propiconazole rat and human models, enabling a quantitative assessment of interspecies differences in dosimetry. This integrated approach represents a substantial advancement toward refining risk assessment of propiconazole within the framework of animal alternative safety assessment strategies.
Topics: Triazoles; Animals; Machine Learning; Fungicides, Industrial; Humans; Risk Assessment; Models, Biological; Mice; Kinetics
PubMed: 38857551
DOI: 10.1016/j.envint.2024.108804 -
Scientific Reports Jun 2024Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4...
Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases.
Topics: Humans; Male; Hypertension; Receptors, G-Protein-Coupled; Animals; Receptors, Peptide; Rats; Female; Antibodies, Monoclonal; Adrenal Glands; Drug Resistance; Antihypertensive Agents; Aldosterone
PubMed: 38851835
DOI: 10.1038/s41598-024-62804-7 -
Respiratory Medicine 2024Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs)... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event.
OBJECTIVE
We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed.
METHODS
This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV) were randomized to receive Salbutamol Easyhaler (2 × 200 μg), Ventoline Evohaler with spacer (4 × 100 μg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 μg) as a reliever. The treatment was repeated if FEV did not recover to at least -10 % of baseline.
RESULTS
180 participants (69 % females, mean age 46 yrs [range 18-80], FEV%pred 89.5 [62-142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a -0.083 (95 % LCL -0.146) L FEV difference after the first dose and -0.032 (-0.071) L after the last dose. The differences in FEV between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were -0.163 (-0.225) L after the first and -0.092 (-0.131) L after the last dose.
CONCLUSION
The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.
Topics: Humans; Methacholine Chloride; Female; Bronchoconstriction; Male; Adult; Asthma; Middle Aged; Albuterol; Dry Powder Inhalers; Forced Expiratory Volume; Bronchodilator Agents; Young Adult; Administration, Inhalation; Metered Dose Inhalers; Adolescent; Bronchial Provocation Tests; Treatment Outcome; Aged; Inhalation Spacers; Budesonide, Formoterol Fumarate Drug Combination
PubMed: 38851404
DOI: 10.1016/j.rmed.2024.107693