Secondary adrenocortical insufficiency after treatment with retifanlimab: a case report

With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency

Infrared Drying as a Quick Preparation Method for Dried Tangerine Peel

To establish the most convenient and effective method to dry tangerine peels, different methods (sun drying, hot-air drying, freeze drying, vacuum drying, and medium- and short-wave infrared drying) were exploited. Our results indicated that medium- and short-wave infrared drying was the best method to preserve nutraceutical components; for example, vitamin C was raised to 6.77 mg/g (D.W.) from 3.39 mg/g (sun drying). Moreover, the drying time can be shortened above 96% compared with sun drying. Importantly, the efficiency of DPPH radical scavenging was enhanced from 26.66% to 55.92%. These findings would provide a reliable and time-saving methodology to produce high-quality dried tangerine peels

A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken

Author summaryVertebrates possess two types of melanin, red/yellow pheomelanin and black/brown eumelanin. In this study, we report that the recessive Inhibitor of gold phenotype in chicken, which causes a severe defect in pheomelanin pigmentation, is associated with a mutation that most likely inactivates the COMTD1 gene. This gene encodes an O-methyltransferase enzyme and is present throughout vertebrate evolution, but is one of the many genes in vertebrate genomes for which the biological function is still poorly understood. This is the first report of a COMTD1 mutation associated with a phenotypic effect. We show that the COMTD1 protein is present in mitochondria in pigment cells. Furthermore, inactivation of the gene in a mouse pigment cell line results in a significant reduction in metabolites that are important for the synthesis of pheomelanin. We hypothesize that COMTD1 activity protects pigment cells from oxidative stress and that inactivation of this function impairs the production of pheomelanin. It is likely that COMTD1 has a similar function in other cell types. This study establishes this chicken mutation as a model for further studies of COMTD1 function.The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive allele (IG) at this locus is associated with a defect in the production of pheomelanin. IG/IG homozygotes display a marked dilution of red pheomelanin pigmentation, whilst black pigmentation (eumelanin) is only slightly affected. Here we show that a 2-base pair insertion (frame-shift mutation) in the 5(th) exon of the Catechol-O-methyltransferase containing domain 1 gene (COMTD1), expected to cause a complete or partial loss-of-function of the COMTD1 enzyme, shows complete concordance with the IG phenotype within and across breeds. We show that the COMTD1 protein is localized to mitochondria in pigment cells. Knockout of Comtd1 in a mouse melanocytic cell line results in a reduction in pheomelanin metabolites and significant alterations in metabolites of glutamate/glutathione, riboflavin, and the tricarboxylic acid cycle. Furthermore, COMTD1 overexpression enhanced cellular proliferation following chemical-induced transfection, a potential inducer of oxidative stress. These observations suggest that COMTD1 plays a protective role for melanocytes against oxidative stress and that this supports their ability to produce pheomelanin

Alterations in brain structure and function associated with pediatric growth hormone deficiency: A multi-modal magnetic resonance imaging study

IntroductionPediatric growth hormone deficiency (GHD) is a disease resulting from impaired growth hormone/insulin-like growth factor-1 (IGF-1) axis but the effects of GHD on children’s cognitive function, brain structure and brain function were not yet fully illustrated.MethodsFull Wechsler Intelligence Scales for Children, structural imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were assessed in 11 children with GHD and 10 matched healthy controls.Results(1) The GHD group showed moderate cognitive impairment, and a positive correlation existed between IGF-1 levels and cognitive indices. (2) Mean diffusivity was significantly increased in both corticospinal tracts in GHD group. (3) There were significant positive correlations between IGF-1 levels and volume metrics of left thalamus, left pallidum and right putamen but a negative correlation between IGF-1 levels and cortical thickness of the occipital lobe. And IGF-1 levels negatively correlated with fractional anisotropy in the superior longitudinal fasciculus and right corticospinal tract. (4) Regional homogeneity (ReHo) in the left hippocampus/parahippocampal gyrus was negatively correlated with IGF-1 levels; the amplitude of low-frequency fluctuation (ALFF) and ReHo in the paracentral lobe, postcentral gyrus and precentral gyrus were also negatively correlated with IGF-1 levels, in which region ALFF fully mediates the effect of IGF-1 on working memory index.ConclusionMultiple subcortical, cortical structures, and regional neural activities might be influenced by serum IGF-1 levels. Thereinto, ALFF in the paracentral lobe, postcentral gyrus and precentral gyrus fully mediates the effect of IGF-1 on the working memory index

CNS-LAND score: predicting early neurological deterioration after intravenous thrombolysis based on systemic responses and injury

ImportanceEarly neurological deterioration (END) is a critical complication in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT), with a need for reliable prediction tools to guide clinical interventions.ObjectiveThis study aimed to develop and validate a rating scale, utilizing clinical variables and multisystem laboratory evaluation, to predict END after IVT.Design, setting, and participantsThe Clinical Trial of Revascularization Treatment for Acute Ischemic Stroke (TRAIS) cohort enrolled consecutive AIS patients from 14 stroke centers in China (Jan 2018 to Jun 2022).OutcomesEND defined as NIHSS score increase >4 points or death within 24 h of stroke onset.Results1,213 patients (751 in the derivation cohort, 462 in the validation cohort) were included. The CNS-LAND score, a 9-point scale comprising seven variables (CK-MB, NIHSS score, systolic blood pressure, LDH, ALT, neutrophil, and D-dimer), demonstrated excellent differentiation of END (derivation cohort C statistic: 0.862; 95% CI: 0.796–0.928) and successful external validation (validation cohort C statistic: 0.851; 95% CI: 0.814–0.882). Risk stratification showed END risks of 2.1% vs. 29.5% (derivation cohort) and 2.6% vs. 31.2% (validation cohort) for scores 0–3 and 4–9, respectively.ConclusionCNS-LAND score is a reliable predictor of END risk in AIS patients receiving IVT

Stability of SARS-CoV-2 in cold-chain transportation environments and the efficacy of disinfection measures

BackgroundLow temperature is conducive to the survival of COVID-19. Some studies suggest that cold-chain environment may prolong the survival of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and increase the risk of transmission. However, the effect of cold-chain environmental factors and packaging materials on SARS-CoV-2 stability remains unclear.MethodsThis study aimed to reveal cold-chain environmental factors that preserve the stability of SARS-CoV-2 and further explore effective disinfection measures for SARS-CoV-2 in the cold-chain environment. The decay rate of SARS-CoV-2 pseudovirus in the cold-chain environment, on various types of packaging material surfaces, i.e., polyethylene plastic, stainless steel, Teflon and cardboard, and in frozen seawater was investigated. The influence of visible light (wavelength 450 nm-780 nm) and airflow on the stability of SARS-CoV-2 pseudovirus at -18°C was subsequently assessed.ResultsExperimental data show that SARS-CoV-2 pseudovirus decayed more rapidly on porous cardboard surfaces than on nonporous surfaces, including polyethylene (PE) plastic, stainless steel, and Teflon. Compared with that at 25°C, the decay rate of SARS-CoV-2 pseudovirus was significantly lower at low temperatures. Seawater preserved viral stability both at -18°C and with repeated freeze−thaw cycles compared with that in deionized water. Visible light from light-emitting diode (LED) illumination and airflow at -18°C reduced SARS-CoV-2 pseudovirus stability.ConclusionOur studies indicate that temperature and seawater in the cold chain are risk factors for SARS-CoV-2 transmission, and LED visible light irradiation and increased airflow may be used as disinfection measures for SARS-CoV-2 in the cold-chain environment

A modality selective effect of functional laterality in pain detection sensitivity

The ability to detect environmental changes is essential to determine the appropriate reaction when facing potential threats. Both detection and reaction functions are critical to survival, and the superior performance of motor reaction for the dominant hand is well recognized in humans. However, it is not clear whether there exists laterality in sensitivity to detect external changes and whether the possible laterality is associated with sensory modality and stimulus intensity. Here, we tested whether the perceptual sensitivity and electrophysiological responses elicited by graded sensory stimuli (i.e., nociceptive somatosensory, non-nociceptive somatosensory, auditory, and visual) that were delivered on/near the left and right hands would be different for right-handed individuals. We observed that perceived intensities and most brain responses were significantly larger when nociceptive stimuli were delivered to the left side (i.e., the non-dominant hand) than to the right side (i.e., the dominant hand). No significant difference was observed between the two sides for other modalities. The higher sensitivity to detect nociceptive stimuli for the non-dominant hand would be important to provide a prompt reaction to noxious events, thus compensating for its worse motor performance. This laterality phenomenon should be considered when designing experiments for pain laboratory studies and evaluating regional sensory abnormalities for pain patients.</p

A Comprehensive Review of Energy Regeneration and Conversion Technologies Based on Mechanical–Electric–Hydraulic Hybrid Energy Storage Systems in Vehicles

The primary purpose of this paper is to investigate energy regeneration and conversion technologies based on mechanical–electric–hydraulic hybrid energy storage systems in vehicles. There has been renewed interest in hydraulic storage systems since evidence has been presented that shows that they have the distinct advantages of high energy output and energy recuperation compared to electrical energy recovery systems, which are widely applied in electric vehicles; however, they are known to be high-cost, with a complicated structure and not zero carbon. In this paper, we first review recent research on hydraulic energy regeneration and conversion technologies. Secondly, as the main part of this paper, the latest technological progress and breakthroughs of the mechanical–electric–hydraulic hybrid energy storage systems in vehicles—which are divided into four categories: passenger, minibus and bus, commercial vehicle and special vehicle—are analyzed and discussed in depth. In addition, the current research status of energy management techniques is presented and summarized. Finally, prospects and challenges are suggested and explained. It is evident from the literature review that the mechanical–electric–hydraulic hybrid systems perform excellently in vehicles. Clearly, this review will be helpful to understand, explore and define the hydraulic vehicle of the future concerning energy optimization and environmental friendliness

The role of negative emotions in sex differences in pain sensitivity

Pain perception&nbsp;varies widely among individuals due to the varying degrees of biological, psychological, and social factors. Notably, sex differences in pain sensitivity have been consistently observed in various experimental and clinical investigations. However, the neuropsychological mechanism underlying sex differences in pain sensitivity remains unclear. To address this issue, we quantified pain sensitivity (i.e., pain threshold and tolerance) using the cold pressure test and negative emotions (i.e., pain-related fear, pain-related anxiety, trait anxiety, and depression) using well-established questionnaires and collected magnetic resonance imaging (MRI) data (i.e., high-resolution T1 structural images and resting-state functional images) from 450 healthy subjects. We observed that, as compared to males, females exhibited lower pain threshold and tolerance. Notably, sex differences in pain sensitivity were mediated by pain-related fear and anxiety. Specifically, pain-related fear and anxiety were the complementary mediators of the relationship between sex and pain threshold, and they were the indirect-only mediators of the relationship between sex and pain tolerance. Besides,&nbsp;structural MRI&nbsp;data revealed that the&nbsp;amygdala&nbsp;subnuclei (i.e., the lateral and&nbsp;basal nuclei&nbsp;in the left hemisphere) volumes were the complementary mediators of the relationship between sex and pain-related fear, which further influenced pain sensitivity. Altogether, our results provided a comprehensive picture of how negative emotions (especially pain-related negative emotions) and related brain structures (especially the amygdala) contribute to sex differences in pain sensitivity. These results deepen our understanding of the neuropsychological underpinnings of sex differences in pain sensitivity, which is important to tailor a personalized method for treating pain according to sex and the level of pain-related negative emotions for patients with painful conditions.</p