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Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy.Nature Communications Jan 2024ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic...
ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic variability that has not been molecularly explained yet. In brain amyloid conditions, previous studies suggest an association between clinical phenotype and the molecular structures of their amyloid fibrils. Here we investigate whether there is such an association in ATTRv amyloidosis patients carrying the mutation I84S. Using cryo-electron microscopy, we determined the structures of cardiac fibrils extracted from three ATTR amyloidosis patients carrying the ATTRv-I84S mutation, associated with a consistent clinical phenotype. We found that in each ATTRv-I84S patient, the cardiac fibrils exhibited different local conformations, and these variations can co-exist within the same fibril. Our finding suggests that one amyloid disease may associate with multiple fibril structures in systemic amyloidoses, calling for further studies.
Topics: Humans; Amyloid; Amyloid Neuropathies, Familial; Cryoelectron Microscopy; Prealbumin; Heart; Brain Diseases
PubMed: 38233397
DOI: 10.1038/s41467-024-44820-3 -
African Health Sciences Jun 2023Preterm birth is one of the most important health problems in the world. Feeding intolerance is one of the most common and serious complications of premature infant. The... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Preterm birth is one of the most important health problems in the world. Feeding intolerance is one of the most common and serious complications of premature infant. The purpose of this study was to explore the effect of Chinese pediatric Tuina on the prevention of feeding intolerance in favour of weight gain in premature infants.
METHODS
A prospective randomized controlled study was conducted in the Department of Neonatology in our hospital. Premature infants were recruited and randomly assigned to an intervention group or a control group. Premature infants in the intervention group received a Chinese pediatric Tuina intervention by professional chiropractors, while premature infants in the control group received standard care. The incidence of feeding intolerance and weight gain situation were compared between the two groups.
RESULT
After 1 week of intervention, the body weight (2.5±0.5 vs 2.0±0.4, p=0.038), head circumference (32.8±1.7 vs 29.9±1.4, p=0.041), albumin (34.6±5.8 vs 28.4±6.1, p-0.026) and prealbumin (155.8±35.2 vs 113.6±36.8, p=0.021) of preterm infants in the intervention group were significantly better than those in the control group. The incidence of feeding intolerance (7 vs 15, p=0.032) in the intervention group was significantly lower than that in the control group. Although there were no statistically significant differences (P>0.05), the incidences of gastrointestinal bleeding, necrotizing enterocolitis, and liver insufficiency were lower in the intervention group than in the control group.
CONCLUSION
Chinese pediatric Tuina can effectively prevent the occurrence of feeding intolerance in premature infants and be conducive to the weight gain and improving nutritional status of premature infants.
Topics: Humans; Infant, Newborn; China; Infant, Premature; Premature Birth; Prospective Studies; Weight Gain
PubMed: 38223605
DOI: 10.4314/ahs.v23i2.80 -
Gerontology & Geriatric Medicine 2024Malnutrition is a significant issue among elderly individuals in 24-hour care facilities, leading to increased morbidity. The aim of the study was to compare the...
Malnutrition is a significant issue among elderly individuals in 24-hour care facilities, leading to increased morbidity. The aim of the study was to compare the nutritional status before and after nutritional intervention based on selected indicators of nutritional status among residents of a 24-hour care institution. The study included a group of 104 people aged 65 to 97 years. Nutritional status was assessed before and after the nutritional intervention based on indicators: levels of prealbumin, albumin, transferrin, total lymphocyte count, BMI, and MNA scale. The nutritional intervention consisted of administering oral nutritional supplements (ONS) to patients, regardless of nutritional status. The method of retrospective analysis of patients' medical records was used. Statistical analysis was performed using IBM SPSS Statistics 24 for Windows. Improvements in nutritional status occurred among patients with malnutrition based on MNA and prealbumin indices, and in groups of patients with moderate or mild malnutrition as determined by transferrin, prealbumin and albumin. The mean levels of nutritional indices significantly increased: MNA ( = .001), BMI ( = .001), prealbumin ( = .001), and albumin ( < .001). The use of ONS resulted in better nutritional status parameters based on MNA, albumin and prealbumin. These indices may be predictors of reducing the risk of various disorders among the elderly.
PubMed: 38223549
DOI: 10.1177/23337214231224574 -
World Journal of Gastrointestinal... Dec 2023Radiation enteritis, which often occurs during radiation-induced acute intestinal symptoms (RIAIS), is the most common and important complication during radiotherapy for...
BACKGROUND
Radiation enteritis, which often occurs during radiation-induced acute intestinal symptoms (RIAIS), is the most common and important complication during radiotherapy for cervical cancer. RIAIS caused by abdominal and pelvic radiotherapy will affect nutrient intake, digestion, absorption, and metabolism, leading to malnutrition or poorer nutritional status. In patients with malignant tumors, malnutrition can adversely affect the curative effect and response of radiotherapy by reducing radiosensitivity, affecting the precision of radiotherapy placement and increasing the incidence of radiotherapy-related adverse reactions.
AIM
To analyze nutritional risk, skeletal muscle depletion, and lipid metabolism phenotype in acute radiation enteritis.
METHODS
Fifty patients with cervical cancer received external beam radiotherapy, and 15 patients received brachytherapy after external beam radiotherapy. Body weight, body composition parameters, nutritional risk screening (NRS) 2002 score, and blood biochemical indices of patients with cervical cancer during periradiation were tested by a one-way repeated measures analysis of variance. Metabolomics analysis was used to identify characteristic lipid metabolism pathways. Clinical factors that affect linoleic acid changes were screened using the generalized evaluation equation.
RESULTS
Among the 50 patients, 37 had RIAIS, including 34 patients with grade 1-2 RIAIS and 3 patients with grade 3 RIAIS. The NRS 2002 score of patients who underwent cervical cancer radiotherapy continued to increase during the periradiation period, and 42 patients who underwent cancer radiotherapy had nutritional deficits (NRS 2002 score ≥ 3 points) at the end of radiotherapy. Correlation analyses revealed that body weight and body mass index changes were closely associated with body fat content ( = 0.64/0.51). The results of the univariate analysis showed that radiotherapy time, percentage reduction of serum albumin, and percentage reduction of serum prealbumin were the key factors affecting skeletal muscle exhaustion ( < 0.05). Metabolomic analysis of fecal supernatants of cervical cancer patients during the periradiation period revealed the involvement of linoleic acid, cholic acid, arachidonic acid, and N-acetyl-L-benzene alanine in the metabolic pathway of linoleic acid.
CONCLUSION
Cervical cancer radiotherapy patients faced nutritional risks, decreased serum albumin synthesis, and increased risk of skeletal muscle exhaustion. Linoleic acid was a biomarker of high nutritional risk.
PubMed: 38222011
DOI: 10.4240/wjgs.v15.i12.2831 -
World Journal of Gastrointestinal... Dec 2023Study showed that systemic holistic care not only aids in disease treatment and physical recovery to a certain extent but also effectively enhances patient psychological...
BACKGROUND
Study showed that systemic holistic care not only aids in disease treatment and physical recovery to a certain extent but also effectively enhances patient psychological well-being, social support, and overall quality of life (QoL).
AIM
To assess systematic holistic care impact on the recovery and well-being of postoperative patients with colon cancer.
METHODS
Our randomized controlled trial included 98 postoperative patients with colon cancer admitted to our hospital from June 2021 to June 2022. Patients were divided into control and study groups. The control group received conventional postoperative nursing care, whereas the study group received systematic holistic nursing care. We monitored gastrointestinal function recovery, and recorded changes in serum albumin (ALB), prealbumin (PA), psychological state, self-management, self-efficacy, QoL, and the occurrence of complications in patients before, at discharge, and 2 wk post-discharge. Spearman analysis assessed correlations between psychological state, self-management, self-efficacy, and QoL of patients in the study group 2 wk post-discharge.
RESULTS
Following the nursing intervention, we observed significantly shorter postoperative bowel sound recovery time, anal exhaust time, and defecation time in the study group than in the control group ( < 0.05). Patient ALB and PA levels, psychological status, self-management ability, self-efficacy and QoL at discharge and 2 wk post-discharge significantly improved, with greater improvements observed in the study group ( < 0.05). Both groups experienced complications post-interventions, but the intervention group had significantly lower complication rate (3/49, 6.12%) (P < 0.05). In the study group, patient anxiety, depression, self-management and QoL scores at 2 wk post-discharge exhibited a significant negative correlation (3/49, 6.12%) with QoL scores, with correlation coefficients of = -0.273, -0.522, -0.344, and < 0.01, respectively. Conversely, patient self-efficacy scores 2 wk post-discharge showed a positive correlation with QoL scores ( = 0.410, = 0.000).
CONCLUSION
Systemic holistic nursing significantly benefits postoperative patients with colon cancer by promoting gastrointestinal recovery, improving post-operation well-being, reducing complications, and enhancing QoL.
PubMed: 38221998
DOI: 10.4240/wjgs.v15.i12.2844 -
Revista Espanola de Cardiologia... Jun 2024
Topics: Humans; Amyloid Neuropathies, Familial; Male; Female; Middle Aged; Aged; Mass Screening; Adult; Spain; Prealbumin; Genetic Testing
PubMed: 38220055
DOI: 10.1016/j.rec.2023.12.006 -
Journal of the American Heart... Jan 2024Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to...
Use of Technetium-99m-Pyrophosphate Single-Photon Emission Computed Tomography/Computed Tomography in Monitoring Therapeutic Changes of Eplontersen in Patients With Hereditary Transthyretin Amyloid Cardiomyopathy.
BACKGROUND
Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Recent evidence indicates that bone scintigraphy may serve as a tool to monitor the effectiveness of hATTR-CM treatment. The objective of this study was to examine how eplontersen therapy influences the semiquantitative uptake of technetium-99m-pyrophosphate in individuals diagnosed with hATTR-CM.
METHODS AND RESULTS
We retrospectively analyzed a prospective cohort from the NEURO-TTRansform trial, including patients with hATTR-CM receiving eplontersen (45 mg/4 weeks). A control group comprised patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis, or patisiran. Technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography was conducted at baseline and during follow-up. Thirteen patients with hATTR-CM were enrolled, with 6 receiving eplontersen and 7 serving as the control group. The median follow-up time was 544 days. The eplontersen group exhibited a significant decrease in volumetric heart and lung ratio (3.774 to 2.979, =0.028), whereas the control group showed no significant change (4.079 to 3.915, =0.237). Patients receiving eplontersen demonstrated a significantly greater reduction in volumetric heart and lung ratio compared with the control group (-20.7% versus -3.4%, =0.007).
CONCLUSIONS
The volumetric heart and lung ratio used to quantify technetium-99m-pyrophosphate uptake showed a significant reduction subsequent to eplontersen treatment in individuals diagnosed with hATTR-CM. These findings suggest the potential efficacy of eplontersen in treating hATTR-CM and highlight the value of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography as a tool for monitoring therapeutic effectiveness.
Topics: Humans; Amyloid Neuropathies, Familial; Cardiomyopathies; Prealbumin; Prospective Studies; Retrospective Studies; Technetium Tc 99m Pyrophosphate; Tomography, X-Ray Computed
PubMed: 38214277
DOI: 10.1161/JAHA.123.030512 -
Medicine Dec 2023To investigate the correlation between serum thyroid-stimulating hormone (TSH) levels and glycolipid metabolism in patients with polycystic ovary syndrome (PCOS). From...
To investigate the correlation between serum thyroid-stimulating hormone (TSH) levels and glycolipid metabolism in patients with polycystic ovary syndrome (PCOS). From January 2021 to November 2022, 105 patients with PCOS were selected for this retrospective study. All patients were administered drug-induced ovulation treatment and were divided into 2 groups according to ovulation status. There were 67 and 38 patients in the ovulation and non-ovulation groups, respectively. Venous blood (5 mL) was collected on the day after admission from the non-ovulation group and on the day of physical examination from the ovulation group. Several indicators were measured, including TSH, fasting plasma glucose (FPG), glycosylated hemoglobin, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride (TG), albumin (ALB), prealbumin (PA), and transferrin (TF). Weight, BMI, waistline, and hipline in the non-ovulation group were significantly higher than those in the ovulation group (P < .05). There were no significant differences in glycosylated hemoglobin, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels between the non-ovulation and ovulation groups (P > .05). Compared with the ovulation group, the levels of TSH, FPG, TC, and TG in the non-ovulation group were significantly higher (P < .05). Serum ALB, PA, and TF the non-ovulation group were significantly higher than those in the ovulation group (P < .05). Correlation analysis showed that TSH was negatively correlated with weight, BMI, waistline, hipline, waist-hip ratio, FPG, ALB, PA, and TF in the non-ovulation group (P < .05) and had no significant correlation with TC and TG (P > .05). Our findings demonstrate TSH levels may be associated with weight, BMI, waistline, hipline, waist-hip ratio, FPG, ALB, PA, and TF in patients with PCOS.
Topics: Female; Humans; Polycystic Ovary Syndrome; Retrospective Studies; Glycated Hemoglobin; Triglycerides; Cholesterol, LDL; Cholesterol, HDL; Thyrotropin; Glycolipids; Body Mass Index; Insulin Resistance
PubMed: 38206696
DOI: 10.1097/MD.0000000000036791 -
ESC Heart Failure Apr 2024Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by increased wall thickness, diastolic dysfunction and progressive heart failure symptoms. The disease...
AIMS
Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by increased wall thickness, diastolic dysfunction and progressive heart failure symptoms. The disease may infiltrate the conduction system leading to conduction disturbances requiring an implantation of permanent cardiac pacemaker (PM), but the extent is unknown. Here, we report the prevalence of ATTR-CM in patients ≥65 years with PM.
METHODS AND RESULTS
In this prospective, cross-sectional single-centre study patients were recruited from our out-patient pacemaker clinic. Eligibility criteria were age above 65 years, permanent cardiac pacemaker and competent to give informed consent. Patients underwent echocardiography at the pacemaker visit and were referred to Tc-DPD-scintigraphy (DPD) and blood samples if septum thickness was ≥12 mm, defined as left ventricular hypertrophy (LVH). Fifty eight of the 128 patients had LVH on echocardiography. Eleven patients had a DPD-scintigraphy based diagnosis of ATTR-CM, which represent 19% of patients with LVH and 9% of the total cohort. Patients diagnosed with ATTR-CM had higher concentrations of cardiac biomarkers (P < 0.001), higher E/E' (P = 0.001), and lower global longitudinal strain (P = 0.003) on echocardiography and more heart failure symptoms (P = 0.001).
CONCLUSIONS
The prevalence of ATTR-CM in elderly patients with PM and LVH on echocardiography was 19%.
Topics: Humans; Aged; Prealbumin; Amyloid Neuropathies, Familial; Prospective Studies; Prevalence; Cross-Sectional Studies; Cardiomyopathies; Heart Diseases; Heart Failure; Hypertrophy, Left Ventricular; Pacemaker, Artificial
PubMed: 38204282
DOI: 10.1002/ehf2.14645 -
International Journal of Molecular... Dec 2023Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations...
Transthyretin (TTR) is an amyloidogenic homotetramer involved in the transport of thyroxine in blood and cerebrospinal fluid. To date, more than 130 TTR point mutations are known to destabilise the TTR tetramer, leading to its extracellular pathological aggregation accumulating in several organs, such as heart, peripheral and autonomic nerves, and leptomeninges. Tolcapone is an FDA-approved drug for Parkinson's disease that has been repurposed as a TTR stabiliser. We characterised 3-O-methyltolcapone and two newly synthesized lipophilic analogues, which are expected to be protected from the metabolic glucuronidation that is responsible for the lability of tolcapone in the organism. Immunoblotting assays indicated the high degree of TTR stabilisation, coupled with binding selectivity towards TTR in diluted plasma of 3-O-methyltolcapone and its lipophilic analogues. Furthermore, in vitro toxicity data showed their several-fold improved neuronal and hepatic safety compared to tolcapone. Calorimetric and structural data showed that both T4 binding sites of TTR are occupied by 3-O-methyltolcapone and its lipophilic analogs, consistent with an effective TTR tetramer stabilisation. Moreover, in vitro permeability studies showed that the three compounds can effectively cross the blood-brain barrier, which is a prerequisite for the inhibition of TTR amyloidogenesis in the cerebrospinal fluid. Our data demonstrate the relevance of 3-O-methyltolcapone and its lipophilic analogs as potent inhibitors of TTR amyloidogenesis.
Topics: Tolcapone; Prealbumin; Benzophenones; Autonomic Pathways
PubMed: 38203650
DOI: 10.3390/ijms25010479