BACKGROUND

Observational studies have increasingly reported transthyretin amyloid cardiomyopathy (ATTR-CM) as an under-recognized cause of heart failure. We report the first ATTR-CM diagnosed via multi-modality imaging in the Philippines signifying an important milestone in recognition and management of this formerly believed rare disease, locally. Utilization of non-invasive imaging such as echocardiography, cardiac MRI and technetium-99m pyrophosphate scintigraphy (PYP) demonstrates the potential for accurate diagnosis as well as timely and appropriate treatment strategies.

An 81/M Filipino with a history of carpal tunnel surgery, post-percutaneous coronary intervention (PCI), had three months’ history of refractory heart failure symptoms despite optimized medical treatment. His 2D-echo showed an ejection fraction (EF): 45%-50%, increased left ventricular (LV) posterior wall thickness with mild basal inferior wall hypokinesia and ECG: atrial fibrillation with low voltage. Speckle tracking imaging showed average global longitudinal strain: - 6.5% with cherry-on-top pattern on polar strain map. Cardiac MRI demonstrated diffuse late gadolinium enhancement from endocardial to transmural layers of biventricular and biatrial walls, highly suggestive of cardiac amyloidosis (CA). Light-chain amyloidosis was excluded by negative serum/urine protein electrophoresis/immunofixation. Tc-99m PYP scan revealed greater myocardial-than-bone uptake with a Perugini score 3 and calculated heart-to-contralateral ratio of 1.7. Congestion was controlled with intravenous loop diuretics and he was discharged stable with metoprolol succinate, dapagliflozin and apixaban. At the time of paper submission, he is currently being evaluated for tafamidis treatment.

The case highlighted the advantage of multi-modality imaging for noninvasive yet accurate identification of the disease. A tailored approach is required in slowing the disease progression and improving outcomes.

Although salt-related behaviors may influence urinary salt excretion in early childhood, this relationship remains unclear. This study aimed to examine salt-related behaviors using data from a salt check sheet and urinary salt excretion parameters using spot urine samples from 4-year-old children. This cross-sectional study included all 4-year-old children who underwent health checkups in Ohnan Town, Shimane Prefecture. The study sample consisted of 109 children (49 boys). Measures from spot urine samples included estimated salt excretion (g/day) and the sodium-potassium (Na/K) ratio. Salt-related behaviors were assessed using a salt check sheet that was completed by the parents or guardians. The associations between salt-related behaviors and urinary salt excretion parameters were analyzed using a generalized linear model. The median (M) and interquartile range (IQR) for urinary measures in 4-year-old children were as follows: estimated salt excretion (M = 4.4, IQR: 3.3-6.2) and Na/K ratio (M = 2.3, IQR: 1.4-3.3). The low frequency of consumption of high-salt foods ("such as pickles, pickled plums, etc." and "noodles such as udon and ramen") was associated with low salt excretion and low Na/K ratio. However, in the case of "consumption of udon, ramen, or other soups", the Na/K ratio was higher for "About half a bowl" and "Some" than for "An entire bowl." Additionally, for "eating out or having convenience-store-bought bento (lunch plate) for lunch", the Na/K ratio was higher for "No" than for "Almost every day." In conclusion, the frequency of high-sodium food intake was associated with both urinary sodium excretion and the Na/K ratio in 4-year-old children. Longitudinal investigations using the 24-hour urine collection method are needed to confirm these salt-related behaviors.
Humans ; Child, Preschool ; Male ; Cross-Sectional Studies ; Female ; Sodium Chloride, Dietary/urine* ; Parents ; Sodium/urine* ; Japan ; Potassium/urine*

Objective To investigate the effect of liquid-liquid phase separation(LLPS)of YTH domain family protein 2(YTHDF2)on the sodium arsenite-induced malignant transformation of skin cells,providing a new intervention target for the prevention and control of sodium arsenite-induced carcinogenesis.Methods The HaCaT cell model of malignant transformation was constructed by continuous treatment with 1 μmol/L sodium arsenite for 22 weeks,including cells with normal YTHDF2 LLPS(YTHDF2-wt)and cells with inhibited YTHDF2 LLPS(YTHDF2-mut).Confocal microscopy was employed to observe and characterize the LLPS droplets formed by YTHDF2 during sodium arsenite-induced malignant transformation of skin cells.Cell proliferation,scratch healing,and colony formation assays were performed to detect malignant phenotypes.Western blotting,quantitative reverse transcription PCR,and immunofluorescence experiments were conducted to examine the effects of YTHDF2 LLPS on the mRNA and protein levels of phosphatase and tensin homolog deleted on chromosome ten(PTEN)during sodium arsenite-induced malignant transformation of skin cells.Results After 4 weeks of sodium arsenite treatment,LLPS droplets of YTHDF2 appeared in YTHDF2-wt cells,and the number of droplets gradually increased as the treatment time was prolonged(F=35.252,P<0.001),while no phase-separated droplets were observed in YTHDF2-mut cells.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed enhanced proliferation at the time points of 48 h(t=3.654,P=0.006)and 72 h(t=5.458,P<0.001)after 22 weeks of sodium arsenite treatment.The scratch healing rate of YTHDF2-wt cells was increased at the 8th(t=12.137,P<0.001)and 22th(t=4.484,P=0.011)weeks of sodium arsenite treatment.The number of colonies formed by YTHDF2-wt cells was higher at the 4th(t=3.365,P=0.027),8th(t=5.580,P=0.005),and 22th(t=3.328,P=0.029)weeks of sodium arsenite treatment.Compared with YTHDF2-mut cells,YTHDF2-wt cells showed down-regulated protein(t=-3.119,P=0.036)and mRNA(t=4.051,P=0.015) levels of PTEN after 22 weeks of sodium arsenite treatment.Immunofluorescence results showed that after 4 weeks of sodium arsenite treatment,YTHDF2 LLPS droplets in YTHDF2-wt cells were localized to stress granules,translation-related membrane-less organelles.Conclusions During sodium arsenite-induced malignant transformation of skin cells,YTHDF2 undergoes LLPS and localizes to stress granules,translation-related membrane-less organelles.YTHDF2 LLPS participates in sodium arsenite-induced malignant transformation of skin cells by down-regulating the mRNA level of the key tumor suppressor PTEN.
Arsenites/toxicity* ; Sodium Compounds/toxicity* ; Humans ; Cell Transformation, Neoplastic/drug effects* ; PTEN Phosphohydrolase/metabolism* ; Cell Proliferation ; Skin/cytology* ; RNA-Binding Proteins ; Skin Neoplasms/chemically induced* ; Cell Line

Sodium nitrite (SN, NaNO2) is a water-soluble, white-yellow crystalline powder with broad applications in food preservation, automotive maintenance, and animal control. It is a strong oxidizing agent that can oxidize hemoglobin iron (Fe) to its oxidized state, leading to methemoglobin formation. An increasing trend of suicide cases by SN ingestion has been reported globally following its popularization in online suicide forums providing detailed instructions of its use solely or as part of a “suicide kit.” We report a case of a 21-year-old male who was found continuously vomiting, with blood per orem and cyanosis of the mouth and digits. Within minutes of the onset of symptoms, the patient lost consciousness and was pronounced dead on arrival at the nearest emergency room. Autopsy findings showed lip erosions, hemorrhage, and perioral and peripheral cyanosis. Internal examination showed characteristic bright red muscle discoloration, dark brown arterial blood, red-brown congested visceral organs, and hyperemic esophageal and gastric mucosa. Methemoglobin studies from sampled arterial blood showed elevated levels (17.5%). Further investigation of the decedent’s belongings, social media posts, and recent online purchases reinforced the intentional sodium nitrite ingestion. While there are plenty of reported SN poisoning in suicide cases internationally, limited reports have been published locally. Death by SN poisoning is preventable with Methylene blue. The role of forensic pathologists through autopsy may be the last chance to detect such cases. The lack of systemic death investigation, experts, and local laboratories to reliably detect the signs of SN poisoning may have affected the low detection rate of cases locally. Further reporting of cases can raise the awareness of medical professionals that is fundamental to the ultimate saving of lives.

Sodium ; Wastewater ; Potassium ; Diet ; Blood Pressure ; China ; Sodium, Dietary ; Sodium Chloride, Dietary

BACKGROUND

Caustic ingestion is a major public health problem worldwide [1]. It imposes huge economic burden in terms of medical cost to poorly resourced health system of developing countries [2]. Household cleaning products, such as sodium hypochlorite (NaOCI), are the most common cause of caustic exposure [3]. NaOCI ingestion consistently ranks second in caustic ingestion cases in Northern Mindanao Medical Center (NMMC) based on toxicology census from 2015 to 2018. The aim of this study is to determine the epidemiologic profile, clinical findings and outcome of admitted patients who ingested NaOCI.

This a single-center descriptive, cross-sectional study of 40 cases of sodium hypochlorite ingestion admitted at NMMC from January 2015 to December 2018.

There were a total of 17 males and 23 females. Majority of patients were 0-5 years of age (46.5%; mean age of 2), followed by age range of 18-64 years old (40.0%; mean age of 35). Twenty-nine cases (72. 5%) cases of NaOCI ingestion were accidental and the remaining 11 (27.5%) were non-accidental. The non-accidental cases belong to the 12-17 (mean age 15.3) and 18-64 (mean age 31) years old age groups at 33.3% and 66.7%, respectively, with prevalence in females at 81.8%. Non-accidental cases increase with age, and among females. Majority of all ingested less than 50 ml of NaOCI. Two non-accidental cases (18.2%) ingested more than 100 ml of NaOCI were observed to have more than 2 signs and symptoms. Majority of patients presented with vomiting. Greater portion of non- accidental cases complained of abdominal or epigastric pain (54.5% vs 10%), oropharyngeal erythema (9.1 % vs 6.9), and odynophagia (45.5% vs 0). None of the patients had serious signs and symptoms. All patients were discharged improved and without sequelae.

Most NaOCI cases were accidental especially in children. Non-accidental cases increase significantly with age, with most cases found among adolescents and young adults, with higher prevalence among females. Majority of patients only ingested less than 50 ml, and that ingestion of 100 ml or more of NaOCI is associated with more than 2 signs and symptoms. The most predominant symptom is vomiting. Greater portion of non-accidental cases complained of abdominal or epigastric pain and odynophagia. None of the patients exhibit severe signs and symptoms. This study showed that all 40 cases of sodium hypochlorite ingestion did not have sequelae upon discharge.

The aim of this study was to conduct in vivo experiments using laser speckle contrast imaging (LSCI) technology to investigate the effects of high salt diet on renal vascular reactivity in mice. LSCI is a technology for monitoring blood flow based on the laser speckle principle. It has been widely used to detect microcirculatory functions in tissues such as the skin and brain. The kidneys are located behind the peritoneum, and their position is easily affected by the movement of abdominal organs. Measuring renal microcirculation in a living individual is difficult. The present study used a self-made kidney cup to isolate the kidney and fix its position relatively, and then applied LSCI technology to explore the effect of high salt diet (8% Na⁺) on renal vascular reactivity in male and female mice in vivo. The results showed that a short-term high salt diet (1 week) did not affect the systolic blood pressure of the tail artery, while significantly increased glomerular filtration rate (GFR) and renal blood flow (RBF). Compared with the normal salt diet group, the high salt diet group showed a significant decrease in the ratio of post-occlusive reactive hyperemia (PORH) in male mice, while there was no significant change in the PORH ratio in female mice. These results suggest that, although a short-term high salt diet does not cause changes in blood pressure, it has already affected renal vascular reactivity and has gender differences in its effects. Furthermore, the present study provides a basis for renal microcirculation assessment using LSCI in vivo.
Animals ; Mice ; Male ; Female ; Kidney/blood supply* ; Renal Circulation/physiology* ; Laser Speckle Contrast Imaging ; Sodium Chloride, Dietary/adverse effects* ; Microcirculation/physiology* ; Mice, Inbred C57BL

OBJECTIVE: To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis. METHODS: Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis. RESULTS: After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor β 1 (TGF- β 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- β 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05). CONCLUSION Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β 1/Smad signaling pathway.
Rats ; Animals ; Stroke Volume ; Sodium Chloride ; Rats, Inbred Dahl ; Ventricular Function, Left ; Heart Failure ; Transforming Growth Factor beta1/metabolism* ; Hypertension ; Fibrosis ; RNA, Messenger

Objective: JWH133, a cannabinoid type 2 receptor agonist, was tested for its ability to protect mice from bleomycin-induced pulmonary fibrosis. Methods: By using a random number generator, 24 C57BL/6J male mice were randomly divided into the control group, model group, JWH133 intervention group, and JWH133+a cannabinoid type-2 receptor antagonist (AM630) inhibitor group, with 6 mice in each group. A mouse pulmonary fibrosis model was established by tracheal instillation of bleomycin (5 mg/kg). Starting from the first day after modeling, the control group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution, and the model group mice were intraperitoneally injected with 0.1 ml of 0.9% sodium chloride solution. The JWH133 intervention group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg, dissolved in physiological saline), and the JWH133+AM630 antagonistic group mice were intraperitoneally injected with 0.1 ml of JWH133 (2.5 mg/kg) and AM630 (2.5 mg/kg). After 28 days, all mice were killed; the lung tissue was obtained, pathological changes were observed, and alveolar inflammation scores and Ashcroft scores were calculated. The content of type Ⅰ collagen in the lung tissue of the four groups of mice was measured using immunohistochemistry. The levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in the serum of the four groups of mice were measured using enzyme-linked immunosorbent assay (ELISA), and the content of hydroxyproline (HYP) in the lung tissue of the four groups of mice was measured. Western blotting was used to measure the protein expression levels of type Ⅲ collagen, α-smooth muscle actin (α-SMA), extracellular signal regulated kinase (ERK1/2), phosphorylated P-ERK1/2 (P-ERK1/2), and phosphorylated ribosome S6 kinase type 1 (P-p90RSK) in the lung tissue of mice in the four groups. Real-time quantitative polymerase chain reaction was used to measure the expression levels of collagen Ⅰ, collagen Ⅲ, and α-SMA mRNA in the lung tissue of the four groups of mice. Results: Compared with the control group, the pathological changes in the lung tissue of the model group mice worsened, with an increase in alveolar inflammation score (3.833±0.408 vs. 0.833±0.408, P<0.05), an increase in Ashcroft score (7.333±0.516 vs. 2.000±0.633, P<0.05), an increase in type Ⅰ collagen absorbance value (0.065±0.008 vs. 0.018±0.006, P<0.05), an increase in inflammatory cell infiltration, and an increase in hydroxyproline levels [(1.551±0.051) μg/mg vs. (0.974±0.060) μg/mg, P<0.05]. Compared with the model group, the JWH133 intervention group showed reduced pathological changes in lung tissue, decreased alveolar inflammation score (1.833±0.408, P<0.05), decreased Ashcroft score (4.167±0.753, P<0.05), decreased type Ⅰ collagen absorbance value (0.032±0.004, P<0.05), reduced inflammatory cell infiltration, and decreased hydroxyproline levels [(1.148±0.055) μg/mg, P<0.05]. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group showed more severe pathological changes in the lung tissue of mice, increased alveolar inflammation score and Ashcroft score, increased type Ⅰ collagen absorbance value, increased inflammatory cell infiltration, and increased hydroxyproline levels. Compared with the control group, the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK proteins in the lung tissue of the model group mice increased, while the expression of type Ⅰ collagen, type Ⅲ collagen, and α-SMA mRNA increased. Compared with the model group, the protein expression of α-SMA (relative expression 0.60±0.17 vs. 1.34±0.19, P<0.05), type Ⅲ collagen (relative expression 0.52±0.09 vs. 1.35±0.14, P<0.05), P-ERK1/2 (relative expression 0.32±0.11 vs. 1.14±0.14, P<0.05), and P-p90RSK (relative expression 0.43±0.14 vs. 1.15±0.07, P<0.05) decreased in the JWH133 intervention group. The type Ⅰ collagen mRNA (2.190±0.362 vs. 5.078±0.792, P<0.05), type Ⅲ collagen mRNA (1.750±0.290 vs. 4.935±0.456, P<0.05), and α-SMA mRNA (1.588±0.060 vs. 5.192±0.506, P<0.05) decreased. Compared with the JWH133 intervention group, the JWH133+AM630 antagonistic group increased the expression of α-SMA, type Ⅲ collagen, P-ERK1/2, and P-p90RSK protein in the lung tissue of mice, and increased the expression of type Ⅲ collagen and α-SMA mRNA. Conclusion: In mice with bleomycin-induced pulmonary fibrosis, the cannabinoid type-2 receptor agonist JWH133 inhibited inflammation and improved extracellular matrix deposition, which alleviated lung fibrosis. The underlying mechanism of action may be related to the activation of the ERK1/2-RSK1 signaling pathway.
Mice ; Male ; Animals ; Pulmonary Fibrosis/pathology* ; Cannabinoid Receptor Agonists/metabolism* ; Collagen Type I/pharmacology* ; Collagen Type III/pharmacology* ; Hydroxyproline/pharmacology* ; Sodium Chloride/metabolism* ; Mice, Inbred C57BL ; Lung/pathology* ; Cannabinoids/adverse effects* ; Bleomycin/metabolism* ; Collagen/metabolism* ; Inflammation/pathology* ; RNA, Messenger/metabolism*

OBJECTIVE: This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children. METHODS: School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables. RESULTS: Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status. CONCLUSION Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.
Humans ; Child ; Nutritional Status ; Cross-Sectional Studies ; Iodine ; Sodium Chloride, Dietary/analysis* ; China ; Water