High Levels Of Potassium Research Articles

Clinical Outcome and Risk Factors for Emergency Department Adult Patients with Thoracic Empyema after Video-Assisted Thoracic Surgical Procedure.

Background: Empyema is a purulent infection of the pleural cavity that is most relevant to parapneumonia effusion. Video-assisted thoracoscopic surgery (VATS) is an option for stage 2 (fibrinopurulent) and stage 3 (organizational). Surgeons may see critically ill patients with pleural empyema who present to the emergency department (ED). The purpose of this work is to investigate the outcomes of ED adult patients with thoracic empyema undergoing a thoracoscopic surgical procedure and to identify possible risk factors for death. Methods: We reviewed retrospectively the clinical characteristics and treatment outcomes of patients with thoracic empyema who received this diagnosis at our center from January 2012 to June 2014. Patients <20 years old were excluded from this study. The prognostic values of age, sex, comorbidities, clinical presentations, location, stage, and laboratory examinations were evaluated. Uni-variable analysis and multi-variable modeling were performed to determine significant risk factors for post-operative death. Results: Seventeen of 160 patients died post-operatively. Two groups (survivors and non-survivors) significantly differed in age (p = 0.013), sex (p = 0.026), comorbidity (p = 0.017), cough (p = 0.024), chest pain (p = 0.016), serum hemoglobin (p = 0.001), and potassium (p = 0.004) levels. Further logistic regression analysis showed statistically significant differences in age, hemoglobin levels, and potassium levels. Conclusion: Among the ED patients with thoracic empyema, older age, lower hemoglobin levels, and higher potassium levels are associated with post-operative death after VATS. These findings underline the importance of careful peri-operative treatment in older patients with signs of empyema when they present to the ED.

Combined effects of cropping system and harvest date determine quality and nutritional value of pomegranate fruits (Punica granatum L. cv. Gabsi)

The oasis environment, where Tunisian pomegranates are cultivated simultaneously with several crops, was shown to fulfill ecological functions. Few studies related to the effects of environmental factors on pomegranate pre-harvest quality have been carried out, and even less have focused on the interaction between oasis environment and harvest date. This study aims to evaluate the physico-chemical and nutritional properties of pomegranate fruits cultivated under and outside oasis in order to determine the most accurate harvest indices and harvesting date in relation with cropping system. Results revealed that oasis environment was more favorable to produce large sized-fruits with high aril yield and high juice content compared to full sun conditions. Oasis pomegranates exhibited high total anthocyanin content, high hydrophilic antioxidant activity, high level of magnesium, potassium and manganese content. The visual colour of fruits and arils as well as TSS/TA ratio were found the most reliable maturity indices for taking harvest decision of pomegranate fruits. A better red coloration of fruit and arils associated with a balance between sugar content and acidity as well as high nutritional value (high mineral contents particularly Mg, K, Mn, high flavonoid and anthocyanin contents) of pomegranates harvested from different orchards at mid-october (D3) indicated their optimal use at this stage. Nevertheless, the full sun exposed fruits harvested at beginning of October (D2), characterized by pink/pink reddish colour, high TSS content and (TSS/TA) ratio and high calcium content, were considered as matured (commercial maturity) and would be ready for harvesting. Final fruit quality depends on both environmental factors and maturity stage. Based on the identified indices, Gabsi pomegranate harvesting could be started in regular full sun exposed plantations, then in orchards under date palm trees and at least one week later in traditional oases.

Biophysical Modeling Suggests Optimal Drug Combinations for Improving the Efficacy of GABA Agonists after Traumatic Brain Injuries.

Traumatic brain injuries (TBI) lead to dramatic changes in the surviving brain tissue. Altered ion concentrations, coupled with changes in the expression of membrane-spanning proteins, create a post-TBI brain state that can lead to further neuronal loss caused by secondary excitotoxicity. Several GABA receptor agonists have been tested in the search for neuroprotection immediately after an injury, with paradoxical results. These drugs not only fail to offer neuroprotection, but can also slow down functional recovery after TBI. Here, using computational modeling, we provide a biophysical hypothesis to explain these observations. We show that the accumulation of intracellular chloride ions caused by a transient upregulation of Na+-K+-2Cl- (NKCC1) co-transporters as observed following TBI, causes GABA receptor agonists to lead to excitation and depolarization block, rather than the expected hyperpolarization. The likelihood of prolonged, excitotoxic depolarization block is further exacerbated by the extremely high levels of extracellular potassium seen after TBI. Our modeling results predict that the neuroprotective efficacy of GABA receptor agonists can be substantially enhanced when they are combined with NKCC1 co-transporter inhibitors. This suggests a rational, biophysically principled method for identifying drug combinations for neuroprotection after TBI.

Chemical and Antioxidant Analysis of &amp;lt;i&amp;gt;Spirulinaplatensis&amp;lt;/i&amp;gt; Products Available in Some Local Market

A comparative study was conducted to evaluate quality of Spirulinaplatensis products like powder and tablets that were manufactured by different companies in Bangladesh. The powder form was collected from Bangladesh Spirulina Company Ltd. and was named as SP-1. On the other hand, the tablets were collected from Eureka International, Life Line International and Evergreen Enterprise’s and were as named as SP-2, SP-3 and SP-4, respectively. The parameters investigated in this study were moisture content, ash content, acid insoluble and acid soluble ash content, crude fat content, nitrogen and protein content. Additionally, the amount of different solvent extracts, phytochemical screening, determination of total phenolic and flavonoids contents and antioxidant activity (DPPH radical scavenging activity), reducing power assay and total antioxidant activity and elemental analysis were also investigated. DPPH radical scavenging activity, reducing power assay and total antioxidant activity of all samples extract of four varieties showed significant/good/moderate activity, especially methanol and water extracts showed significant activity. All the four varieties of Spirulinaplatensis possessed good reducing power. Results of elemental analysis of four verities of Spirulinaplatensis showed significant difference. Analysis of mineral composition revealed the presence of sufficient amount of minerals such as sodium, potassium, iron and zinc. High levels of potassium were observed in all the samples. Heavy metals were also analyzed like lead, copper, chromium etc. Some of the samples were found to have contained lead in significant amounts. The reducing powers of the methanol and water extracts of four different samples (Spirulinaplatensis) were found to be significant in comparison with the standard ascorbic acid. The total antioxidant capacities of the methanol and water extracts of four different samples (Spirulinaplatensis) were found to be moderately significant in comparison with the standard ascorbic acid. From the result of this study, it is observed that different samples of Spirulinaplatensis contained different amount of physicochemical, chemical and antioxidant properties. However, among of the four products, SP-3 was found to have the best quality.

Effect of Different Level of Potassium on the Yield of White Jute (&amp;lt;i&amp;gt;Corchorus capsularis L.&amp;lt;/i&amp;gt;) Fibre in Coastal Region of Bangladesh

To examine the effect of variety and different level of potassium (K) on yield of jute, an experiment was conducted at the Agronomy Field Laboratory, Patuakhali Science and Technology University, Dumki, Patuakhali from May to September 2016 using three variety viz. C-2197, C-3069 and C-3473. There are four levels of K viz. 0, 35, 45 and 55 kg ha-1. The land was fertilized as per treatment specifications from muriate of potash along with recommended doses of urea, TSP, gypsum and zinc sulphate. The experiment was laid out in randomized complete block design (RCBD) with three replications. The variety O-3069 had significant influence on number of internodes per plant (64.20), plant diameter (21.15mm), fiber weight per plant (25.92g), fiber yield (5.18t ha-1), stick weight per plant (64.75g) and stick yield (12.94t ha-1). The highest results of plant height (3.81m) and green weight with leaf (4.04kg/10 plant) were obtain from C-3473 and green weight without leaf (3.54 kg/10 plant) were obtained from C-2197. Among the different potassium levels 55kg K ha-1 had significant influence on number of internodes per plant (70.13), plant diameter (22.60mm), green weight with leaves (4.43kg/10 plant) and green weight without leaves (3.91kg/10 plant), fiber weight per plant (27.93g), fiber yield (5.59t ha-1), stick weight per plant (69.60g) and stick yield (13.90t ha-1). The highest plant height (4.13m) were obtained from 35 kg K ha-1. The variety O-3069 with 55kg K ha-1 had significant influence on plant diameter (24.00mm), fiber weight per plant (31g), fiber yield (6.2t ha-1), stick weight per plant (77.53g) and stick yield (15.50t ha-1). The highest results of plant height (4.30m), number of internodes per plant (73), green weight with leaf (4.85kg/10 plant) and green weight without leaf (4.25kg/10 plant were obtain from C-3473 with 55kg K ha-1. The results of the present experiment showed that the C-3069 was the best among the varieties. On the other hand, 55kg k ha-1 was proved to be better than any other lower and higher levels of potassium. Therefore, it can be inferred that jute can produce the highest fibre yield from a combination of variety C-3069 with 55kg k ha-1 in field under the coastal region of Bangladesh.

High serum potassium level is associated with successful electrical cardioversion for new-onset atrial fibrillation in the intensive care unit: A retrospective observational study.

Electrical cardioversion (ECV) is a potentially life-saving treatment for haemodynamically unstable new-onset atrial fibrillation (AF); however, its efficacy is unsatisfactory. We aimed to elucidate the factors associated with successful ECV and prognosis in patients with AF. This retrospective observational study was conducted in two mixed intensive care units (ICUs) in a university hospital. Patients with new-onset AF who received ECV in the ICU were enrolled. We defined an ECV session as consecutive shocks within 15 minutes. The success of ECV was evaluated five minutes after the session. We analysed the factors associated with successful ECV and ICU mortality. Eighty-five AF patients who received ECV were included. ECV was successful in 41 (48%) patients, and 11 patients (13%) maintained sinus rhythm until ICU discharge. A serum potassium level ≥3.8 mol/L was independently associated with successful ECV in multivariate analysis (odds ratio (OR), 3.13; 95% confidence interval (CI), 1.07-9.11; p = 0.04). Maintenance of sinus rhythm until ICU discharge was significantly associated with ICU survival (OR 9.35; 95% CI 1.02-85.78, p = 0.048). ECV was successful in 48% of patients with new-onset AF developed in the ICU. A serum potassium level ≥3.8 mol/L was independently associated with successful ECV, and sinus rhythm maintained until ICU discharge was independently associated with ICU survival. These results suggested that maintaining a high serum potassium level may be important when considering the effectiveness of ECV for AF in the ICU.

Relationship Between Taurine Intake and Cardiometabolic Risk Markers in Korean Elderly.

Taurine can suppress the creation of lipid hydroperoxide and decrease the level of total cholesterol and triglyceride in the blood. This study aimed to analyze the relationship between biochemical indicators associated with cardiometabolic disease and taurine intake in elderly people. Subjects of this study were those participated in the Korea National Health and Nutrition Examination Survey (KNHANES) 2016, aged over 75years old. Data of dietary intake were collected through 24-h dietary recall method, and for nutrient analysis, the taurine intake was divided into quadrants. Mean values of taurine intake were 237.8 ± 17.5mg/day in men and 157.5 ± 12.4mg/day in women. Both men and women in the quadrants with the higher level of taurine intake appeared to show high intake levels of energy, protein, fat, total cholesterol, calcium, phosphorus, sodium, potassium, riboflavin, and niacin. As a result of relationship analysis between taurine intake and cardiometabolic risk markers (total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, blood pressure, blood glucose, and atherogenic index), taurine intake showed a significantly negative relation with AI in men but showed a positive relation in women with DBP.

Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent.

Succinylcholine (Sch) is the only depolarizing neuromuscular blocking agent widely used for rapid sequence induction in emergency rooms. Unfortunately, a variety of (sometimes lethal) adverse effects, such as hyperkalemia and cardiac arrest, are associated with its use, and currently there are no specific antidotes to reverse Sch or to treat these side-effects.Methods: The binding behaviors of Sch and several synthetic receptors, including cucurbit[7]uril, sulfo-calix[4]arene and water-soluble carboxylatopillar[6]arene (WP[6]), were first investigated. With a mouse model, a leathal dose of Sch was selected for evaluation of the antidotal effects of these synthetic receptors on Sch induced mortality. The antidotal effects of a selected synthetic receptor, WP[6], on Sch induced cardiac arrhythmias, hyperkalemia, rhabdomyolysis and paralysis were subsequently evaluated with rat and mouse models. The reversal mechanism was also investigated at a cellular level.Results: All of these macrocyclic molecules exhibited relatively high binding affinities with Sch in vitro. In a Sch-overdosed mouse model, immediate injection of these synthetic receptors right after Sch administration increased the overall survival rate, with WP[6] standing out with the most effective antidotal effects. In addition, administration of WP[6] also reversed the paralysis induced by Sch in a mouse model. Moreover, infusion of WP[6] to Sch-overdosed rats reduced the incidence of cardiac arrhythmia, inhibited the otherwise abnormally high serum potassium levels, and relieved the muscular damage. At the cellular level, WP[6] reversed the Sch induced depolarization and reduced the efflux of intracellular potassium.Conclusion: Synthetic receptors, particularly WP[6], exhibited high binding affinities towards Sch, and presented a significant potential as supramolecular therapeutics to treat the various side effects of Sch by specifically sequestering Sch in vivo.

Production of functional spreadable processed cheese using Chlorella vulgaris.

Chlorella vulgaris alga is one of the most important additives for enhancing the nutritional content of conventional foods, hence positively affecting human health. This alga is known as a rich source of protein, fatty acids, fiber, essential vitamins and minerals. Also, it contains antioxidants, omega 3, antivi- ral and anticancer properties. The aim of this research is increasing the nutritional and potential therapeutic value of processed cheese by using Chlorella vulgaris alga, taking advantage of its high nutritional and health value. The ingredients in the processed cheese blends were mature cheddar cheese, Ras cheese, butter, skimmed milk powder, Emulsifying salts (K-2394, S9s & S4), Chlorella vulgaris (in freeze- dried and slurry forms). Chemical, rheological and sensory evaluation properties were evaluated in processed cheese analogue (PCA) treatments when fresh and after three months of cold storage at 5&ndash;7&deg;C. PCA treat- ments were enriched with 2%, 4% and 6% dried Chlorella vulgaris powder in the cheese blends and 4% Chlorella vulgaris slurry. The incorporation of alga into processed cheese led to an increase in their functional characteristics. The results of sensory evaluation of PCA samples demonstrated that 2% of alga addition was the best treat- ment, followed by 4%, but that the level of 6% was unacceptable to consumers. The studied alga enhanced the cheese analog with the high levels of selenium, zinc, iron, magnesium and potassium. Antioxidant activity in the cheese enhanced with Chlorella vulgaris was higher than the control sample. To improve some proper- ties of PCA, other emulsifying salts (S9S and S4) were tested and the alga was added in the form of slurry with value of 4% into the cheese blend. Both S9S and S4 emulsifying salts were good and the S4 was the best for oiling off and meltability. Also, when using the slurry of Chlorella vulgaris, the granular texture of the cheese analog completely disappeared. The results showed that the alga indeed increased nutrition values and health benefits to the processed cheese, making it a substantial functional food. Therefore, we recommend supporting the manu- facture of the processed cheese analogue with the addition of 2% Chlorella vulgaris alga in soft powder form and 4% Chlorella vulgaris alga in slurry form at the end of the processing.

Extent of Groundwater Contamination Due to Leachate Migration Adjacent to Unlined Landfill Site of Delhi

The leachate and groundwater samples were collected from the 2 km radius of Ghazipur landfill site. The high levels of EC, TDS, Chloride, Nitrate, Sodium, Potassium, BOD, and COD were observed in the leachate and groundwater samples. In leachate, metal concentrations were found in the order as – Fe > Zn > Cu > Pb > Ni > Cr > Cd. In groundwater, Zn, Ni, and Cu ranged as 0–0.386 mg/l, 0–0.013 mg/l, and 0–0.027 mg/l, respectively whereas Cd, Cr, and Pb were found in trace amount. The study clearly indicates that the percolation of leachate from the landfill site results in the contamination of groundwater of the surrounding area.

Prevalence, Characteristics and Predictive Factors of Microalbuminuria in Resistant Systemic Arterial Hypertension

The present cross-sectional observational study was made in family medicine offices of Timi� County, Romania. The aim of the study was to investigate the prevalence of urinary microalbumin excretion (MAU) in resistant systemic arterial hypertension (RH), to analyze patients� biochemical and clinical characteristics, and the predictive factors for MAU. From a total number of 347 patients, MAU was detected in 76 cases (21.9%). The microalbuminuria positive patients were older, with significant higher office systolic blood pressure (BP) (155 � 13.50 vs 148 � 12.40 mmHg, p [ 0.0001) and diastolic blood pressure (94 � 12.20 vs 88 � 14.6 mmHg, p = 0.0013), higher prevalence of left ventricular hypertrophy, diabetes mellitus, obesity, ischemic and peripheral arterial disease. MAU positive patients presented statistical significant differences in biochemical data concerning: fasting plasma glucose (FPG) (118.80 � 32.02 vs 108.01 � 26.01 mg/dL, p = 0.003), impaired glucose tolerance (IGT) (10.52 % vs 4.94 %), glycated hemoglobin (HbA1c) (6.56 � 0.98% vs 5.96 � 0.91%, p [ 0.001), reduced estimated glomerular filtration rate (eGFR) (56.10 � 15.4 vs 69.30 � 17.5 ml/min/1.73m2, p [ 0.001) and higher potassium levels (4.71 � 0.43 vs 4.59 � 0.44 mg/dL, p = 0.0378). No significant differences were noticed regarding LDL- and HDL-cholesterol, triglycerides, uric acid and serum creatinine. In a logistic multivariate analysis independent predictors for MAU were: systolic BP (odds ratio, OR = 1.024, 95% confidence interval, CI:1.011-1.039, p [ 0.001), HbA1c (OR = 1.324, 95% CI: 1.078-1.724, p = 0.008) and eGFR (OR = 0.989, 95% CI: 0.977-0.999, p = 0.01). Our findings suggest that an important part of RH patients have microalbuminuria and highlight the importance of controlling its predictors, in order to improve patients� outcome.

Outcome and prognostic factors of patients treated in the intensive care unit for carbon monoxide poisoning

Carbon monoxide (CO), a colorless and odorless gas, is one of the common causes of poisoning-related deaths worldwide. CO poisoning can result in hypoxic brain damage and death, but intensive care can improve the likely outcome for critically ill patients. However, there is a paucity of clinical data regarding the prognostic factors and association between organ dysfunction and clinical outcome of patients treated for CO poisoning in the intensive care unit (ICU). We performed a retrospective study of patients admitted to a university affiliated hospital ICU between July 2001 and December 2010 following CO poisoning. Outcomes were survival to ICU discharge and to hospital discharge. Seven hundred and eighty-seven patients were admitted to the university hospital following CO poisoning, of which 140 (17.8%) were admitted to the hospital ICU. The overall mortality rate of the patients admitted to the ICU was 14.3% (20/140). Univariate analysis indicated that non-surviving patients with CO poisoning were more likely to have initial blood carboxyhemoglobin (COHb) level>30%, shock, acute respiratory failure, Acute Physiology and Chronic Health Evaluation II (APACHE II) score≥25, Glasgow coma scale (GCS) score of 3, acute renal failure, dysfunction or failure of more than 3 organs, low blood pH, low HCO3- level, high potassium level, and high glucose level. They were also more likely to have not received hyperbaric oxygen (HBO) intervention. Multivariate logistical regression analysis indicated that the mortality rate of patients treated in the ICU for CO poisoning was higher if their initial APACHE II score was ≥25, GCS was 3, and more than 3 organs were dysfunctional. Moreover, HBO intervention in ICU significantly decreased patients' risk of mortality due to CO poisoning. In conclusion, we observed that APACHE II score >25, GCS 3, and dysfunction of more than 3 organ systems on admission to emergency department was associated with a significant mortality risk in patients treated in the ICU for CO poisoning. Moreover, HBO therapy could reduce the risk of mortality in patients with CO poisoning in ICU.

Incidence and Prognosis of Acute Renal Failure in Patients with Severe Sepsis and Septic Shock

Background: Sepsis is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. Acute kidney injury (AKI), previously called acute renal failure (ARF) is an abrupt loss of kidney function, Generally it occurs because of damage to the kidney tissue caused by decreased kidney blood flow (Kidney ischemia) from any cause. AKI may lead to a number of complications, including metabolic acidosis, high potassium levels, uremia, changes in body fluid balance, and effects on other organ systems, including death. Aim: The aim of the study is to show the incidence and prognosis of acute renal failure in patients with sepsis and septic shock. Patients and methods: This prospective randomized study was conducted on patients who were admitted to ICU in Ain Shams University Hospitals. Forty patients were included in this study and an informed written consent was obtained from patients and/or relatives. All patients were adult, more than 18 years old, admitted to ICU suffering from severe sepsis or had septic shock for monitoring, management and follow up to their condition in period of six months. All patients were more than 18 years old that were critically ill either in severe sepsis or had septic shock. We excluded patients less than 18 years old, patient or relatives who refused to be included in this study, and if he/she has a history of previous kidney troubles or dysfunction. All patients were subjected to assessment of the demographic data of the patient, causes and site of infection, pathogenic bacteria as declared by different cultures, APACHE 2 score on admission, all patients were managed as declared by ICU, protocol for septic patients, hemodynamic monitoring was done daily, routine lab investigation daily, coagulation profile had to be done on days 0, 3, 7 of admission, SOFA score on days 0, 3, 7 of admission, renal functions include blood urea and creatinine clearance test had to be done daily, any deterioration of renal function was reported, and if the patient was in need for renal replacement therapy or dialysis, this would be reported. Results: Forty patients were included in this study, their ages with a mean of 58.37 ± 15.66 years. 23 patients (57.5%) were males and 17 patients (42.5%) were females. The most frequent risk factors were hypertension (62.5%) followed by diabetes (52.5%). The incidence of AKI was 60% of patients and the need for renal replacement therapy (RRT) was 9 (22.5%). Outcome of admitted patients in ICU was 23 (57.5%) survived patients and 17 (42.5%) non-survived patients. The study showed that there were no statistical significant differences between AKI and Non-AKI patients except for; gender (male), BMI, gram –ve bacterial infection, creatinine, BUN, creatinine clearance, history of ACE administration, use of vasopressors, APACHE II score at admission and mortality were statistically significant (p < 0.05). Conclusion: The incidence of AKI was 60% of patients in our study. The development of septic AKI adversely affected clinical outcomes. Moreover, the severity of AKI was associated with increased short-term mortality as observed in ICU patients. The study showed that there were no statistical significant differences between AKI and Non-AKI patients except for; gender (male), BMI, gram –ve bacterial infection, creatinine, BUN, creatinine clearance, history of ACE administration, use of vasopressors, APACHE II score at admission and mortality were statistically significant (p < 0.05).

Cardiac Excitation Waves under Strong Hyperkalemia Condition

Normal blood levels of potassium are critical for maintaining normal heart electrical rhythm. Both low blood potassium levels (hypokalemia) and high blood potassium levels (hyperkalemia) can lead to abnormal heart rhythms. The aim of the work presented is to study the effect of potassium concentration on the excitation wave in the cardiac tissue. Results have been obtained both in the experimental model, which is a monolayer of neonatal rat cardiomyocytes, and in the modified Korhonen computer model, designed for ventricular rat neonatal cardiomyocytes. The existence of non-sodium excitation waves under a strong hyperkalemia (more than 10 mM K + in the extracellular environment) in the cardiomyocyte monolayer has been found and has also be confirmed by inactivation of sodium channels with a specific channel blocker.

NEXT GENERATION SEQUENCING AND EXPERIMENTAL MYOLOGY: P.374Identification of gene mutations in patients with primary periodic paralysis using targeted next-generation sequencing

Primary periodic paralysis comprises rare skeletal ion channelopathies characterized by recurrent quadriplegia typically associated with high or low serum potassium levels. We developed a gene panel that includes 10 ion channel-related genes and 245 muscular dystrophy- and myopathy-related genes and used this panel to diagnose 60 patients with primary periodic paralysis and identify the disease-causing or risk-associated gene mutations. The average sequencing depth using this panel was 488.11 ×, and the average coverage was 99.45%. Mutations in 5 genes were discovered in 40 patients (66.67%). Variants in SCN4A, KCNJ2 and CACNA1S genes accounted for 92.5% of the patients with a genetic diagnosis. SCN4A (NM_000334) mutations accounted for the majority in this primary PP cohort (47.5%). We identified 10 SCN4A variants including 5 reported mutations (c.2014C>T p.Arg672Cys, c.2024G>A p.Arg675Gln, c.2111C>T p.Thr704Met, c.4352G>T p.Arg1451Leu, and c.4774A>G p.Met1592Val) and 5 novel mutations (c.107_109del p.Glu36del, c.121C>T p.Arg41Trp, c.718G>A p.Val240Met, c.3868T>C p.Phe1290Leu and c.5293G>A p.Ala1765Thr). Among them, c.2024G>A p.Arg675Gln was identified in 8 patients from 6 families as a hotspot. KCNJ2 is the second most common genetic cause.We identified 9 reported variants (c.199C>T p.Arg67Trp, c.211G>A p.Asp71Asn, c.556C>A p.Pro186Thr, c.566G>T p.Arg189Ser, c.644G>A p.Gly215Asp, c.652C>T p.Arg218Trp, c. 899G>A p.Gly300Asp, c.919A>G p.Met307Val, and c.921G>C p.Met307Ile) in a total of 14 patients. Moreover, we identified 4 likely pathogenic variants (c.614T>A p.Phe205Tyr, c.1583G>A p.Arg528His, c.2965G>A p.Glu989Lys and c.3716G>A p.Arg1239His) in CACNA1S gene (NM_000069). Two RYR1 variants (p.Glu2764Lys and p.Ala4143Val) were identified in this cohort, together with one reported OPA1 variant (p.Ala357Thr) which is previously responsible for optic atrophy related phenotypes. Using targeted NGS, we achieved a diagnostic success rate of 66.67% in a cohort of primary PP patients. We expanded the spectrum of genotypes of primary PP and clinical phenotypes of known myopathy-related genes. We'd like to attribute this diagnostic rate to the inclusive strategy of screening for other causal factors of hypokalaemic muscle weakness and performing accurate clinical examinations and history inquiries prior to interpreting the NGS results.

Abstract IA25: Identification of essential genes for cancer immunotherapy

Abstract Cancer immunotherapies can trigger dramatic responses in a subset of patients, but many patients with common types of cancer (e.g., breast, ovary, pancreatic, brain and colon) do not experience significant benefit from immunotherapy. The priority now must be determining what makes some cancers resist the immune system, even after treatments designed to fortify the body’s natural antitumor capabilities. Understanding the mechanisms of immune resistance and tumor escape could help enhance tumor immunotherapy. Virtually every cancer contains mutations within protein-encoding genes. These mutations can create targets that can be recognized by immune cells, but mutations may also impair immune recognition and enable immune escape. We have previously observed that cancer cells can escape immune recognition via loss of heterozygosity (LOH) and mutations in β2 microglobulin, which are common in human tumors. These historical findings are important because current cancer immunotherapies mostly rely on T cells, which are adept at recognizing cells in which genetic disruptions have generated aberrant proteins. Anti-CTLA-4 or PD1/PDL1 work in large part by releasing natural checkpoints that constrain T-cell activity. Chimeric antigen receptor T-cell therapies (CAR-T), generated by genetically altering a patient’s T cells, can trigger long-lasting remissions in some patients with blood cancers, but have not yet been definitively found to be effective in solid cancers. These therapies build on a deep understanding of T-cell biology gleaned from decades of basic research. To obtain a more complete, whole-genome visualization of why immunotherapies sometimes fail, we explored the factors that influence tumor cells’ vulnerability to T-cell killing. Using a library of 123,000 guide RNAs, we employed a CRISPR-Cas9 system to systematically eliminate the function of every protein-encoding gene. Surprisingly, this genome-wide screen identified dozens of new genes that potentially influence tumor cells’ susceptibility to T-cell attack. When these genes were knocked-out, tumor cells were significantly more likely to survive and continue to multiply after exposure to T cells that we had genetically engineered to recognize tumor-associated antigens. Many of the genes identified in our screen were previously known to be involved in T cell-tumor cell interactions, including those mediating antigen processing and presentation and responses to cytokines. However, dozens of unique “hits” from the CRISPR screen had not previously been linked to T cells’ ability to eliminate their targets. Loss-of-function mutations in these novel resistance genes were found at high rates in patients for whom immunotherapies failed. Given the diverse gene set revealed by our CRISPR screens and the complexity of the tumor microenvironment, which can include high levels of immunosuppressive potassium, it seems unlikely that a single “fix” will enhance immunotherapy. Instead, we must develop a new category of drugs that circumvent these escape mechanisms. We hope our findings will serve as a blueprint to guide comprehensive studies of what makes some tumors resist T-cell control. Ultimately, novel combination immunotherapies based on individual gene mutations may enable the expansion of curative immunotherapy. Selected

Morpho-anatomical, physiological and biochemical adaptive responses to saline water of Bougainvillea spectabilis Willd. trained to different canopy shapes

Bougainvillea is widely used as potential ornamental shrub in revegetation and landscaping projects as well as in urban landscape design in Mediterranean areas characterized by saline and sodic soils. The current research aimed at elucidating the morphological, physiological and biochemical changes occurring in Bougainvillea spectabilis ‘Alexandra’ grown under salt stress conditions (1 mM [S1, electrical conductivity EC = 2.0 dS m−1] non-salt control, 40 mM [S40, EC = 6.5 dS m−1] and 80 mM [S80, EC = 11.0 dS m−1] NaCl). The response of plants trained to two canopy shapes (globe [GSh] and pyramid [PSh]) has been compared in order to unravel possible adaptive mechanisms, combining morpho-functional traits at different levels, to cope with saline water. PSh plants under moderate saline water (40 mM NaCl) showed higher leaf dry weight, leaf number and area as well as higher number of flowers per plant than those observed in GSh Bougainvillea plants. Saline water-triggered leaf anatomical changes were also harmonized to physiological adjustments in both canopy shapes in such a way to counteract the reduction in transpiration due to stomatal limitations by adopting traits improving CO2 diffusion in the mesophyll and investing more resources in the assimilatory tissue (e.g. increase in intercellular spaces and incidence of palisade parenchyma over the total mesophyll thickness). Bougainvillea plants enact many-sided strategies to acclimate to S80 salinity by harmonizing several mechanisms including sodium and chloride inclusion in leaves and their compartmentalization in vacuoles, retention of high levels of potassium in the cytosol to osmotically balance the cytoplasm and other organelles within the vacuole, modulation of leaf functional anatomical traits, in addition to a C2 Kranz mechanism of photosynthesis which allow plants to successfully cope with stress.

Nutritional potential of leaves and tubers of crem (Tropaeolum pentaphyllum Lam.)

ABSTRACT Objective To determine the centesimal composition of minerals, fatty acids and vitamin C of leaves and tubers of crem, and to discuss the nutritional potential of the T. pentaphyllum species. Methods The centesimal composition of protein, lipid, fiber, ash and carbohydrate was determined by gravimetric analysis. Mineral composition was determined by optical emission spectrometry. Vitamin C was determined by dinitrophenylhydrazine method. Fatty acids were determined by gas chromatography. The percentage of recommended dietary intake of leaves and tubers of crem was calculated for each nutrient. Results A high content of fibrous fraction (63.07g/100g), potassium (4.55g/100g), magnesium (553.64mg/100g) and sulfur (480.79mg/100g) was observed in the chemical composition of leaves. In tubers, a high carbohydrate content was observed, with 62.60g/100g of starch and 3.43g/100g of fiber, as well as high potassium (0.58g/100g), sulfur (447.14g/100), calcium (205.54g/100g) and phosphorus (530.07g/100g) levels. The vitamin C content of tubers was 78.43mg/100g and the linoleic acid content was 0.455g/100g. The intake of 100g of crem leaves may contribute with 65% of the recommended dietary intake of sulfur. The intake of 100g of crem tuber may contribute with 106% of the recommended dietary intake of sulfur and 21% of the recommended dietary intake of Vitamin C. Conclusion The chemical composition of crem (Tropaeolum pentaphyllum Lam.) tubers and leaves demonstrated an important contribution of nutrients, mainly sulfur, vitamin C and linoleic acid in its tubers, indicating a high nutritional potential of this species.

Anthropogenic sources of potassium in surface water: The case study of the Bystrzyca river catchment, Poland

A three-year river monitoring was carried out in the Bystrzyca River catchment (Poland) dominated by arable areas and wastewater treatment plants. The concentrations of potassium (K) – “a neglected nutrient” – in fresh waters were determined. Analysis of variance (ANOVA) and principal component analysis (PCA) showed spatial and seasonal variability in potassium concentrations. The highest potassium levels were observed in sites located directly below the outlet of the sewage treatment plant of Lublin. The impact of smaller sewage treatment plants on the water quality of the Bystrzyca River was low. Contents of K+ in waters situated in areas experiencing crop and animal production were significantly lower in comparison to ‘sewage’ points. There was a differentiation of correlations between concentrations of K and NH4-N, NO3-N and PO4-P depending on the source of pollution. The potassium levels in river waters usually decreased in early spring.

Abnormal serum potassium levels and 6-month all-cause mortality in patients co-treated with antipsychotic and diuretic drugs – A Danish register-based cohort study

Psychiatric patients have excess mortality compared to the general population, and several potential mechanisms may explain this increased risk. This study examined the relationship between serum potassium levels and risk of all-cause mortality in patients co-treated with antipsychotic and diuretic drugs. Using a register-based cohort design, we identified patients between 1995 and 2012 who received a combination of an antipsychotic and a diuretic drug and who further had a serum potassium measurement within 90 days. During the study period, we included the most frequently redeemed antipsychotic drugs with regard to the propensity of corrected QT (QTc) prolongation: zuclopenthixol (unknown/mild), flupentixol (mild), levomepromazine (moderate), and quetiapine (moderate/severe). Patients co-treated with antidepressant drugs, lithium, and other antipsychotic drugs were excluded. Outcome was 6-month all-cause mortality, estimated with multivariable Cox regression. Patients were divided into seven serum potassium levels using restricted cubic splines (reference: 4.2–4.4 mmol/L) and stratified according to the included antipsychotic drugs. Of 6729 patients (median age: 74.0 years; women: 65.3%), 10.8% had hypokalemia and 4.9% had hyperkalemia. Hyperkalemia (>5.0 mmol/L, HR 2.82 [95% CI 2.25–3.54]), hypokalemia (<3.5 mmol/L, HR 1.59 [95% CI 1.29–1.95]), and high normal potassium levels (4.5–4.7 mmol/L, HR 1.44 [95% CI 1.19–1.75]; 4.8–5.0 mmol/L, HR 1.60 [95% CI 1.26–2.04]) were associated with an increased risk of 6-month all-cause mortality. This risk was independent of antipsychotic drugs (interaction: P = 0.06). Our findings imply that excess mortality in patients co-treated with antipsychotic and diuretic drugs is related to serum potassium levels and independent of antipsychotic drugs.