Mild Recovery Research Articles

Stabilized chlorophyll-based food colorants from spinach: Kinetics of a tailored enzymatic extraction.

An organic solvent-free method based on limited dosing options (biocatalyst and zinc chloride) for the quick and mild recovery of chlorophyll (Chl) from spinach has been proposed. This tailored, custom-made protocol has been designed to produce stable green natural colorants. The kinetics of pigment extraction turned out to be a very useful tool to identify the proper conditions, in terms of biocatalyst dose (0.10-50U/g), extraction time (1-48h), and ZnCl2 amount (50-300ppm), both for enhancing the recovery yield and preserving the green color. Considering the extraction kinetics, the recovery yield, and the colorimetric data, the suitable conditions to produce stable green and food-grade colorants are 0.10U/g of enzyme, 3h, and 150ppm of ZnCl2 at 25°C. The extraction yield of Chl (4863µg/U) was about 51% greater than control, with a higher extraction rate constant (5.43×10-4g/(µgmin)). Considering the impact of ZnCl2 amount on Chl, its protective action resulted to be more noticeable toward Chl a: at 150ppm, an increased amount of about 2.5 and 1.5 times was found for Chl a and Chl b, respectively, in comparison to the reference (0ppm ZnCl2). PRACTICAL APPLICATION: This research demonstrates how a suitable kinetic approach helps to provide a tailored protocol, customized for the vegetable matrix, to produce stable green natural colorants from spinach. Lowering enzyme dosage and ZnCl2 amount during the extraction of chlorophyll at low temperature is crucial for its potential use as a colorant in food industry, providing high economic values through saving time and environmental protection.

Magnetic Nanoparticle-Based Microfluidic Platform for Automated Enrichment of High-Purity Extracellular Vesicles.

Extracellular vesicles (EVs) are available in various biological fluids and have highly heterogeneous sizes, origins, contents, and functions. Rapid enrichment of high-purity EVs remains crucial for enhancing research on EVs in tumors. In this work, we present a magnetic nanoparticle-based microfluidic platform (ExoCPR) for on-chip isolation, purification, and mild recovery of EVs from cell culture supernatant and plasma within 29 min. The ExoCPR chip integrates bubble-driven micromixers and immiscible filtration assisted by surface tension (IFAST) technology. The bubble-driven micromixer enhances the mixing between immunomagnetic beads and EVs, eliminating the need for manual pipetting or off-chip oscillatory incubation. The high-purity EVs were obtained after passing through the immiscible phase interface where hydrophilic or hydrophobic impurities nonspecifically bound to SIMI were removed. The ExoCPR chip had a capture efficiency of 75.8% and a release efficiency of 62.7% for model EVs. We also demonstrated the powerful performance of the ExoCPR in isolating EVs from biological samples (>90% purity). This chip was further employed in clinical plasma samples and showed that the number of GPC3-positive EVs isolated from hepatocellular carcinoma patients was significantly higher than that of healthy individuals. This ExoCPR chip may provide a promising tool for EV-based liquid biopsy and other fundamental research.

Defibrillated Lignocellulose Recovery Guided by Plant Chemistry and Anatomy – A Pioneering Study with Lupinus angustifolius

AbstractThe strive toward sustainability increases the demand for bio‐based material production, forcing expansion of the biorefinery feedstock supply from forest wood to non‐woody materials such as agricultural residues. As a model organism for legume crops, the aptness of agricultural lupins as a lignocellulose feedstock is investigated. Principle chemical analysis combined with optotracing, in which the fluorescent tracer molecule Carbotrace 680 generates a visual map of the native tissues’ lignocellulose anatomy at sub‐cellular resolution, enables informed design of a mild recovery process. A streamlined conversion approach is then designed, yielding lignin‐containing microfibrillated cellulose. By monitoring defibrillation and delignification throughout the extraction process, the use of optotracing for non‐destructive fiber analytics at unprecedented details across all hierarchical structures of lignocellulosic materials is demonstrated. This crop valorization is a prime illustration of a holistic use of lupin biomass, with seeds serving as plant‐based food sources, and other parts as sources for lignocellulose‐based materials, thereby expanding both the biorefinery concept and feedstock supply.

Insuficiencia respiratoria en paciente con dengue en la unidad de cuidados intensivos. Reporte de un caso

The dengue epidemic currently affecting the Lambayeque department has set a historic record in terms of the number of diagnosed dengue patients compared to previous years. Additionally, numerous complications such as hemorrhages, multiorgan failure, and acute respiratory distress syndrome (ARDS) have been observed. This is why the case of a 60-year-old patient with sensory impairment and ARDS as the main complication is presented. Initially, she was treated at a private clinic and later referred to the Lambayeque Regional Hospital, where she was immediately assisted in the emergency department. After a few days, she showed mild recovery. However, after 10 days of symptoms with warning signs, she was admitted to the intensive care unit of the hospital for ARDS management.

Ameliorative effects of palm oil on sniper induced toxicity on the cerebral cortex of adult male Wistar rats

Introduction: Sniper insecticide is a highly toxic, water soluble, synthetic organophosphate belonging to the DDVP (2, 2 — dichlorovinyl dimethylphosphate) compound family of chemicals. It’s wide spread indiscriminate indoor usage and more recently, an effective instrument for suicide related mortality which has been a source of great concern. Red palm oil, on the other hand, is an edible vegetable oil from the fleshy pulp of the oil palm that contains antioxidants; carotenoids that is responsible for its color (pigmentation) and Vitamin E that support brain health. This palm oil is consumed widely, used as an antidote in Nigeria and so is used for various ingested poisons. Aim: This study is aimed at investigating the ameliorative effects of palm oil on sniper induced toxicity on the cerebral cortex. Materials and methods: Sixteen adult male Wistar rats were randomly assigned to 4 groups (n = 4 per group). Group A was the Control, while Group B was administered just sniper (5 mg/kg), Group C was administered 2 ml of Red oil and Group D received 5 mg/kg of sniper + 2 ml of red oil. At the end of the experiment, the rats were sacrificed, their brains extracted and fixed in 10% formal saline for routine histological analysis. Results: There was significant increase in the body weight of Groups A, B, C and D. The relative organ weight of Wistar rats showed an insignificant decrease in the relative brain weight of Group B compared to the Control. Groups C and D also had a relative decrease in comparison to the control. The cerebral cortex reveals neuronal damage and proliferation of glial cells in the sniper-induced group and the mild recovery of neuronal cells in the rats treated with sniper and palm oil. Conclusion: The results from this study shows that there was a significant reduction in organ weight in Group B [Sniper only] when compared to the control group. When palm oil was administered, there was mild recovery of neuronal cells. This shows the ameliorative effects/ impact of Palm Oil in Neurotoxicity.

Glucagon and exenatide improve contractile recovery following ischaemia/reperfusion in the isolated perfused rat heart.

The inotropic effects of glucagon have been recognized for many years, but it has remained unclear whether glucagon signaling is beneficial to cardiac function. We evaluated the effects of glucagon alone and in combination with the glucagon-like peptide 1 (GLP-1) receptor agonist exenatide in the isolated perfused rat heart. The isolated perfused rat heart was used to investigate the initial inotropic and chronotropic effects of glucagon and exenatide during aerobic perfusion, and recovery of contractile function following ischaemia/reperfusion. Glucagon, but not exenatide, elicited an acute chronotropic and inotropic response during aerobic perfusion of the rat heart. Compared with control, glucagon improved recovery of left ventricular developed pressure (LVDP) by 33% (p< 0.05) and rate-pressure product (RPP) by 66% (p< 0.001) following ischaemia/reperfusion and amplified the mild recovery enhancement elicited by exenatide in a dose-dependent manner. Glucagon shows inotropic properties in the isolated perfused rat heart and improves contractile recovery following ischaemia/reperfusion, both alone and when co-administered with a GLP-1 receptor agonist. Glucagon and exenatide, a GLP-1 receptor agonist, combine to stimulate greater recovery of postischaemic contractile function in the Langendorff heart. Glucagon was inotropic and chronotropic, yet this initial effect decreased over time and did not account for the increased contractility observed postischaemia/reperfusion.

Chemical Composition, Antitumor Potential, and Impact on Redox Homeostasis of the Essential Oils of Orlaya grandiflora from Two Climate Localities

It is well known that abiotic components can affect biosynthetic pathways in the production of certain volatile compounds. The aim of this study was to compare the chemical composition of essential oils obtained from Orlaya grandiflora (L.) Hoffm. collected from two localities in Serbia (continental climate, OG1) and Montenegro (Mediterranean climate, OG2) and to assess their antitumor potential on the human colon cancer HCT-116 and breast cancer MDA-MB-231 cell lines. EOs obtained by hydrodistillation were analyzed using GC-MS and GC-FID methods. The results indicate considerable differences in the chemical compositions of the two samples. Although in both samples the main class of volatiles observed was sesquiterpenes (47.5% for OG1 and 70.1% for OG2), the OG1 sample was characterized by a high amount of monoterpene hydrocarbons (29.3%), and sesquiterpene germacrene D (29.5%) as the most abundant compound. On the other hand, the OG2 sample contained a high quantity of oxygenated sesquiterpenes (20.6%), and β-elemene (22.7%) was the major constituent. The possible antitumor mechanisms of these EOs in the HCT-116 and MDA-MB-231 cell lines were examined by means of cell viability, apoptosis, redox potential, and migratory capacity. The antiviability potential appeared to be dose dependent, since the results showed that both EOs decreased the viability of the tested cells. Stronger antitumor effects were shown in MDA-MB-231 cells after short-term treatment, especially at the highest applied concentration, where the percentage of viability was reduced by over 40%. All tested concentrations of EOs exhibited proapoptotic activity and elevated activity of caspase-3 in a dose- and time-dependent manner. The results also showed decreased concentrations of superoxide anion radical in the treated cells, which indicates their significant antioxidative role. Long-term treatments showed mild recovery effects on cell viability in both cell lines, probably caused by the balancing of redox homeostasis. Elevated levels of nitrites indicate high levels of nitric oxide (NO) production and suggest its higher bioavailability due to the antioxidative environment. The tested EOs also induced a drop in migratory capacity, especially after short-time treatments. Taken together, these results suggest considerable antitumor activity of both EOs, which could have potential therapeutic applications.

The Effect of Mediterranean Diet Compliance on COVID-19 Symptoms and Disease Severity

The aim of the research is to investigate the relationship between the adherence to a Mediterranean type of diet, which is an anti-inflammatory diet, and the degree of severity and symptoms of the disease in patients with COVID-19 infection. In the study, a short questionnaire form containing questions about demographic information, disease severity, and what symptoms they experienced was given to individuals who had previously had COVID-19 infection. The adaptation of individuals to the Mediterranean diet (MD) was evaluated with the Mediterranean Diet Adherence Screener (MEDAS). SPSS software program was used to analyze the effect of the MD on COVID-19 severity and symptoms. A total of 715 people, including 283 (39.6%) men and 432 (60.4%) women, were included in the study. It was determined that 33.7% (241/715) of the individuals had MD compliance, while 66.3% (474/715) did not have MD compliance. It was observed that 77.8% (556/715) of the individuals participating in the study had a mild recovery from the COVID-19 infection process. It was observed that thin and obese individuals had more difficulty recovering (p&lt;0.05). The top 5 most common symptoms in COVID-19 patients were found to be as follows: fatigue-weakness (87%), low back-joint pain (76.4%), headache (70.5%), olfactory disorder (66%), and taste disorder (61%), respectively. No significant difference was found between adherence to a Mediterranean-type diet and COVID-19 severity and symptoms (p&gt;0.05). In conclusion, no significant relationship was found between adherence to the MD and the severity of the COVID-19 infection. However, considering the effects of the Mediterranean-type diet, which is an anti-inflammatory diet, on obesity, it is thought that adherence to this diet will have a positive effect on decreasing the severity of COVID-19 transmission indirectly, if not directly.

Amisulpride-induced late-onset rabbit syndrome: Case report and literature review

IntroductionAmisulpride is an atypical antipsychotic. Rabbit syndrome(RS) may be seen after antipsychotics use a few days or long‐term application. RS occurs after more frequent typical antipsychotics and also in rare cases atypical antipsychotics.Its characterized by the involuntary rhythmic movements of the lips however involves no tongue movements.ObjectivesCase report and reflection on its etiologyMethodsCase report and literature reviewResultsA 28-year-old female with a diagnosis of schizophrenia applied with the complaints and symptoms of withdrawal, do not want to leave the house, physical anergy and avolition that started after stopped taking her medications. She was admitted to the psychiatry service and amisulpride treatment was started and was gradually increased to 800 mg/day. After 30 days of hospitalization, the patient was discharged with mild recovery. 14 days after the discharge, because of the abnormal involuntary movements in mouth, the patient applied. In clinical examination without tounge involvement, rhythmic motions were observed in the lips and jaw.Neurological examination, labrotory tests and cranial screening were all normal. She was evaluated by a private psychiatrist and was diagnosed with RS. Amisulpride treatment changed to olanzapine treatment with 15 mg/day. After two months, RS spontaneously regressed.ConclusionsThe resolution of the involuntary movements following discontinuation of amisulpride in our case, supported the diagnosis of RS. Although the mechanism by which RS emerges as a side‐effect of amisulpride is not fully understood, the drug’s high affinity for and selective binding to dopaminergic D2 and D3 receptors are thought to be responsible for this involuntary motion disorder.DisclosureNo significant relationships.

Paraneoplastic cerebellar degeneration: A rare paraneoplastic syndrome

Paraneoplastic syndrome are rare disorders associated with cancers. Among then paraneoplastic cerebellar degeneration is classical PCS, presents acutely and sub acutely with walking incoordination, slurring of voice. Anti YO anti bodies are strongly associated with this PCS. Presence of anti YO antibody shows poor prognosis, and mild recovery with immunosuppressants. Treatment is not very promising in severely affected patient.

Free-living gait does not differentiate chronic mTBI patients compared to healthy controls

BackgroundPhysical function remains a crucial component of mild traumatic brain injury (mTBI) assessment and recovery. Traditional approaches to assess mTBI lack sensitivity to detect subtle deficits post-injury, which can impact a patient’s quality of life, daily function and can lead to chronic issues. Inertial measurement units (IMU) provide an opportunity for objective assessment of physical function and can be used in any environment. A single waist worn IMU has the potential to provide broad/macro quantity characteristics to estimate gait mobility, as well as more high-resolution micro spatial or temporal gait characteristics (herein, we refer to these as measures of quality). Our recent work showed that quantity measures of mobility were less sensitive than measures of turning quality when comparing the free-living physical function of chronic mTBI patients and healthy controls. However, no studies have examined whether measures of gait quality in free-living conditions can differentiate chronic mTBI patients and healthy controls. This study aimed to determine whether measures of free-living gait quality can differentiate chronic mTBI patients from controls.MethodsThirty-two patients with chronic self-reported balance symptoms after mTBI (age: 40.88 ± 11.78 years, median days post-injury: 440.68 days) and 23 healthy controls (age: 48.56 ± 22.56 years) were assessed for ~ 7 days using a single IMU at the waist on a belt. Free-living gait quality metrics were evaluated for chronic mTBI patients and controls using multi-variate analysis. Receiver operating characteristics (ROC) and Area Under the Curve (AUC) analysis were used to determine outcome sensitivity to chronic mTBI.ResultsFree-living gait quality metrics were not different between chronic mTBI patients and controls (all p > 0.05) whilst controlling for age and sex. ROC and AUC analysis showed stride length (0.63) was the most sensitive measure for differentiating chronic mTBI patients from controls.ConclusionsOur results show that gait quality metrics determined through a free-living assessment were not significantly different between chronic mTBI patients and controls. These results suggest that measures of free-living gait quality were not impaired in our chronic mTBI patients, and/or, that the metrics chosen were not sensitive enough to detect subtle impairments in our sample.

Is the behavior of sellers with expected gains and losses relevant to cycles in house prices?

We examine anchoring to the price paid at purchase during an important cycle in Connecticut, 2000–2017 which is similar to cycles in many other states. Our repeat sales model, which mitigates endogeneity and unobserved heterogeneity, provides robust estimates of negotiated price premiums (discounts) of sellers with expected losses (expected gains). Our model bridges from individual to aggregate price responses, and it supports new stylized facts about housing market cycles. Results suggest that anchoring was associated with reductions in observed changes in house prices during the boom (2004–2006) as sellers with gains dominate with their price discounts, and with reduced price declines during the bust (2007–2012) when the behavior of those with losses becomes important. Additional results making minimal model assumptions suggest that loss behavior is statistically significant and important at turning points, i.e., during the transition from a boom to a bust and vice versa. Double mean differences suggest that those with losses used the mild recovery as an opportunity to realize losses at reduced premiums after long delays.

Guillain-Barré Syndrome after Lung Transplantation in the Immediate Postoperative Period

A 58-year-old man, incapable of maintaining oxygen saturation with mechanical ventilation, was admitted to our hospital for veno-venous extracorporeal membrane oxygenation (ECMO) treatment. He was diagnosed with acute respiratory distress syndrome (ARDS) due to influenza A pneumonia. His condition stabilized with antibiotics and steroid administration, but weaning from ECMO failed due to post-infectious pulmonary sequelae. On day 84 after admission, he underwent bilateral lung transplantation. In the postoperative phase, he did not regain consciousness even after discontinuation of sedatives for 3 days. However, spontaneous pupillary reflex and eye movements were preserved, while communication and upper and lower limb movements were affected. The nerve conduction study was diagnostic of Guillain-Barre syndrome. He was managed with intravenous immunoglobulins and plasmapheresis. Mild recovery of the facial muscles was seen, but he died 24 days post-surgery due to progressive ARDS and sepsis.

Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury.

Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224N results in profound progressive functional deficit, memory impairment and brain pathology from 5h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier.

The mechanisms of lncRNA Tug1 in islet dysfunction in a mouse model of intrauterine growth retardation.

Taurine upregulated gene 1 (Tug1) is a novel lncRNA that participates in growth, and the abnormal expression of Tug1 related to mouse islet cell dysfunction. A recent study revealed that intrauterine growth retardation (IUGR) related to the pathogenesis of diabetes. Here, we aimed to explore the role and mechanism of Tug1 in IUGR-mediated islet dysfunction. We observed that newborn IUGR mice had lower body and pancreas weight and smaller islets than newborn control mice. After IUGR mice were given a normal diet, they showed catch-up growth and abnormal glucose tolerance; however, the pancreas/body weight ratio remained low. Blood glucose, serum insulin and related gene expression showed mild recovery after overexpression of Tug1 in IUGR mice. Furthermore, Tug1 was enriched in the nuclei of MIN6 cells. Using RIP and CHIP analyses we found that Tug1 could regulate Hes1 expression by binding to EZH2 to affect insulin synthesis in MIN6 cells. These findings indicate that lncRNA Tug1 could regulate the expression of Hes1 via EZH2-driven H3K27 methylation and affect insulin production. SIGNIFICANCE OF THE STUDY: This study suggests Tug1 as a novel biomarker, as it was shown to regulate β cell function and is worthy of further investigation due to its potential for diabetes treatment.

SAT-204 ACTH-Producing Pheochromocytoma, a Challenging Disease to Diagnose and Manage

Background: ACTH-producing pheochromocytomas (APP) are a rare cause of ectopic Cushing’s syndrome (CS), representing <6% of these cases. No guidelines exist on the management of these tumors. Clinical case: A 41-year-old woman presented to the ED with a 6-month history of newly-diagnosed T2DM and difficult-to-control hypertension. Three weeks prior to admission she developed fatigue, dyspnea on exertion, and generalized weakness particularly severe in the lower extremities (LE) limiting her ability to ambulate. She denied headaches, palpitations and diaphoresis. Initial vital signs included HR 111 beats/min and BP 217/112 mmHg. On physical exam she had classic findings of CS with severe LE weakness. Laboratory testing was consistent with ACTH-dependent CS (ACTH 463 pg/mL [0-45], cortisol 70.8 mcg/dL [3-23], potassium 2.7 mMol/L [3.1-5.1]). She failed both the low dose (1 mg) and high dose (8 mg) dexamethasone suppression tests. MRI of the pituitary gland ruled out a pituitary lesion. IPSS was not deemed necessary by Neurosurgery. CT abdomen showed a 4.2 cm right adrenal lesion and bilateral adrenal hyperplasia. This prompted workup for pheochromocytoma that revealed elevated plasma metanephrines (4.1 nMol/L, [<0.5]) and 24hr urine metanephrines (5329 mcg/day, [182-739]). A diagnosis of APP was entertained. Doxazosin 1 mg BID was added to her other antihypertensives with improvement in blood pressure. Ketoconazole 200 mg TID was started as a bridge for surgery. Patient underwent right unilateral adrenalectomy one month after initial presentation. ACTH and cortisol levels before surgery were 534 pg/mL and 87 mcg/dL, respectively, suggesting that ketoconazole was not effective. Both ACTH and cortisol levels decreased to 26 pg/mL and 14.4 mcg/dL, respectively, immediately after surgery. There was prompt subjective symptomatic improvement, including mild recovery of LE strength. Her blood pressure normalized and only spironolactone was continued. She was started on a prednisone taper. Pathology revealed a 4.2 pheochromocytoma and diffuse adrenocortical hyperplasia. Tumor cells stained positive for ACTH on immunohistochemistry. On follow up visit 2 months after surgery patient was feeling well and ambulating without difficulty. Labs were remarkable for normal plasma fractionated metanephrines, and A1c 5.1% on metformin alone (down from 4 medications on initial presentation). Conclusion: Diagnosis and management of APP can be challenging. Alpha-blockers should be started promptly. Definitive treatment with unilateral adrenalectomy is curative and has been recommended as the preferred approach.1 Ketoconazole may be used as bridge therapy for surgery, though some studies suggest its efficacy might be lower in ectopic CS.2 Response to other pharmacologic agents is largely unknown.

Functional Studies on Novel RET Mutations and Their Implications for Genetic Counseling for Hirschsprung Disease.

Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of ganglion cells in the gut. RET is considered to be the main susceptibility gene. In our previous screening of 83 HSCR patients, targeted exome sequencing identified nine rare variants of RET, most of which were new discoveries. Here, we performed in vitro arrays with functional studies to investigate their effects. Two variants (p.R77C and p.R67insL) were demonstrated to disrupt the glycosylation of RET and affect its subcellular localization. Three nonsense mutations (p.W85X, p.E252X, and p.Y263X) could not produce detectable RET full-length protein, and the other three mutations (p.R770X, p.Q860X, and p.V778Afs*1) were translated into truncated proteins of predicted sizes. One canonical splice acceptor site mutation (c.2802-2 A > G) was verified to affect gene regulation through aberrant splicing. In addition, we explored the effects of read-through reagents on RET nonsense mutations and showed that G418 significantly increased the full-length RET protein expression of p.Y263X in a dose-dependent manner, together with a mild recovery of p-ERK and p-STAT3. Our data provide a functional analysis of novel RET mutations and suggest that all of the rare variants detected from patients with clinically severe HSCR are indeed pathogenic. Thus, our findings have implications for proper genetic counseling.

Changes in nonlinear dynamic complexity measures of blood pressure during anesthesia for cardiac surgeries using cardio pulmonary bypass.

Nonlinear complexity measures computed from beat-to-beat arterial BP dynamics have shown associations with standard cardiac surgical risk indices. They reflect the physiological adaptability of a system and has been proposed as dynamical biomarkers of overall health status. We sought to determine the impact of anesthetic induction and cardiopulmonary bypass (CPB) upon the complexity measures computed from perioperative BP time series. In this prospective, observational study, 300 adult patients undergoing cardiac surgery were included. Perioperative period was divided as: (1) Preoperative (PreOp); (2) ORIS-induction to sternotomy; (3) ORSB- sternotomy to CPB; (4) ORposB-post CPB and within 30min before leaving OR and (5) postoperative phase (PostOp)-initial 30min in the cardiac surgical intensive care unit. BP waveforms for systolic (SAP), diastolic (DAP), mean arterial pressure (MAP) and pulse pressure (PP) were recorded, and their corresponding complexity index (MSE∑) was calculated. Significant decrease in MSE∑ from Preop to PostOp phases was observed for all BP time series. Maximum fall was seen during post anesthetic induction (ORIS) phase. Mild recovery during the subsequent phases was observed but they never reached the baseline values. In an exploratory analysis, preoperative MSE∑ showed a significant correlation with postoperative length of ICU stay. Blood pressure complexity varies at different time points and is not fixed for a given individual. Preoperative BP Complexity decreased significantly following anesthetic induction and did not recover to baseline until 30min after surgery. Prevention of this significant fall may offer restoration of MSE∑ throughout surgery. Furthermore, preoperative BP complexity needs to be explored as a predictor of major postoperative adverse events by itself or in addition with the current risk indices.

Thiamin Regresses the Anticancer Efficacy of Methotrexate in the Amelioration of Diethyl Nitrosamine-Induced Hepatocellular Carcinoma in Wistar Strain Rats

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and occurs frequently in patients with liver cirrhosis. HCC is the leading cause of cancer-related mortality around the globe.Aim: This study assessed the effects of thiamin in the anticancer activity of methotrexate (MTX) in diethyl nitrosamine (DEN) induced hepatocellular Carcinoma in Wistar strain male rats.Method: Fifty rats were randomly segregated in five groups with 10 rats in each group. HCC was induced by single intraperitoneal (i.p) dose of DEN (200 mg/kg) and HCC promoter phenobarbital was used in the basal diet (0.05%) for 5 days per week until the termination of the study in all the rats except for the normal control (NC) group. Disease control (DC) was given no treatment, while DM (DEN + MTX) and DT (DEN + thiamin) groups were given MTX (5 mg/kg, i.p per week for 16 weeks) and thiamin (25 mg/kg, orally, daily for 16 weeks), respectively. DMT (DEN + MTX + thiamin) group was given the combined dose of MTX and thiamin. Histopathological study was carried out to confirm the liver function tests such as α-feto protein (AFP), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TB), and total protein (TP) along with antioxidants vascular endothelial growth factor (VEGF), lipid per-oxidation (LPO), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT).Results: Results showed that liver biomarkers and antioxidants parameters were still abnormal in the DC group while DM group showed significant restoration, but DT group showed less significant normalization. DMT showed mild recovery of these parameters.Conclusion: The mechanism of action of MTX and thiamin is antiparallel to each other and hence their concomitant administration may lead to inefficient anticancer activity of MTX.

Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration.

BackgroundWe have previously reported that xeno-transplanted human ESC-derived retinas are able to mature in the immunodeficient retinal degeneration rodent models, similar to allo-transplantations using mouse iPSC-derived retina. The photoreceptors in the latter developed outer segments and formed synapses with host bipolar cells, driving light responses of host retinal ganglion cells. In view of clinical application, here we further confirmed the competency of human iPSC-derived retina (hiPSC-retina) to mature in the degenerated retinas of rat and monkey models.MethodsHuman iPSC-retinas were transplanted in rhodopsin mutant SD-Foxn1 Tg(S334ter)3LavRrrc nude rats and two monkeys with laser-induced photoreceptor degeneration. Graft maturation was studied by immunohistochemistry and its function was examined by multi-electrode array (MEA) recording in rat retinas and visually-guided saccade (VGS) in a monkey.FindingsA substantial amount of mature photoreceptors in hiPSC-retina graft survived well in the host retinas for at least 5 months (rat) to over 2 years (monkey). In 4 of 7 transplanted rat retinas, RGC light responses were detected at the grafted area. A mild recovery of light perception was also suggested by the VGS performance 1.5 years after transplantation in that monkey.InterpretationOur results support the competency of hiPSC-derived retinas to be clinically applied for transplantation therapy in retinal degeneration, although the light responses observed in the present models were not conclusively distinguishable from residual functions of degenerating host retinas. The functional analysis may be further elaborated using other models with more advanced retinal degeneration.