Spontaneous Opening Research Articles

Effects of desflurane and sevoflurane anesthesia on postoperative recovery after long-term tumor surgery

Objective: To analyze the effects of desflurane and sevoflurane anesthesia on postoperative recovery after long lasting tumor surgery. Methods: One hundred and sixty patients undergoing endoscopic radical esophagectomy and gastrectomy (80 cases of each surgical type) from November 2019 to March 2020 at Henan Cancer Hospital, were randomized into 4 groups(n=40): group CS (esophageal cancer+sevoflurane anesthesia), group DS (esophageal cancer+desflurane anesthesia),group CW (stomach cancer+sevoflurane anesthesia) and group DW (gastric cancer+desflurane anesthesia). General anesthesia was induced by intravenous agents in all four groups, which were maintained by inhaled anesthetic during the operation. The mean arterial pressure (MAP), heart rate (HR), and surplus pulse O(2) (SpO(2)) immediately before induction (T(1)), the moment of operation begin (T(2)), operation end (T(3)) and extubation (T(4)) were recorded. Also, the duration required for inhalation anesthetic alveolar concentration reaching 0.5 minimum alveolar concentration (MAC) during induction, the alveolar anesthetic concentration at the beginning of the operation, the duration required for XMAC (patients specific alveolar concentration) declining to 0.5 MAC on recovery period, and the duration of alveolar concentration of 0.5 MAC declining to 0.2 MAC were determined. Additionally, the durations of spontaneous breathing recovery, eyes opening, extubation and recovery of consciousness were recorded. Finally, restlessness score (RS) during recovery period was used to evaluate postoperative agitation. Results: Compared with group CS and group CW, no significant differences in MAP, HR, SpO(2) in group DS and group DW at T(1) to T(4) were found (all P>0.05). The durations required for inhalation anesthetic alveolar concentration reaching 0.5 MAC were (5.6±1.3), (5.8±2.1), (3.5±1.5) and (3.8±1.0) min in group CS, group CW, group DS and group DW, where the durations in group DS and group DW were significantly shorter than those in group CS and group CW (F=32.538, P<0.05). The durations of alveolar concentration of 0.5 MAC declining to 0.2 MAC were (6.4±2.2), (7.0±1.5), (4.2±2.2) and (4.1±1.5) min in group CS, group CW, group DS and group DW, and the durations in group DS and group DW were significantly shortened as compared with group CS and group CW (F=42.113, P<0.05). Compared with group CS and group CW, group DS and group DW required significantly shorter time for spontaneous breathing recovery, eye opening,extubation, and directional force recovery after operation (all P<0.05). Conclusions: Both desflurane and sevoflurane anesthesia can achieve satisfactory anesthesia depth during long lasting tumor surgery. Desflurane can shorten the recovery time and early extubation, and improve the quality of recovery.

Spinal epidural hematoma as a stroke mimic

PurposeSpinal epidural hematoma is a rare but important disease as it can be a stroke mimic. Our aim was to investigate the clinical characteristics of patients with an activated stroke code and spinal epidural hematoma. MethodsPatients with an activated stroke code were examined retrospectively. Patients with spinal epidural hematoma were evaluated with further neurological examinations and neuroimaging. ResultsOf 2866 patients with an activated stroke code, spinal epidural hematoma was detected in 5 (0.2%, 63–79 years, 2 men). In all 5 cases, hematoma was located in the unilateral dorsal region of the spinal canal and spread to 5–9 vertebral segments at the C1–T3 level. None of the patients had a medical history of head or neck injury, coagulopathy, or use of anti-thrombotic agents. All of the patients had occipital, neck, and/or back pain, and their hemiparesis occurred simultaneously or within 1 h after the onset of pain. Hyperalgesia ipsilateral to the hematoma was observed in 1 patient, hypoalgesia contralateral to the hematoma was observed in 1, and quadriparesis and bilateral hypoalgesia were observed in 1. The hematomas spontaneously decreased in size in 4 patients, and cervical laminectomy was performed in the other patient. In the 1860 patients with an activated stroke code and spontaneous eye opening, the sensitivity of pain as a predictor of spinal epidural hematoma was 100%, with a specificity of 88.7%, and positive predictive value of 2.3%. ConclusionPatients with spinal epidural hematoma could present with clinical characteristics mimicking ischemic stroke. Spinal epidural hematoma should be differentiated in patients treated under stroke code activation.

Evaluation of the perioperative effects of dexmedetomidine on tympanoplasty operations.

This randomized double-blind study aimed to evaluate the effects of dexmedetomidine on hemodynamic parameters and the quality of surgery and recovery criteria in tympanoplasty operations. A total of 75 patients 18-55years undergoing tympanoplasty, who were graded as American Society of Anesthesiologists physical status I-II, were randomly divided into three groups. Group 1 included patients receiving remifentanil alone, Group 2 included patients receiving dexmedetomidine + remifentanil and Group 3 included patients receiving dexmedetomidine + ½ remifentanil. Anesthesia was induced with propofol and cisatracurium. For maintenance of anesthesia, a mixture of 2-2.5% sevoflurane, 40-60% oxygen/air was used. The groups were compared in terms of hemodynamic parameters, surgical area, recovery criteria, modified Aldrete, pain scores, additional analgesic requirements and adverse effects. Mean arterial pressure and heart rate values of Group 1 were higher at the time of intubation, incision, spontaneous breathing and extubation compared to Group 2 and Group 3. Surgical field satisfaction was higher in Group 2 and Group 3 than Group 1. Spontaneous breathing, eye opening and verbal cooperation times were shorter in Group 3 compared to Group 2. Eye opening and verbal cooperation times were longer in Group 2 compared to Group 1. The 30-minute modified Aldrete scores was higher in Group 3 compared to Group 1. There was no difference between the groups in terms of postoperative pain and adverse effects. The use of dexmedetomidine during tympanoplasty operations may provide better hemodynamic control and surgical view, may provide faster recovery and may reduce remifentanil consumption.

An Option for Good Outcome of Intracerebral Hematoma

Abstract Background: Intracerebral hematoma affects about 2.5 per 10,000 people each year. The incidence is more in males and older people. The mortality rate is about 44% in the first month. 20% of cases has a good outcome. Symptoms can include headache, one-sided weakness, vomiting, seizures, decreased level of consciousness, and neck stiffness. Often symptoms get worse over time. In many cases bleeding occurs in the brain tissue and the ventricles at the same time. Many procedures and techniques have been introduced for the management of intracerebral hematoma and debate always exist about the management of sizable intracerebral hematomas especially if the conscious level isn't markedly affected. Aim of Study: To evaluate the role of early evacuation of sizable intracerebral hematomas even if the conscious level isn't markedly deteriorated. Method: This is a retrospective study of 30 cases of intracerebral hematoma operated in Kasr El-Aini Hospitals and Bani Suef University Hospitals by evacuation assisted by microscope with a Glasgow Coma Scale more than 10 in most cases with a sizable intracerebral haemorrhage more than 30cc in the volume. Results: This study results was 22 (73%) male patients and 8 (27%) was female patients. The age group was 4 patients (13%) under 30 years, 22 patients (73%) were from 30-45 years and 4 patients (13%) were more than 45 years old. The Glasgow Coma Scale (GCS) on admission was 14-15 in 4 patients (13%) patients, from 10-13 was 14 patients (46%), and from 9 and less was 12 patients (41%). 20 patients (67%) case was diabetics, 23 patients (46%) cases was hypertensive, 2 patients (7%) had chronic renal failure on regular dialysis, 1 patient (3%) case was pregnant. The GCS post-operative was 14-15 in 20 patients (70%), 10-13 in 5 patients (16%), and from 9 and less in 5 (24%) cases. The operation done was evacuation in all cases, decompressive craniectomy in 8 patients (26%), ventriculosubgaleal shunt done (VSG) in 3 patients (10%). The side of the hematoma was left sided in 7 patients (24%), right in 23 patients (76%). Good out come in 25 cases (83%), recollection in 3 (10%) cases, residual hematoma in 2 (6%) of the cases, re evacuation done in 1 patient (3%). Mortality were 4 patients.Conclusion: Sizable intracerebral hematoma (volume more than 30cc) in good Glasgow coma scale mostly obeying orders, spontaneous eye opening, and aphasic or not, to obtain a good outcome is to evacuate the hematoma not to wait for conservative management.

Efeitos do remifentanil sobre despertar de pacientes sedados com propofol para endoscopia digestiva alta: estudo clínico randomizado

Background and objectivesSedation for endoscopic procedures aims to provide high quality sedation, lower risks, short recovery time, superior recovery quality and absence of side effects, seeking high patient level of satisfaction. The goal of the study was to assess administration of remifentanil combined with propofol regarding the effects of the drug association during sedation and recovery for patients submitted to upper GI diagnostic endoscopy. MethodOne hundred and five patients were assessed, randomly divided into three groups of 35 patients. The Control Group was sedated with propofol alone. Study Group 1 was sedated with a fixed dose of 0.2 μg.kg‐1 remifentanil combined with propofol. Study Group 2 was sedated with 0.3 μg.kg‐1 remifentanil combined with propofol. We assessed the quality of sedation, hemodynamic parameters, incidence of significant hypoxemia, time for spontaneous eye opening, post‐anesthetic recovery time, quality of post‐anesthetic recovery, presence of side effects and patient satisfaction. ResultsStudy Group 1 showed better quality of sedation. The groups in which remifentanil was administered combined with propofol showed shorter eye‐opening time and shorter post‐anesthetic recovery time compared to the control group. The three groups presented hemodynamic changes at some of the moments assessed. The incidence of significant hypoxemia, the quality of post‐anesthetic recovery, the incidence of side effects and patient satisfaction were similar in the three groups. ConclusionsThe combination of propofol with remifentanil at a dose of 0.2 μg.kg‐1 was effective in improving the quality of sedation, and at doses of 0.2 μg.kg‐1 and 0.3 μg.kg‐1 reduced the time to spontaneous eye opening and post‐anesthetic recovery in comparison to sedation with propofol administered alone.

Effects of remifentanil on awakening of propofol sedated patients submitted to upper gastrointestinal endoscopy: a randomized clinical trial

Background and objectivesSedation for endoscopic procedures aims to provide high quality sedation, lower risks, short recovery time, superior recovery quality and absence of side effects, seeking high patient level of satisfaction. The goal of the study was to assess administration of remifentanil combined with propofol regarding the effects of the drug association during sedation and recovery for patients submitted to upper gastrointestinal diagnostic endoscopy. MethodOne hundred and five patients were assessed, randomly divided into three groups of 35 patients. The Control Group was sedated with propofol alone. Study Group 1 was sedated with a fixed dose of 0.2μg.kg−1 remifentanil combined with propofol. Study Group 2 was sedated with 0.3μg.kg−1 remifentanil combined with propofol. We assessed the quality of sedation, hemodynamic parameters, incidence of significant hypoxemia, time for spontaneous eye opening, post-anesthetic recovery time, quality of post-anesthetic recovery, presence of side effects and patient satisfaction. ResultsStudy Group 1 showed better quality of sedation. The groups in which remifentanil was administered combined with propofol showed shorter eye-opening time and shorter post-anesthetic recovery time compared to the control group. The three groups presented hemodynamic changes at some of the moments assessed. The incidence of significant hypoxemia, the quality of post-anesthetic recovery, the incidence of side effects and patient satisfaction were similar in the three groups. ConclusionsThe combination of propofol with remifentanil at a dose of 0.2μg.kg−1 was effective in improving the quality of sedation, and at doses of 0.2μg.kg−1 and 0.3μg.kg−1 reduced the time to spontaneous eye opening and post-anesthetic recovery in comparison to sedation with propofol administered alone.

A Novel Glycine Receptor Variant with Startle Disease Affects Syndapin I and Glycinergic Inhibition.

Glycine receptors (GlyRs) are the major mediators of fast synaptic inhibition in the adult human spinal cord and brainstem. Hereditary mutations to GlyRs can lead to the rare, but potentially fatal, neuromotor disorder hyperekplexia. Most mutations located in the large intracellular domain (TM3-4 loop) of the GlyRα1 impair surface expression levels of the receptors. The novel GLRA1 mutation P366L, located in the TM3-4 loop, showed normal surface expression but reduced chloride currents, and accelerated whole-cell desensitization observed in whole-cell recordings. At the single-channel level, we observed reduced unitary conductance accompanied by spontaneous opening events in the absence of extracellular glycine. Using peptide microarrays and tandem MS-based analysis methods, we show that the proline-rich stretch surrounding P366 mediates binding to syndapin I, an F-BAR domain protein involved in membrane remodeling. The disruption of the noncanonical Src homology 3 recognition motif by P366L reduces syndapin I binding. These data suggest that the GlyRα1 subunit interacts with intracellular binding partners and may therefore play a role in receptor trafficking or synaptic anchoring, a function thus far only ascribed to the GlyRβ subunit. Hence, the P366L GlyRα1 variant exhibits a unique set of properties that cumulatively affect GlyR functionality and thus might explain the neuropathological mechanism underlying hyperekplexia in the mutant carriers. P366L is the first dominant GLRA1 mutation identified within the GlyRα1 TM3-4 loop that affects GlyR physiology without altering protein expression at the whole-cell and surface levels.SIGNIFICANCE STATEMENT We show that the intracellular domain of the inhibitory glycine receptor α1 subunit contributes to trafficking and synaptic anchoring. A proline-rich stretch in this receptor domain forms a noncanonical recognition motif important for the interaction with syndapin I (PACSIN1). The disruption of this motif, as present in a human patient with hyperekplexia led to impaired syndapin I binding. Functional analysis revealed that the altered proline-rich stretch determines several functional physiological parameters of the ion channel (e.g., faster whole-cell desensitization) reduced unitary conductance and spontaneous opening events. Thus, the proline-rich stretch from the glycine receptor α1 subunit represents a multifunctional intracellular protein motif.

A rare case of spontaneous nephrocutaneous fistula

Acute and chronic pyelonephritis are known afflictions to the kidney in diabetics and in patients of abnormal urinary anatomy. And its presentation as a spontaneous sinus opening on the anterior abdominal wall is a rare phenomenon. We present one such rare case of a 71-year-old male with pus discharge from the anterior abdominal wall for 7 months. On investigating, it was found to be a nephrocutaneous fistula arising from the left non-functional kidney. This was dealt with left nephrectomy along with excision of the sinus tract. Though a very rare condition, a possibility of nephrocutaneous fistula must be kept when dealing with discharging sinus in lumbar region.

A Comparison of Different Remifentanil Effect-Site Concentrations to Allow for Early Extubation After Cardiac Surgery

Assess different remifentanil effect-site concentrations (Ce) for readiness for extubation time after cardiac surgery. Prospective, randomized, blinded, controlled study. Single university hospital. Seventy-three patients scheduled for cardiac surgery. After ethical approval, patients scheduled for cardiac surgery with target-controlled propofol infusion were randomly assigned to receive remifentanil effect-site concentrations (Ce) of 1, 2, or 3 ng/mL (n = 25, 25, and 23, respectively). The primary endpoint was readiness for extubation. Secondary outcomes were also recorded, including the cumulative doses and number of changes of propofol and remifentanil, hemodynamic variables, time to spontaneous eye opening and breathing, actual extubation, incidences of light anesthesia and myocardial ischemia, need for vasopressors and inotropes, and intensive care unit (ICU) and hospital stays. There was no difference in the time to readiness for extubation in any of the groups (0.1 ng/mL: 11.5 min (5-37); 0.2 ng/mL: 22 min (10-35); and 0.3 ng/mL: 21 min (10-49), p < 0.532); however, there was a significant difference among the 3 groups regarding the cumulative remifentanil doses (p < 0.001). Time to spontaneous eye opening and breathing, actual extubation, use of vasopressors and inotropes, incidences of light anesthesia and myocardial ischemia, and length of ICU and hospital stay were similar for all groups. Forty-six of the 73 patients were extubated on-table. Remifentanil Ce 1, 2, and 3 ng/mL produced comparative effects on time to extubation and hemodynamic responses to cardiac surgery. The 3 Ce resulted in immediate on-table extubation in 50% of patients.

Arthrocentesis and Sodium Hyaluronate Infiltration in Temporomandibular Disorders Treatment. Clinical and MRI Evaluation.

Arthrocentesis in temporomandibular joint disorders can be associated with the intra-articular infiltration of various drugs with the objective of increase treatment efficacy. The aim of this study was to evaluate the clinical indexes variation in patients affected by temporomandibular joint disorders treated with arthrocentesis and sodium hyaluronate (SH) injections. A total of 28 patients suffering from temporomandibular joint disorders underwent one cycle of five arthrocentesis and infiltrations of sodium hyaluronate. Spontaneous mouth opening improved from 36.3 ± 7.5 mm to 45.1 ± 1.9 mm at six months follow-up. A significant reduction in the pain at rest and during mastication mean values emerged at follow-up (p < 0.0001). The mean masticatory efficiency, evaluated through a visual analogic scale, showed improvement at the follow-up period, highlighted by the increase of mean value from a baseline of 3.1 ± 1.2 to a mean value of 8.5 ± 1.2 (p < 0.0001). The mean severity of the joint damage at baseline time was 2.4 ± 0.9 and decreased to 0.4 ± 0.3 at the end of the follow-up period. The decrease in values is confirmed by statistical test (p < 0.05). Our data show how arthrocentesis integrated with sodium hyaluronate infiltrations performed under local anesthesia is a valid method of treating temporomandibular joint disorders.

Dual Ca2+-Dependent Gates in Human Bestrophin1 Underlie Disease-Causing Mechanisms of Gain-Of-Function Mutations

Mutations of human BEST1, encoding a Ca2+-activated Cl- channel (hBest1), cause macular degenerative disorders. Best1 homolog structures reveal an evolutionarily conserved channel architecture highlighted by two landmark restrictions (named the “neck” and “aperture”, respectively) in the ion conducting pathway, suggesting a unique dual-switch gating mechanism, which, however, has not been characterized well. Using patch clamp and crystallography, we demonstrate that both the neck and aperture in hBest1 are Ca2+-dependent gates essential for preventing channel leakage resulting from Ca2+-independent, spontaneous gate opening. Importantly, three patient-derived mutations (D203A, I205T and Y236C) lead to Ca2+-independent leakage and elevated Ca2+-dependent anion currents due to enhanced opening of the gates. Moreover, we identify a network of residues critically involved in gate operation. Together, our results suggest an indispensable role of the neck and aperture of hBest1 for channel gating, and uncover disease-causing mechanisms of hBest1 gain-of-function mutations.

Dynamic Lateral Gate of BamA and TamA Regulated by POTRA Domains

The β-barrel assembly machinery (BAM) complex, which is responsible for the biogenesis of β-barrel membrane proteins, is thought to function through the lateral gating of its central component BamA. BamA contains 5 periplasmic polypeptide-transport-associated (POTRA) domains and a transmembrane β-barrel. However, how the lateral gate of the β-barrel is regulated and promotes the insertion of nascent substrate β-barrels remains unknown. To elucidate the mechanism, we carry out 36 μs of equilibrium simulations of BamA with and without POTRA domains from Escherichia coli, Salmonella enterica, Haemophilus ducreyi and Neisseria gonorrhoeae, together with BamA's homolog, TamA, of Escherichia coli in their native membranes. From these equilibrium simulations, we observe membrane thinning near the lateral gate in all of our systems, while unexpectedly TamA systems also have a thinner membrane at the opposite side of lateral gate. We also see occasional spontaneous lateral gate opening and sliding of the β-strands at the gate, indicating that the lateral gate is dynamic. Additionally, PMF calculations for lateral gate opening for all of our systems suggest that POTRA domains play an important role in regulating lateral gate opening.

Just Diverticulitis? A Very Rare Complication of a Very Common Disease!

Question: A 68-year-old woman presented to the emergency room of our hospital with reduced consciousness, fever (38.5°C/101.3°F) and abdominal pain. The initial clinical and neurologic examination showed the following findings: the patient was hemodynamically stable, in a confused state, discrete signs of meningism (positive Kernig’s sign), spontaneous movement of all extremities without localizing signs, mild increased tone of all extremities and spontaneous opening of eyes, which were equal and reactive to light.

Effects of propofol and sevoflurane on blood glucose, hemodynamics, and inflammatory factors of patients with type 2 diabetes mellitus and gastric cancer.

Effects of propofol and sevoflurane on blood glucose, hemodynamics, and inflammatory factors of patients with type 2 diabetes mellitus (T2DM) and gastric cancer (GC) were investigated. One hundred and ten patients with T2DM and GC, treated in The First Affiliated Hospital of Baotou Medical College (Baotou, China) from January 2017 to December 2018, were selected. Sixty patients anesthetized by propofol were included in the propofol group, whereas 50 patients anesthetized by sevoflurane were included in the sevoflurane group. The level of blood glucose, hemodynamic indicators, and inflammatory factors of the patients in the two groups were compared at T0 (before anesthesia), T1 (2 min after intubation), T2 (5 min after pneumoperitoneum), and T3 (60 min after surgery). Mini-Mental State Examination (MMSE) cognitive function scores were compared at T0 (before anesthesia), T4 (6 h after surgery), and T5 (72 h after surgery) between the two groups. The anesthetic effect and the incidence of adverse reactions were also compared between the two groups. The heart rate (HR), oxygen saturation (SpO2) and average artery pressure decreased slightly and then increased after the surgery was started; whereas, the levels of the serum inflammatory factors first increased and then decreased, to return to their initial levels. MMSE scores of the patients in two groups at T4 were significantly lower than those at T0 (P<0.05), and the MMSE score at T4 was significantly higher in the propofol group than that in the sevoflurane group (P<0.05). The time of spontaneous breathing, verbal response, eye opening, and extubation in the propofol group was significantly shorter than that in the sevoflurane group (P<0.05). The incidence of adverse reactions in the propofol group was lower than that in the sevoflurane group. The effect of propofol is less than that of sevoflurane, thus propofol is more suitable for the anesthesia of patients with T2DM and GC.

Circulating levels of ATP is a biomarker of HIV cognitive impairment.

BackgroundIn developed countries, Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART), but still at least half of the HIV infected population shown signs of cognitive impairment. Therefore, biomarkers of HIV cognitive decline are urgently needed.MethodsWe analyze the opening of one of the larger channels expressed by humans, pannexin-1 (Panx-1) channels, in the uninfected and HIV infected population (n = 175). We determined channel opening and secretion of intracellular second messengers released through the channel such as PGE2 and ATP. Also, we correlated the opening of Panx-1 channels with the circulating levels of PGE2 and ATP as well as cogntive status of the individuals analyzed.FindingsHere, we demonstrate that Panx-1 channels on fresh PBMCs obtained from uninfected individuals are closed and no significant amounts of PGE2 and ATP are detected in the circulation. In contrast, in all HIV-infected individuals analyzed, even the ones under effective ART, a spontaneous opening of Panx-1 channels and increased circulating levels of PGE2 and ATP were detected. Circulating levels of ATP were correlated with cognitive decline in the HIV-infected population supporting that ATP is a biomarker of cognitive disease in the HIV-infected population.InterpretationWe propose that circulating levels of ATP could predict CNS compromise and lead to the breakthroughs necessary to detect and prevent brain compromise in the HIV-infected population.

Molecular insight into RNA polymerase I promoter recognition and promoter melting

RNA polymerase I (Pol I) assembles with core factor (CF) and Rrn3 on the rDNA core promoter for transcription initiation. Here, we report cryo-EM structures of closed, intermediate and open Pol I initiation complexes from 2.7 to 3.7 Å resolution to visualize Pol I promoter melting and to structurally and biochemically characterize the recognition mechanism of Pol I promoter DNA. In the closed complex, double-stranded DNA runs outside the DNA-binding cleft. Rotation of CF and upstream DNA with respect to Pol I and Rrn3 results in the spontaneous loading and opening of the promoter followed by cleft closure and positioning of the Pol I A49 tandem winged helix domain (tWH) onto DNA. Conformational rearrangement of A49 tWH leads to a clash with Rrn3 to initiate complex disassembly and promoter escape. Comprehensive insight into the Pol I transcription initiation cycle allows comparisons with promoter opening by Pol II and Pol III.

Unresponsive wakefulness syndrome: Outcomes from a vicious circle.

Unresponsive wakefulness syndrome: Outcomes from a vicious circle.

2310 A Mysterious Case of Non-Cirrhotic Recurrent Severe Hyperammonemia: What Urea-lly Need to Know

INTRODUCTION: Ammonia is a well-known toxin, mostly studied in Hepatic encephalopathy. While, it is related to severe liver disease in 90% cases, the remaining 10% is constituted by disturbances in its excretion or related to over production from other etiologies. [1] Awareness of hyperammonemia in absence of severe hepatic disease may lead to lifesaving prompt diagnosis and treatment. We present a mysterious case of recurrent severe hyperammonemia without known liver disease. CASE DESCRIPTION/METHODS: A 53 year old male with prior history of well controlled hypertension presented to the emergency department with unresponsiveness. On exam, he was unconscious with occasional spontaneous eye opening and a left gaze preference. CT head and CT angiogram of neck did not reveal any acute abnormalities. Liver enzymes and Bilirubin were normal. Blood alcohol level was 0.089gm/dl%. EEG showed diffuse encephalopathy. Serum ammonia was 705 umol/L. He was started on lactulose. His mentation improved in a day and repeat serum ammonia was 25umol/L. Ultrasound liver and CT abdomen ruled out cirrhosis and gall bladder disease. He was discharged home with a prescription of lactulose. He returned to the ED with another episode of unresponsiveness a month later and was found to have elevated serum ammonia of 213 umol/L. Levetiracetam was started empirically with suspicion of recurrent seizures causing this unresponsiveness. He continued to have similar episodes of hyperammonemic encephalopathy. Orotic acid in urine was high (&gt;200 mmol/mol creatinine ), clinching the diagnosis of ornithine transcarbamylase (OTC) deficiency. He was advised to consume a low protein diet and was prescribed L-carnitine along with lactulose. DISCUSSION: Ammonia directly affects neuronal electric activity by inhibiting the generation of both excitatory and inhibitory postsynaptic potentials. Secondary hyperammonemia occurs commonly in the presence of hepatic disorders leading to portosystemic encephalopathy. Less common causes include drugs like valproate, post-chemotherapy, gastric bypass surgery. Causes of primary hyperammonemia in adults include milder forms of urea cycle enzyme deficiencies like OTC, argininosuccinate lyase. Noncirrhotic hyperammonemia as a cause of altered mental status remains a diagnosis of exclusion and requires high index suspicion. Treatment options include lactulose, l-carnitine, and drugs to lower cerebral edema if patient has MRI findings. Liver transplantation is an important treatment modality in urea-cycle disorders.

Circulating Levels of ATP Is a Biomarker of HIV Cognitive Impairment

Background: In developed countries, Human Immunodeficiency Virus type-1 (HIV-1) infection has become a chronic disease despite the positive effects of anti-retroviral therapies (ART) but still at least half of the HIV infected population shown signs of cognitive impairment. Therefore, biomarkers of HIV cognitive decline are urgently needed. Methods: We analyze the opening of one of the larger channels expressed by humans, pannexin-1 channels, in the uninfected and HIV infected population (n=175). Upon opening several intracellular second messengers are released into the extracellular space including PGE2 and ATP in serum/plasma. We correlated the cognitive status of the patients with circulating levels of both factors upon a visit to the clinic. Findings: Here, we demonstrate that pannexin channels on fresh PBMCs from uninfected individuals are closed. In contrast, all HIV-infected individuals analyzed, even the ones under effective ART, had a spontaneous opening of pannexin-1 channels and increased circulating levels of PGE2 and ATP. These results suggest that even low or undetectable levels of HIV result in chronic inflammation and opening of pannexin-1 channels. Furthermore, we found that circulating levels of ATP, but not PGE2, correlated with the cognitive status of people living with HIV. Interpretation: We propose that circulating levels of ATP could predict CNS compromise and lead to the breakthroughs necessary to detect and prevent brain compromise in the HIV-infected population. Funding Statement: This work was funded by The National Institute of Mental Health grant, MH096625, the National Institute of Neurological Disorders and Stroke, NS105584, and UTMB internal funding (to E.A.E). Research in the Geiger (J.D.G.) laboratory was supported by the National Institute of General Medical Sciences under award numbers P30GM100329 and U54GM115458, the National Institute of Mental Health under award numbers R01MH100972 and R01MH105329, the National Institute of Neurological Diseases and Stroke under award number R01NS065957, and the National Institute of Drug Abuse under award number 2R01DA032444. The NNTC is made possible through funding from the NIMH and NINDS by the following grants: Manhattan HIV Brain Bank (MHBB): U24MH100931; Texas NeuroAIDS Research Center (TNRC): U24MH100930; National Neurological AIDS Bank (NNAB): U24MH100929; California NeuroAIDS Tissue Network (CNTN): U24MH100928; and Data Coordinating Center (DCC): U24MH100925. The authors also acknowledge the New Jersey and New York Blood Center, the Alfred P. Sloan Foundation Minority fellowship (to S.V.) and Mount Sinai NeuroAIDS Disparities Summer Institute, R25 MH080663 (to S.V. trainee). Declaration of Interests: The authors stated: None. Ethics Approval Statement: Patients gave written, informed consent for the provision of blood for the purposes of HIV research before inclusion in the current CHARTER pilot study. The protocol for blood collection and analysis was approved by the Mount Sinai, Rutgers University and University of Texas Medical Branch Institutional Review Board (Protocol Numbers, Pro20140000794, Pro2012001303, 18-0136, 18-0135, 18-0134).

Molecular Dynamics Simulations of the “Breathing” Phase Transformation of MOF Nanocrystallites

AbstractThe displacive phase transformation of metal‐organic frameworks (MOFs), referred to as “breathing,” is computationally investigated intensively within periodic boundary conditions (PBC). In contrast, the first‐principles parameterized force field MOF‐FF is used to investigate the thermal‐ and pressure‐induced transformations for non‐periodic nanocrystallites of DMOF‐1 (Zn2(bdc)2(dabco); bdc: 1,4‐benzenedicarboxylate; dabco: 1,4‐diazabicyclo[2.2.2]octane) as a model system to investigate the effect of the PBC approximation on the systems' kinetics and thermodynamics and to assess whether size effects can be captured by this kind of simulation. By the heating of differently sized closed pore nanocrystallites, a spontaneous opening is observed with an interface between the closed and open pore phase moving rapidly through the system. The nucleation temperature for the opening transition rises with size. By enforcing the phase transition with a distance restraint, the free energy can be quantified via umbrella sampling. The apparent barrier is substantially lower than for a concerted process under PBC. Interestingly, the barrier reduces with the size of the nanocrystallite, indicating a hindering surface effect. The results demonstrate that the actual free energy barriers and the importance of surface effects for the transformation under real conditions can only be studied beyond PBC.