Radiation-Driven Destruction of Thiophene and Methyl-Substituted Thiophenes.

Thiophene and two derivatives (2-methylthiophene and 3-methylthiophene) have been detected on the surface of Mars with the Sample Analysis at Mars instrument suite onboard NASA's Curiosity rover. Thiophene could serve as a secondary chemical biosignature since the secondary biosynthesis of thiophene is considered an important production pathway. However, it is critical to understand the abiotic formation and destruction of thiophene and its derivatives since these pathways could affect the molecules' stabilities on planetary surfaces over geological timescales. Here, we present the radiolytic destruction kinetics of thiophene, 2-methylthiophene, and 3-methylthiophene as single-component ices and when diluted in water ice at low temperatures. Using infrared spectroscopy, we determined the destruction rate constants and extrapolated our radiolytic half-lives to the surface of Mars, assuming the measured and modeled surface dose rates. We found that our rate constants strongly depend on temperature and presence of water ice. Based on our determined radiolytic half-life for thiophene under conditions most similar to those of thiophene groups in Martian macromolecules, we expect thiophene to be stable on the surface for significantly longer than the Martian surface exposure age of sites in Gale crater where thiophenes have been detected.

Euglycemic diabetic ketoacidosis in the setting of acute intracerebral hemorrhage.

Background: Diabetic ketoacidosis (DKA) is a life-threatening condition among diabetic patients characterized by metabolic anion gap (AG) acidosis of arterial pH <7.30, glucose >250 mg/dL, and positive ketones. The triggers for DKA can be infection, surgery, and, in reported cases, intraparenchymal hemorrhage (IPH). In rare cases of DKA, despite being in active ketoacidosis, glucose levels may be within normal or accepted range. Such a condition is called euglycemic DKA. It has been recently recognized in association with the use of sodium glucose co-transporter-2 (SGLT-2) inhibitors in the treatment of type 2 diabetes. Case Description: An 83-year-old male taking an SGLT-2 inhibitor (empagliflozin) for type 2 diabetes presented with an IPH. His laboratory studies revealed an elevated AG acidosis, an elevated beta hydroxybutyrate, and serum glucose levels within the acceptable range. Urine studies revealed elevated ketones and glucose. The diagnosis of euglycemic DKA was made, and the patient was treated with insulin and glucose infusions. Conclusion: Like hyperglycemic ketoacidosis, euglycemic DKA requires prompt recognition and immediate aggressive medical therapy, but the diagnosis can be challenging, and the treatment using insulin in the setting of a normal glucose can be counterintuitive. Euglycemic DKA can often be missed in the setting of blood glucose not being elevated. Prompt recognition and treatment are critical for successful management.

The role of interventional bronchoscopy in the management of malignant central airway obstruction.

Nearly a third of patients with primary lung cancer present with malignant central airway obstruction (MCAO), and some of them appear to have advanced disease. In these patients, accurate staging is crucial. Although the literature extensively outlines the role of interventional bronchoscopy in palliation, its contribution to refining the staging of patients with MCAO is noteworthy. Here, we present a case of a patient initially diagnosed with stage IV cancer due to a left mainstem tumor causing complete lung collapse. He was referred to our institution for palliative treatment of his cough. Following interventional bronchoscopy, the patient's staging was revised to T1a, and subsequently, he underwent lobectomy without complications.

High power high voltage bias-T for half wave resonators and radio frequency quadrupole couplers.

High power high voltage bias-T units capable of delivering up to 100 kW CW RF power at 176 MHz and up to 4 kV DC were developed at the Soreq Nuclear Research Center for the Soreq Applied Research Accelerator Facility linac. Two separate bias-T units with different requirements were designed for the radio frequency quadrupole couplers and the half wave resonator couplers. The purpose of this bias-T is to prevent multipacting phenomena by application of a high voltage DC bias to inner conductors of RF couplers. Underlying design principles, indigenous development, and successful off-line and on-line tests results are presented.

Investigating a clinically actionable BRAF mutation for monitoring low-grade serous ovarian cancer: A case report.

Low-grade serous ovarian cancer (LGSOC) poses a specific clinical challenge due to advanced presentation at diagnosis and the lack of effective systemic treatments. The aim of this study was to use a precision medicine approach to identify clinically actionable mutations in a patient with recurrent LGSOC. Primary, metastatic and recurrence tissue, and blood samples were collected from a stage IV LGSOC patient. Single-gene testing for clinically actionable mutations (BRAF V600, KRAS and NRAS) and subsequent whole-exome sequencing (WES) were performed. Droplet digital PCR was used to evaluate the presence of an identified BRAF D594G mutation in the matched plasma cell-free DNA (cfDNA). No clinically actionable mutations were identified using single-gene testing. WES identified a BRAF D594G mutation in six of seven tumor samples. The patient was commenced on a MEK inhibitor, trametinib, but with minimal clinical response. A newly designed ddPCR assay detected the BRAF alteration in the matched tissues and liquid biopsy cfDNA. The identification and sensitive plasma detection of a common "druggable" target emphasises the impact of precision medicine on the management of rare tumors and its potential contribution to novel monitoring regimens in this field.

Racial Disparities in Outcomes After Spine Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: Racial disparities are a major issue in health care but the overall extent of the issue in spinal surgery outcomes is unclear. We conducted a systematic review/meta-analysis of disparities in outcomes among patients belonging to different racial groups who had undergone surgery for degenerative spine disease. METHODS: We searched Ovid MEDLINE, Scopus, Cochrane Review Database, and ClinicalTrials.gov from inception to January 20, 2021 for relevant articles assessing outcomes after spine surgery stratified by race. We included studies that compared outcomes after spine surgery for degenerative disease among different racial groups. RESULTS: We found 30 studies that met our inclusion criteria (28 articles and 2 published abstracts). We included data from 20 cohort studies in our meta-analysis (3,501,830 patients), which were assessed to have a high risk of observation/selection bias. Black patients had a 55% higher risk of dying after spine surgery compared with white patients (relative risk [RR], 1.55, 95% confidence interval [CI], 1.28-1.87; I2 = 70%). Similarly, black patients had a longer length of stay (mean difference, 0.93 days; 95% CI, 0.75-1.10; I2 = 73%), and higher risk of nonhome discharge (RR, 1.63; 95% CI, 1.47-1.81; I2 = 89%), and 30-day readmission (RR, 1.45; 95% CI, 1.03-2.04; I2 = 96%). No significant difference was noted in the pooled analyses for complication or reoperation rates. CONCLUSIONS: Black patients have a significantly higher risk of unfavorable outcomes after spine surgery compared with white patients. Further work in understanding the reasons for these disparities will help develop strategies to narrow the gap among the racial groups.

Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics.

Alveolar epithelial type II (AETII) cells are important for lung epithelium maintenance and function. We demonstrate that AETII cells from mouse lungs exposed to cigarette smoke (CS) increase the levels of the mitochondria-encoded non-coding RNA, mito-RNA-805, generated by the control region of the mitochondrial genome. The protective effects of mito-ncR-805 are associated with positive regulation of mitochondrial energy metabolism, and respiration. Levels of mito-ncR-805 do not relate to steady-state transcription or replication of the mitochondrial genome. Instead, CS-exposure causes the redistribution of mito-ncR-805 from mitochondria to the nucleus, which correlated with the increased expression of nuclear-encoded genes involved in mitochondrial function. These studies reveal an unrecognized mitochondria stress associated retrograde signaling, and put forward the idea that mito-ncRNA-805 represents a subtype of small non coding RNAs that are regulated in a tissue- or cell-type specific manner to protect cells under physiological stress.

The Radiation Stability of Thymine in Solid H2O.

Nucleobases are of significant importance to all known organisms, may be an important building block of life, and could be important biosignatures of current or past life. Given their potential significance to the field of astrobiology, it is important to understand the survival of these molecules when subjected to ionizing radiation as is present in a range of extraterrestrial environments. In this work, we present data on the kinetics of the radiolytic destruction of pure thymine and water + thymine ice mixtures at temperatures from 13 to 150 K. Rate constants were measured using in situ infrared spectroscopy, and radiolytic half-lives for thymine were computed for different planetary and interstellar environments. Our results demonstrate that the survival of thymine decreases as the dilution of thymine in water increases. Additionally, we find that thymine survival increases with ice temperature and that this decrease may be related to structure of the ice matrix.

Quantitative Modeling of External Ventricular Drain Output to Predict Shunt Dependency in Aneurysmal Subarachnoid Hemorrhage: Cohort Study.

BACKGROUND: Acute hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH); however, attempts to predict shunt-dependent chronic hydrocephalus using clinical parameters have been equivocal. METHODS: Cohort study of aSAH is treated with external ventricular drainage (EVD) placement at our institution, 2001-2016, via logistic regression. EVD-related parameters included mean/total EVD output (days 0-2), EVD days, EVD days ≤ 5 mmHg, and wean/clamp fails. aSAH outcomes assessed included ventriculoperitoneal shunt (VPS) placement, delayed cerebral ischemia (DCI), radiographic infarction (RI), symptomatic vasospasm (SV), age, and aSAH grades. RESULTS: Two hundred and ten aSAH patients underwent EVD treatment for a median 12 days (range 1-54); 85 required VPS (40%). On univariate analysis, EVD output, total EVD days, EVD days ≤ 5 mmHg, and wean/clamp trial failures were significantly associated with VPS placement (p < 0.01 for all parameters). No EVD output parameter demonstrated a significant association with DCI, RI, or SV. On multivariate analysis, EVD output was a significant predictor of VPS placement, after adjusting for age and clinical and radiological grades; the optimal threshold for predicting VPS placement was mean daily output > 204 ml on days 0-2 (OR 2.59, 95% CI 1.31-5.07). Multiple wean failures were associated with unfavorable functional outcome, after adjusting for age, grade, and VPS placement (OR 1.65, 95% CI 1.10-2.47). We developed a score incorporating age, grade and EVD parameters (MAGE) for predicting VPS placement after aSAH. CONCLUSIONS: EVD output parameters and wean/clamp trial failures predicted shunt dependence in an age- and grade-adjusted multivariable model. Early VPS placement may be warranted in patients with MAGE score ≥ 4, particularly following 2 failed wean trials.

Laparoscopic-Assisted Intra-Abdominal Section of the Lateral Femoral Cutaneous Nerve for Meralgia Paresthetica Following Anterior Hip Arthroplasty.

BACKGROUND: Meralgia paresthetica, a pain syndrome that is caused by injury to the lateral femoral cutaneous nerve, is a well-documented complication after anterior hip arthroplasty (THA). Traditional treatment of this peripheral nerve entrapment syndrome can be complicated in patients who have had THA via an anterior approach owing to the presence of scar in the postoperative bed. CASE DESCRIPTION: In a 70-year-old man, we performed a novel laparoscopic-assisted intra-abdominal approach to treat meralgia paresthetica in the setting of previous anterior THA. CONCLUSIONS: Minimally invasive intra-abdominal treatment of meralgia paresthetica following anterior THA results in durable pain relief. This approach is a helpful alternative to traditional techniques of decompression or section of the lateral femoral cutaneous nerve below the inguinal ligament.

An evaluation of methods for the isolation of nontuberculous mycobacteria from patients with cystic fibrosis, bronchiectasis and patients assessed for lung transplantation.

BACKGROUND: RGM medium is an agar-based, selective culture medium designed for the isolation of nontuberculous mycobacteria (NTM) from the sputum of patients with cystic fibrosis (CF). We evaluated RGM medium for the detection of NTM in patients with CF (405 samples), bronchiectasis (323 samples) and other lung diseases necessitating lung transplantation (274 samples). METHODS: In total, 1002 respiratory samples from 676 patients were included in the study. Direct culture on RGM medium, with incubation at two temperatures (30 °C and 37 °C), was compared with conventional culture of decontaminated samples for acid-fast bacilli (AFB) using both a solid medium (Löwenstein-Jensen medium) and a liquid medium (the Mycobacterial Growth Indicator Tube; MGIT). RESULTS: For all three patient groups, significantly more isolates of NTM were recovered using RGM medium incubated at 30 °C than by any other method (sensitivity: 94.6% vs. 22.4% for conventional AFB culture; P < 0.0001). Significantly more isolates of Mycobacterium abscessus complex were isolated on RGM at 30 °C than by AFB culture (sensitivity: 96.1% vs. 58.8%; P < 0.0001). The recovery of Mycobacterium avium complex was also greater using RGM medium at 30 °C compared to AFB culture (sensitivity: 83% vs. 70.2%), although this difference was not statistically significant and a combination of methods was necessary for optimal recovery (P = 0.21). CONCLUSIONS: In the largest study of RGM medium to date, we reaffirm its utility for isolation of NTM from patients with CF. Furthermore; we show that it also provides an effective tool for culture of respiratory samples from patients with bronchiectasis and other lung diseases.

Presentation and Outcomes After Medical and Surgical Treatment Versus Medical Treatment Alone of Spontaneous Infectious Spondylodiscitis: A Systematic Literature Review and Meta-Analysis.

STUDY DESIGN: Systematic literature review. OBJECTIVES: The aims of this study were to (1) describe the clinical features, disabilities, and incidence of neurologic deficits of pyogenic spondylodiscitis prior to treatment and (2) compare the functional outcomes between patients who underwent medical treatment alone or in combination with surgery for pyogenic spondylodiscitis. METHODS: A systematic literature review was performed using PubMed according to PRISMA guidelines. No year restriction was put in place. Statistical analysis of pooled data, when documented in the original report (ie, number of patients with desired variable and number of patients evaluated), was conducted to determine the most common presenting symptoms, incidence of pre- and postoperative neurologic deficits, associated comorbidities, infectious pathogens, approach for surgery when performed, and duration of hospitalization. Outcomes data, including return to work status, resolution of back pain, and functional recovery were also pooled among all studies and surgery-specific studies alone. Meta-analysis of studies with subgroup analysis of pain-free outcome in surgical and medical patients was performed. RESULTS: Fifty of 1286 studies were included, comprising 4173 patients undergoing either medical treatment alone or in combination with surgery. Back pain was the most common presenting symptom, reported in 91% of patients. Neurologic deficit was noted in 31% of patients. Staphylococcus aureus was the most commonly reported pathogen, seen in 35% of reported cases. Decompression and fusion was the most commonly reported surgical procedure, performed in 80% of the surgically treated patients. Combined anterior-posterior procedures and staged surgeries were performed in 33% and 26% of surgeries, respectively. The meta-analysis comparing visual analog scale score at follow-up was superior among patients receiving surgery over medical treatment alone (mean difference -0.61, CI -0.90 to -0.25), while meta-analysis comparing freedom from pain in patients receiving medical treatment alone versus combined medical and surgical treatment demonstrated superior pain-free outcomes among surgical series (odds ratio 5.35, CI 2.27-12.60, P < .001), but was subject to heterogeneity among studies (I 2 = 56%, P = .13). Among all patients, freedom from pain was achieved in 79% of patients, and an excellent outcome was achieved in 73% of patients. CONCLUSION: Medical management remains first-line treatment of infectious pyogenic spondylodiscitis. Surgery may be indicated for progressive pain, persistent infection on imaging, deformity or neurologic deficits. If surgery is required, reported literature shows potential for significant pain reduction, improved neurologic function and a high number of patients returning to a normal functional/work status.

Ovarian Teratocarcinoma in an Emu (Dromaius novaehollandiae): Histopathological and Immunohistochemical Characterization.

A 17-year-old female emu (Dromaius novaehollandiae) was presented for clinical evaluation due to a 3-week history of anorexia and progressive weight loss. The emu died after sedation. At necropsy examination, the ovary and the majority of the oviduct were effaced by a multinodular cystic mass and accompanied by 6 l of coelomic effusion. Histopathology revealed a neoplasm composed of well-differentiated, poorly organized tissues derived from ectoderm, mesoderm and endoderm. Tissues within the neoplasm expressed glial fibrillary acidic protein, desmin and cytokeratins AE1/AE3, respectively, confirming the diagnosis of teratocarcinoma.

Perspectives of oncology nurses and oncologists regarding barriers to working with patients from a minority background: Systemic issues and working with interpreters.

This study aimed to ascertain the systemic barriers encountered by oncology health professionals (HPs) working with patients from ethnic minorities to guide the development of a communication skills training programme. Twelve medical and five radiation oncologists and 21 oncology nurses were invited to participate in this qualitative study. Participants were interviewed individually or in a focus group about their experiences working with people from minority backgrounds. All interviews were transcribed verbatim and analysed thematically. HPs encountered language and communication barriers in their interactions with patients and their families, which were perceived to impact negatively on the quality and amount of information and support provided. There was a shortage of, and poor processes for engaging, interpreters and some HPs were concerned about the accuracy of interpretation. HPs expressed a need for training in cultural awareness and communication skills with a preference for face-to-face delivery. A lack of funding, a culture of "learning on the job", and time constraints were systemic barriers to training. Oncologists and oncology nurses encounter complex challenges in clinical interactions with minority patients and their families, including difficulties working with interpreters. Formal training programmes targeted to the development of culturally competent communication skills are required.

Psychosocial Screening Among Youth Seeking Weight Management Treatment.

The objectives of this study were to identify rates of, and factors associated with, "at-risk" scores on a brief psychosocial screener among overweight/obese youth seeking weight management treatment, as well as concordance between youth and caregiver reports. A retrospective chart review of 1443 consecutive patients ages 4 to 18 years and their caregivers was conducted. Almost 1 in 4 youth with overweight/obesity presented with psychosocial symptoms in the at-risk range for significant mental health issues based on caregiver report on the Pediatric Symptom Checklist (PSC) and 1 in 6 based on youth self-report on the Youth Pediatric Symptom Checklist (Y-PSC). Concordance between caregiver and youth was fair (agreement 24% to 40%). Higher scores were associated with male sex and older age on the PSC and with indication of depressive disorder in the electronic medical record on the Y-PSC. Conducting a brief psychosocial screen in comprehensive weight management programs is feasible and clinically indicated.

Superior mesenteric artery syndrome: a single centre experience of laparoscopic duodenojejunostomy as the operation of choice.

INTRODUCTION The superior mesenteric artery (SMA) syndrome, or Wilkie's syndrome, is a rare cause of postprandial epigastric pain, vomiting and weight loss caused by compression of the third part of the duodenum as it passes beneath the proximal superior mesenteric artery. The syndrome may be precipitated by sudden weight loss secondary to other pathologies, such as trauma, malignancy or eating disorders. Diagnosis is confirmed by angiography, which reveals a reduced aorto-SMA angle and distance, and contrast studies showing duodenal obstruction. Conservative management aims to increase intra-abdominal fat by dietary manipulation and thereby increase the angle between the SMA and aorta. Where surgery is indicated, division of the ligament of Treitz, anterior transposition of the third part of the duodenum and duodenojejunostomy have been described. METHODS We present four cases of SMA syndrome where the intention of treatment was laparoscopic duodenojejunostomy. The procedure was completed successfully in three patients, who recovered quickly with no short-term complications. A fourth patient underwent open gastrojejunostomy (complicated by an anastomotic bleed) when dense adhesions prevented duodenojejunostomy. CONCLUSIONS The superior mesenteric artery syndrome should be considered in patients with epigastric pain, prolonged vomiting and weight loss. Laparoscopic duodenojejunostomy is a safe and effective operation for management of the syndrome. A multi-speciality team approach including gastrointestinal, vascular and radiological specialists should be invoked in the management of these patients.

Nontuberculous mycobacteria in gastrostomy fed patients with cystic fibrosis.

Multi-drug resistant Mycobacterium abscessus complex (MABSC) is a form of Nontuberculous mycobacteria (NTM) of special, international concern in Cystic Fibrosis (CF). We hypothesised that gastric juice and percutaneous endoscopic gastrostomy (PEG) feeding devices might yield MABSC isolates. Gastric juice and sputa from sixteen adult PEG fed CF patients and five replaced PEG tubes were studied. Bacterial and fungal isolates were cultured. Mycobacterium were identified by rpoB, sodA and hsp65 gene sequencing and strain typed using variable number tandem repeat. Bacteria and/or fungi grew from all gastric juice, sputa and PEG samples. MABSC were detected in 7 patients. Five had MABSC in their sputum. Two had an identical MABSC strain in their sputum and gastric juice and one had the same strain isolated from their PEG tube and sputum. Two patients who were sputum sample negative had MABSC isolated in their gastric juice or PEG tube. MABSC were therefore identified for the first time from a gastric sample in a minority of patients. We conclude that gastric juice and PEG-tubes may be a potential source of MABSC isolates in CF patients, and these findings warrant further study.

Serine Protease Catalysis: A Computational Study of Tetrahedral Intermediates and Inhibitory Adducts.

Peptide boronic acids and peptidyl trifluoromethyl ketones (TFKs) inhibit serine proteases by forming monoanionic, tetrahedral adducts to serine in the active sites. Investigators regard these adducts as analogs of monoanionic, tetrahedral intermediates. Density functional theory (DFT) calculations and fractional charge analysis show that tetrahedral adducts of model peptidyl TFKs are structurally and electrostatically very similar to corresponding tetrahedral intermediates. In contrast, the DFT calculations show the structures and electrostatic properties of analogous peptide boronate adducts to be significantly different. The peptide boronates display highly electrostatically positive boron, with correspondingly negative ligands in the tetrahedra. In addition, the computed boron-oxygen and boron-carbon bond lengths in peptide boronates (which are identical or very similar to the corresponding bonds in a peptide boronate adduct of α-lytic protease determined by X-ray crystallography at subangstrom resolution) are significantly longer than the corresponding bond lengths in model tetrahedral intermediates. Since protease-peptidyl TFKs incorporate low-barrier hydrogen bonds (LBHBs) between an active site histidine and aspartate, while the protease-peptide boronates do not, these data complement the spectroscopic and chemical evidence for the participation of LBHBs in catalysis by serine proteases. Moreover, while the potency of these classes of inhibitors can be correlated to the structures of the peptide moieties, the present results indicate that the strength of their bonds to serine contribute significantly to their inhibitory properties.