bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-026 Association of Inflammatory Markers with Depressive Symptoms Across the Perinatal Period
Authors: Braybrook Emma , English Sarah , Sorinola Olanrewaju , Blacklay Jayne , Forbes-Robertson Sarah , Grammatopoulos Dimitris
Published: May 2020

Perinatal depression (PND) is a mood disorder affecting 10-15% of women during pregnancy and postpartum. Its aetiology is complex with contribution from both genetic background and psychosocial as well as environmental stressors that determine individual responses shaped by chronic and acute disease burden (1). It is thought that the molecular basis of PND involves dysregulation of the HPA axis associated with neurotransmitter and neuroactive steroids imbalance. Inflammation appears to be a contributing mechanism, with increased levels of cytokines exerting adverse effects on serotonin metabolism, neuroplasticity and HPA hyperactivity (2). With only 50% of women detected through current screening strategies, there is an urgent unmet need for the development of biomarker-based strategies to identify women at risk of PND. In this study we used data and blood samples from the prospective Coventry and Warwickshire PND study; we investigated for inflammatory markers associated with depressive symptoms, assessed using the Edinburgh Postnatal Depression Score (EPDS) questionnaire between 24-29 weeks of gestation and again 6-10 weeks postpartum. A cut-off score of 10 categorize ‘high’ or ‘low’ risk for depression. Blood samples collected at 28 weeks of gestation were profiled for either IL-6 and IL-10 levels or a panel of 92 inflammatory markers. Individual inflammatory markers were compared across groups using Welch’s ANOVA. Results suggest that IL-10 levels were significantly correlated with EPDS score, exerting a protective effect (r= -.10), with reduced levels in the highest severity category (EPDS ≥ 15). The IL-6/IL-10 ratio was also associated with a raised EPDS score (r=.10, p=.01), as well as delivery complications (r=.09). The highest IL-6/IL-10 ratio is observed in women who had emergency caesarean section. Bayes’ theorem analysis suggested that IL-6/IL-10 ratio could be used as a negative screen to rule out low risk pregnancies. From the 92 inflammatory markers, 14 analytes were below the limit of detection for more than 50% of samples and so were excluded from further analysis. Upon comparison of groups determined by antenatal and postnatal EPDS scores, 29 markers displayed a significance value of P<0.05. Upon the application of post hoc tests, 8 markers including: STAM-BP, SIRT2, CD40, CASP8 and ADA, all associated with apoptotic processes, remained statistically significant in pregnant women with raised antenatal EPDS scores. This data support an association between inflammatory markers and perinatal depression and adverse pregnancy outcomes. Detailed quantitative analysis of such biomarker signatures at different stages of pregnancy, might lead to early detection of disease and application of targeted treatment. (1) Pariante, C. M. & Lightman, S. L. (2008) Trends Neurosci, 31 (9): 464-468. (2) Raison et al., (2006) Trends Immunol, 27 (1): 24-31.
SAT-190 Are Pet Scans Needed in Evaluating Lipid Rich Adrenal Adenomas?
Authors: Castellanos-Diaz Jessica , Mathews Sherin Elsa , Drane Walter , Staal Stephen , Ghayee Hans Kumar , Kathuria Amita
Published: May 2020

Introduction Adrenal glands are highly vascularized organs and can be the foci of metastatic disease. Incidentally discovered adrenal nodules should be evaluated with CT or MRI imaging and biochemical testing. Metastatic lesions do not have a specific clinical presentation or imaging features but are suspected when there is attenuation greater than 10 HU, presence of calcification, hemorrhage, or abnormal enhancement signals in CT scan or MRI. However, malignant lesions can be present along with benign ones as described here. Clinical Case A 74-year-old female initially presented with uncontrolled hypertension in 2002, at which time she was found to have a left adrenal incidentaloma. MRI/MRA of the abdomen with and without gadolinium contrast showed a 2.5 x 2.6 cm left adrenal nodule, described as a benign lipid rich adrenal adenoma. Biochemical testing revealed no evidence of pheochromocytoma, hyperaldosteronism, or hypercortisolism. Follow-up CT scan in 2003 showed the left adrenal nodule was slightly larger (3.0 x 2.5 cm) but remained lipid rich (<10 HU). There was also a new sub-centimeter nodule in the left medial-posterior limb with similar appearance. In the interim, she was diagnosed with a melanoma on her back in 2003, which was resected without any evidence of invasion. In 2004, abdominal MRI with and without gadolinium contrast showed stable left adrenal nodules. As she continued to have persistent hypertension, uncontrolled with several medications, biochemical work-up for pheochromocytoma, hyperaldosteronism, and hypercortisolism was repeated and was again negative. Surveillance CT imaging in 2005 did not show any changes to her adrenal adenomas. In 2016, she presented to the emergency room with a hemorrhagic cerebrovascular accident. MRI of the brain was consistent with metastatic lesions. CT scan of the chest, abdomen and pelvis showed metastatic lesions in the lungs, liver, bone, and spleen. There was a new 8 mm right adrenal nodule noted with no changes in the left adrenal nodules. Biopsy of a subcutaneous chest wall nodule revealed metastatic melanoma. Thus, she was started on palliative immunotherapy with nivolumab. During her follow-up, she had a series of PET CT scans over a 6 month period, which showed increasing size (up to 4.3 cm) and FDG uptake in the left adrenal nodule. Surprisingly, the left adrenal nodule had a predominantly fatty density (mean of 5 HU) but with an area of hyperdensity which could represent either an adenoma with a coexisting metastatic lesion or angiomyolipoma. Biopsy of the left adrenal nodule revealed a metastatic melanoma. Conclusion This case describes a benign adrenal nodule coexistent with a metastatic lesion. As the patient had metastatic melanoma, a PET-CT was ordered. Melanoma is known to metastasize to the adrenal. This case serves to remind clinicians to perform a careful medical history as management and outcomes can be affected.
SAT-601 Development of a Protocol for Stellate and Celiac Ganglia Dissection for Characterization of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Protein and Receptor Expression in Male and Female Mice Following Cold Acclimation
Authors: Pandher Parleen K , Filatov Ekaterina , Gray Sarah L
Published: May 2020

Pituitary adenylate cyclase-activating polypeptide (PACAP) is being studied to understand the endocrine regulation of energy balance and has been shown to be important in the regulation of the stress response (1,2). Specifically, PACAP has been shown to regulate thermogenesis, an energy burning process regulated by the sympathetic nervous system that contributes to achieving energy homeostasis in response to cold stress and overfeeding. PACAP is expressed in the sympathetic nervous system and is required at the adrenomedullary synapse to maintain epinephrine secretion from the adrenal medulla in response to physiological stress (3). Across the branches of the sympathetic nervous system, PACAP receptor expression is most well characterized in the superior cervical ganglia (SCG) (4). However, a detailed characterization of PACAP and its receptors has not been performed in ganglia whose postganglionic fibres innervate adipose tissues (stellate and celiac ganglia) in response to thermogenic stress. We hypothesized that PACAP is produced by preganglionic neurons innervating the stellate and celiac ganglia, and act on PACAP receptors expressed on the post-ganglionic neurons, and this expression will be upregulated in response to chronic cold stress. Due to their small and amorphous shape, we have developed a protocol to reliably isolate the stellate and celiac ganglia and validate their identity through the presence of tyrosine hydroxylase mRNA, using adrenal and SCG samples as positive controls. PACAP receptor expression (VPAC1, VPAC2, PAC1) was examined in the ganglia utilizing real-time PCR, and PACAP protein was visualized in the ganglia of transgenic mice that express eGFP under the control of the PACAP promoter (PACAP-eGFP mice) (5). This research demonstrates the expression of PACAP receptors in ganglia whose postganglionic fibres innervate adipose tissue, enhancing our understanding of PACAP’s role in the SNS, and its contribution to the regulation of adaptive thermogenesis. References: (1) Gray et al., Pacap: Regulator of the stress response. In: Fink G, ed. Stress: Physiology, biochemistry, and pathology. 2019:279-291. (2) Mustafa, Adv Pharmacol. San Diego, Calif:445-457. (3) Eiden et al., Pflungers Arch. 2018 Jan;470(1):79-88. (4) Braas et al., J Biol Chem. 1999 Sep 24;274(39):27702-27710. (5) Condro et al., J Comp Neurol. 2016 Dec 15; 524(18):3827-3848.
SUN-735 Functional Analysis of Testis-Specific Noncoding Genes in Estrogen-Dependent Transcription
Authors: Choudhari Ramesh , Yang Barbara , Ramos Enrique Ivan , Zilaie Mina , Sanchez-Michael Laura A , Gadad Shrikanth S
Published: May 2020

Emerging studies have shown that germ cell (GC)-specific genes play critical roles in several cancers. The expression of these genes is tightly regulated and restricted to testis; however, many of them escape regulation and become aberrantly expressed in tumors. Interestingly, our genomic analysis suggests that several of these genes are long noncoding RNAs (lncRNAs) and are located at regions previously considered to be gene deserts in the human genome. In this regard, we used an integrated genomic approach to identify GC-lncRNA genes that are overexpressed in breast cancer. Further, by incorporating gene expression analysis from RNA-seq data from MCF-7 and T47D breast cancer cells, we generated a comprehensive list of estrogen-regulated GC-lncRNA genes. We hypothesize that GC-lncRNA genes regulate estrogen-dependent signaling in breast cancer. The selected genes: (a) CAERRC (Chromatin Associated Estrogen-Regulated RNA in Cancer, (b) LncRNA568, (c) LncRNA16 are primate-specific, and exclusively expressed in testis. All of them are regulated by estrogen, and their expression predicts poor outcome in ERα+ breast cancer patients. They have now been fully annotated (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure), and cloned. Further, we have created gene-specific KO MCF-7 cell lines using CRISPR to study their molecular roles. Our data suggest that these genes regulate estrogen-dependent gene expression and tumor growth in breast cancer cells. Genome-wide analysis of ERα binding and gene expression data indicate that they play a critical role in the estrogen-dependent transcription. Collectively, our results suggest that GC-genes, including CAERRC, LncRNA568, and LncRNA16, are excellent targets with prognostic and therapeutic potential in ER+ breast cancers.
SAT-068 Bewilderment! Sex Chromosome Non-Invasive Prenatal Screening (NIPS) Results Differ from Phenotype and Postnatal Karyotype
Authors: Perez-Garcia Eliana Melissa , Shahid Nabiha , Yatsenko Svetlana , Schneck Francis Xavier , Witchel Selma Feldman
Published: May 2020

Background

NIPS uses cell-free DNA in maternal serum to identify fetal aneuploidies including sex chromosome aneuploidies (SCA).1 Despite reports of high sensitivity and specificity, NIPS results, phenotype, and postnatal karyotype may be inconsistent. This situation generates parental anxiety and physician apprehension especially when the apparent genital phenotype differs from the NIPS result. We report four cases involving genotype-phenotype discordance in infants with disorders of sex development (DSD).

Case 1:

Female infant with complex congenital heart disease had inconclusive NIPS results. Postnatal karyotype was 46,XY karyotype (positive for SRY gene). Ultrasound [US] confirmed female internal genitalia. Postnatal karyotype on uncultured peripheral blood cells with FISH showed mosaicism [46,XY (85%)/45,X (15%)].

Case 2: Female infant conceived via IVF had 46,XY karyotype on NIPS. Prenatal and postnatal US showed female internal genitalia. Postnatal results showed 46,XX karyotype and Urine FISH analysis reported XX in all examined cells. Maternal karyotype is 46,XX; maternal FISH results are pending.

Case 3: NIPS reported 45,X. Prenatal US showed male external genitalia. Postnatal exam showed male phenotype with right gonad in inguinal region. Cord blood karyotype and FISH analyses showed mosaicism [45,X (56%)/46,XY (44%)] with 4 different Y chromosome rearrangements. Urine FISH showed mosaicism [45,X (95%)/46,XY (5%)]. Testosterone and AMH concentrations were normal.

Case 4: NIPS reported 46,XY karyotype. Prenatal US showed normal female genitalia. Postnatal physical exam revealed low set ears; additional studies revealed horseshoe kidney and atrial septal defect. Cord blood showed mosaicism [45,X (90%)/46,XY (10%)].

Conclusion

Discrepancies between NIPS and postnatal karyotype occur more commonly with SCA than for autosomal aneuploidies.2 Such inconsistencies generate anxiety regarding sex of fetus, suggest a DSD diagnosis, and warrant additional prenatal and postnatal investigations. Testing to prevent missed detection of sex chromosome mosaicism is necessary. Early diagnosis of DSDs benefits the infant and the family. In some instances, NIPS expose undiagnosed maternal factors.3 Most importantly, communication involving parents and both prenatal and postnatal health care providers is essential to promote timely holistic health care for the infant and family.

References

1.Palka C et al., Eur J Obstet Gynecol Reprod Biol X. 2019; 3:100050

2.Ramdaney A et al., Prenat Diagn. 2018;38:841

3.Richardson EJ, et al., Prenat Diagn. 2017;37:1298

Footnotes
MON-471 The Broken Heart That Hid Behind the Goiter
Authors: Newman Samantha Kass , Greenberg Pietra Dale , Saul Shira R
Published: May 2020

Most goiters grow slowly over many years and are often asymptomatic. Although substernal goiters are estimated to represent between 5-24% of all mediastinal masses [1], a majority are benign. Symptoms may include neck fullness, nocturnal or positional dyspnea, or dysphagia due to tracheal and/or esophageal compression [2-3]. We present a case of a patient with new onset dyspnea that was initially attributed to a large intrathoracic goiter, but ultimately was found to be due to severe heart failure.

A 72-year-old man with a history of HTN, type 2 diabetes, and moderate aortic regurgitation presented to his primary care physician with exertional dyspnea, dry cough, and bilateral leg edema for 2 months. He was referred to pulmonology and a chest CT showed a large intrathoracic goiter, measuring 8.5 x 4.6 x 5.3 cm, extending from the left limb of the thyroid into the mediastinum with rightward tracheal and leftward aortic arch displacement. The patient had no prior history of thyroid disease, cancer, or neck radiation. He denied neck fullness, dysphagia, positional or nocturnal dyspnea, though his exertional dyspnea was progressive. Labs revealed that the patient was biochemically euthyroid. Due to concern for malignancy, the patient underwent a biopsy via EBUS/bronchoscopy, which was non-diagnostic. The case was ultimately discussed at cardiothoracic tumor board, and it was determined that since the mass had likely been present for several years and with the surgical risks being high, to continue monitoring with serial imaging.

At this point, the patient’s dyspnea and edema continued to worsen, and he was evaluated with an echocardiogram which showed a severe worsening of ejection fraction in just three months, from 53% to 5%, with global hypokinesis. He was started on diuretics and medical therapy with prominent improvement in his dyspnea. His cardiology team felt this acute decompensation was likely due to coronary artery disease and recommended left heart cardiac catheterization, however the patient declined.

Goiters tend to be asymptomatic and grow slowly over time. Given their intra-thoracic location and ability to prominently deviate the mediastinum, it can be tempting to attribute respiratory symptoms to large substernal goiters. However, when a patient develops acute symptoms, one must always rule out alternative diagnoses.

References

1. Priola AM, Priola SM, Cardinale L, Cataldi A, Fava C. The anterior mediastinum: diseases. Radiol Med. 2006;111(3):312

2. Katlic MR. Wang CA, Grillo HC. Substernal goiter. Ann thorac surg. 1985;39(4):391.

3. Benbakh M, Abou-elfadl M, Rouadi S, Abada RL, Roubal M, Mahtar M. Substernal goiter: experience with 50 cases. Euroepean annals of otorhinolaryngology, head and neck diseases. 2016-02-01, volume 133, issue 1, 19-22.
SAT-117 Refractory Paraneoplastic Non Islet Cell Tumor Hypoglycemia (NICTH) from Hepatocellular Carcinoma Managed with Somatostatin Analogue and Glucocorticoids
Authors: Siddiqui Mahwash Fatima , Vora Amy , Ali Sadia , Mirfakhraee Sasan
Published: May 2020

Non islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome generally seen in tumors of mesenchymal and hepatic origin. This syndrome is characterized by life threatening hypoglycemia caused by over expression of high molecular weight insulin-like growth factor 2 (IGF 2). The main stay of treatment is surgical resection of the tumor with no clear medical management being reported as standard of care.

We present the case of a 72 year old Cambodian man with no history of diabetes mellitus who presented to our institution with severe hypoglycemia complicated by a seizure and was found to have hepatocellular carcinoma (HCC). Hypoglycemia occurred during times of fasting. Laboratory evaluation revealed a serum glucose of 30mg/dl with insulin level of 2.2 mcIU/mL [2.6 - 24.9 mcIU/ml], C-Peptide of 0.17 ng/mL [0.80 - 3.85 ng/ml], BHB <0.1 mmol/L [0.0 - 0.3 mmol/L] and Proinsulin of <0.4 pmol/L [< or = 18.8 pmol/L]. Hypoglycemic agents screening was negative. Insulin Antibody was negative <0.4 U/mL [<0.4 U/mL] and adrenal insufficiency and hypothyroidism was ruled out. Patient was found to have an elevated IGF 2: IGF 1 ratio of 78 confirming the diagnosis of NICTH. IGF 2 level was 780 ng/ml [333 - 967 ng/ml] while IGF-1 was < 10 ng/ml [32-200 ng/ml] He was not a candidate for surgery due to portal vein involvement and tumor radioembolization was unsuccessful. Despite Prednisone dose of 10 mg twice daily and frequent complex carbohydrate meals, he still continued to have hypoglycemia ultimately requiring hospitalization. During hospitalization, he was treated with 50% dextrose infusion, 37.5 grams of dextrose gel every three hours and frequent small meals. Hypoglycemia remained refractory and a trial of diazoxide was ineffective. He was then started on octreotide with titration to 100mg every 8 hours with significant reduction in hypoglycemic episodes. He continues to remain on octreotide, Prednisolone 20mg twice a day, dextrose gel and dextrose infusion. Goal is to wean dextrose infusion and transition him to Pasireotide 40mg monthly.

Hepatocellular carcinoma has been associated with NICTH in the literature. NICTH is characterized by an IGF2:IGF1 ratio >10 as there is no commercially available assay for big IGF II. Definitive treatment involves surgical resection or tumor debulking. Octreotide has antiangiogenic and antineoplastic properties and unfortunately, few studies have shown improved survival and quality of life in patients with advanced HCC. In the case of our patient, tumor was unresectable and NICTH improved with octreotide and prednisolone.
SUN-566 Metabolic Effects of Cross-Hormone Treatments in Transgender Individuals in Taiwan
Authors: Lin Liang-Yu , Liu Yu-Hsien , Wu Tsung-Hui , Lin Yi-Chun
Published: May 2020

Objective:

Many biological differences seen in men and women are driven by relative different level of estrogen and testosterone. Transgender individuals may need gender-affirming intervention like inhibiting of endogenous sex hormones or replenishing cross-hormone to induce physical change to stimulate their expressed or experienced gender. However, recent study has concluded that the incidences of acute cardiovascular events are higher in transwomen receiving transgender hormone therapy (1). Transgender therapy for adults with Testosterone in female to male (FtM); with Estrogen and anti-androgen in male to female (MtF) are frequently prescribed in Taiwan. The aim of this study is to investigate metabolic effects of an altered sex hormone profile on different gender.

Methods:

The study is a retrospective study conducted in a tertiary medical center in Northern Taiwan analyzing biological differences over time for 65 FtM and 45 MtF patients in our endocrine out-patient department. The results from the exams are analyzed separately using paired t-test compared to baseline visit. The transgender individuals are examined at four time points; before the cross-hormone therapy, three, six, and twelve months following sex hormone treatment.

Results:

The primary outcome was that FtM patients showed significant increases in BMI (22.6±0.3 v.s. 23.3±0.4 kg/m2; P<0.001; t=6M), low density lipoprotein cholesterol (124±3 vs.131±3 mg/dL; P=0.03; t=12M), creatinine (0.75±0.01 vs.0.83±0.14 mg/dL; P<0.001; t=12M), and hemoglobin (13.5±0.7 v.s. 15.2±0.19 g/dL; P<0.001; t=12M) compared to the baseline; decreases of high density lipoprotein cholesterol (57±2.1 v.s. 51±2.0 mg/dL; <0.001; t=12M) was also revealed. Patients in MtF group disclosed declines in low density lipoprotein cholesterol (104±3 v.s. 100±3 mg/dL; P=0.05; t=3M), hemoglobin (14.0±0.1 v.s. 13.5±0.1 g/dL; P=0.008; t=12M), uric acid (5.3±0.2 v.s. 4.7±0.2mg/dL; P=0.03; t=12M) and creatinine (0.82±0.01 v.s. 0.79±0.14 mg/dL; P<0.001; t=6M) compared to baseline data. In addition, most of these metabolic effects persisted the follow-up period.

Conclusion:

This observational study revealed the role of cross-hormone treatment in increasing relative cardiovascular risk in FtM transgender individuals.

Reference:

1. Nota, N. M., et al. (2019). “Occurrence of Acute Cardiovascular Events in Transgender Individuals Receiving Hormone Therapy: Results From a Large Cohort Study.” Circulation 139(11): 1461-1462.

Nothing to Disclose: LYL, YHL, THW, YCL
SUN-604 U.S. Prevalence & Mortality of Prader-Willi Syndrome: A Population-Based Study of Medical Claims
Authors: McCandless Shawn E , Suh Marissa , Yin David , Yeh Michael , Czado Shawn , Aghsaei Sina , Li Justin W , Francis Kevin , Hadker Nandini , Stafford Diane E J
Published: May 2020

Prader-Willi syndrome (PWS) is a complex developmental genetic disorder associated with hypotonia, poor feeding in neonates, onset of hyperphagia in early childhood, and shorter overall life expectancy. Prior epidemiology studies of PWS have examined smaller populations, with limited research in a US population. The aim of this study was to provide a contemporary estimate of PWS prevalence and annual all-cause mortality in the US using a large administrative medical claims dataset.

Methods: PWS patients were identified between 2012-2014 via the presence of ≥2 claims with a diagnosis code for PWS on medical claims provided by IQVIA™ Health Plan Claims Data and CMS Medicare fee-for-service claims. Patients were grouped into age bands including: 0-2, 3-8, 9-17, 18-26, 27-49, and ≥50. PWS prevalence and mortality rates were calculated for 2014, then 2018 US census data was used to project rates for the total US population. The presence of select diagnoses and procedures suggestive of a life-threatening event (e.g., mechanical ventilation) with a patient’s prompt disenrollment defined as death in the IQVIA data; vital status is indicated in Medicare data.

Results: Overall US diagnosed PWS prevalence was 2.7 per 100k persons (or 1 per 37,037), a prevalence of 8,870 patients in the US in 2018. Diagnosed PWS prevalence 3.9, 5.2, 4.5, 4.2, 2.5, and 1.1 per 100k persons respectively for age bands 0-2, 3-8, 9-17, 18-26, 27-49, and ≥50. The median age of PWS patients was 21 years. The mortality rate was highest among diagnosed PWS patients aged 0-2 years and lowest among those aged 9-17 years and the overall mortality rate was 2.7%. For all respective age bands 0-2, 3-8, 9-17, 18-26, 27-49, and ≥50, the all-cause mortality rate was 5.4%, 3.0%, 1.4%, 2.1%, 2.4%, and 4.5%. The observed median age of death was 23 years (IQR 6-36)

Conclusions: The diagnosed PWS prevalence of 1 per 37,037 persons estimated for the 2018 US population is comparable to the other reported US prevalence estimate. As the current study describes diagnosed patients, it likely represents a lower bound of true PWS prevalence. Annual PWS mortality is ≥3 times higher than the overall US population (2.7% vs 0.8%). This rate appears unchanged from mortality estimates reported for PWS populations in the last several decades despite significant advances in genetic testing and the availability of growth hormone therapies in the US. Aggressive management of serious comorbid conditions, especially in younger PWS patients, should be a clinical priority.
Preoperative Evaluation of the Frail Patient
Authors: Nidadavolu Lolita S. , Ehrlich April L. , Sieber Frederick E. , Oh Esther S.
Published: May 2020

Perioperative management of older adults is a complex field that is heavily influenced by the clinical heterogeneity of older adults. Frailty—a geriatric syndrome in which a patient is more vulnerable to stressors due to decreases in physical function and reserve—has been indicative of adverse postoperative outcomes. Many tools have been developed to measure frailty that incorporate a variety of factors including physical and cognitive function, comorbidities, self-reported measures of health, and clinical judgment. Most of these frailty assessment tools are able to identify a subset of patients at risk of adverse outcomes including postoperative complications, longer hospital length of stay, discharge to a higher level of care, and mortality. Frailty assessment before surgical interventions can also guide discussions among patients, their families, anesthesiologists, and surgeons to tailor operative plans for patients to mitigate this increased risk. Studies are ongoing to identify interventions in frail patients that can improve postoperative outcomes, but high-quality data in the form of randomized controlled trials are lacking at this time.
Frailty Is Associated With Postoperative Delirium But Not With Postoperative Cognitive Decline in Older Noncardiac Surgery Patients
Authors: Mahanna-Gabrielli Elizabeth , Zhang Kathy , Sieber Frederick E. , Lin Hung Mo , Liu Xiaoyu , Sewell Margaret , Deiner Stacie G. , Boockvar Kenneth S.
Published: May 2020

BACKGROUND:

Postoperative cognitive dysfunction (POCD) and delirium are the most common perioperative cognitive complications in older adults undergoing surgery. A recent study of cardiac surgery patients suggests that physical frailty is a risk factor for both complications. We sought to examine the relationship between preoperative frailty and postoperative delirium and preoperative frailty and POCD after major noncardiac surgery.

METHODS:

We performed a prospective cohort study of patients >65 years old having major elective noncardiac surgery with general anesthesia. Exclusion criteria were preexisting dementia, inability to consent, cardiac, intracranial, or emergency surgery. Preoperative frailty was determined using the FRAIL scale, a simple questionnaire that categorizes patients as robust, prefrail, or frail. Delirium was assessed with the Confusion Assessment Method for the intensive care unit (CAM-ICU) twice daily, starting in the recovery room until hospital discharge. All patients were assessed with neuropsychological tests (California Verbal Learning Test II, Trail Making Test, subtests from the Wechsler Adult Intelligence Scale, Logical Memory Story A, Immediate and Delayed Recall, Animal and Vegetable verbal fluency, Boston Naming Test, and the Mini-Mental Status Examination) before surgery and at 3 months afterward.

RESULTS:

A total of 178 patients met inclusion criteria; 167 underwent major surgery and 150 were available for follow-up 3 months after surgery. The median age was 70 years old. Thirty-one patients (18.6%) tested as frail, and 72 (43.1%) prefrail before surgery. After adjustment for baseline cognitive score, age, education, surgery duration, American Society of Anesthesiologists (ASA) physical status, type of surgery, and sex, patients who tested frail or prefrail had an estimated 2.7 times the odds of delirium (97.5% confidence interval, 1.0–7.3) when compared to patients who were robust. There was no significant difference between the proportion of POCD between patients who tested as frail, prefrail, or robust.

CONCLUSIONS:

After adjustment for baseline cognition, testing as frail or prefrail with the FRAIL scale is associated with increased odds of postoperative delirium, but not POCD after noncardiac surgery.
Functional Outcomes of Frail Patients After Cardiac Surgery: An Observational Study
Authors: Nakano Mitsunori , Nomura Yohei , Suffredini Giancarlo , Bush Brian , Tian Jing , Yamaguchi Atsushi , Walston Jeremy , Hasan Rani , Mandal Kaushik , Schena Stefano , Hogue Charles W. , Brown Charles H.
Published: May 2020

BACKGROUND:

Although frailty has been associated with major morbidity/mortality and increased length of stay after cardiac surgery, few studies have examined functional outcomes. We hypothesized that frailty would be independently associated with decreased functional status, increased discharge to a nonhome location, and longer duration of hospitalization after cardiac surgery, and that delirium would modify these associations.

METHODS:

This was an observational study nested in 2 trials, each of which was conducted by the same research team with identical measurement of exposures and outcomes. The Fried frailty scale was measured at baseline. The primary outcome (defined before data collection) was functional decline, defined as ≥2-point decline from baseline in Instrumental Activities of Daily Living (IADL) score at 1 month after surgery. Secondary outcomes were absolute decline in IADL score, discharge to a new nonhome location, and duration of hospitalization. Associations were analyzed using linear, logistic, and Poisson regression models with adjustments for variables considered before analysis (age, gender, race, and logistic European Score for Cardiac Operative Risk Evaluation [EuroSCORE]) and in a propensity score analysis.

RESULTS:

Data were available from 133 patients (83 from first trial and 50 from the second trial). The prevalence of frailty was 33% (44 of 133). In adjusted models, frail patients had increased odds of functional decline (primary outcome; odds ratio [OR], 2.41 [95% confidence interval {CI}, 1.03–5.63]; P = .04) and greater decline at 1 month in the secondary outcome of absolute IADL score (−1.48 [95% CI, −2.77 to −0.30]; P = .019), compared to nonfrail patients. Delirium significantly modified the association of frailty and change in absolute IADL score at 1 month. In adjusted hypothesis-generating models using secondary outcomes, frail patients had increased discharge to a new nonhome location (OR, 3.25 [95% CI, 1.37–7.69]; P = .007) and increased duration of hospitalization (1.35 days [95% CI, 1.19–1.52]; P < .0001) compared to nonfrail patients. The increased duration of hospitalization, but no change in functional status or discharge location, was partially mediated by increased complications in frail patients.

CONCLUSIONS:

Frailty may identify patients at risk of functional decline at 1 month after cardiac surgery. Perioperative strategies to optimize frail cardiac surgery patients are needed.
Introduction
Authors: Blevins Jeffrey , Williams Daniel
Published: May 2020

Although literature and logic share a number of surprising symmetries and historical contacts, they have typically been seen to occupy separate disciplinary spheres. Declaring a subfield in literary studies — logic and literature — this introduction outlines various connections between literary formalism and formal logic. It surveys historical interactions and reciprocal influences between literary and logical writers from antiquity through the twentieth century, and it examines how literary theory and criticism have been institutionally shadowed by a logical unconscious, from the New Criticism and (post)structuralism to recent debates about historicism and formalism. It further considers how the subfield of logic and literature, in its constitutive attention to form, is neatly positioned to cut across these debates, and it sketches ways of reading at the interface of aesthetics, philosophy of literature, and literary studies that might be energized by an appeal to logical contexts, ideas, and methods.
Introduction
Authors: Rao Anupama , Primel Casey
Published: May 2020

This short essay introduces the essays in the special section “Concept Histories of the Urban,” which considers the poetics and politics of urban transformation in the global South.
Between Publics and Privates
Authors: Solana Vivian
Published: May 2020

This article discusses the hypervisibility of the Sahrawi munaḍila (female militant) within dominant representations of a Sahrawi revolutionary nationalism. Drawing connections between nation-state building processes, the production of space, and gendered subjectivities, it destabilizes assumptions of institutions as devoid of political movement and shows how the spaces of the National Organization of Sahrawi Women allow women to inhabit the position of loyal critic toward their movement's dominant model of female empowerment. These positions reveal transformations to the way in which space is inhabited intragenerationally, and they reflect the regeneration of a Sahrawi female militancy under the conditions of a protracted struggle for decolonization.
The Price of Blood
Authors: Junaid Mohamad
Published: May 2020

The discourse of loyalty produces tense predicaments for those living under counterinsurgency regimes. The essay explores this theme by analyzing the case of a Kashmiri woman who found herself in a political drama when she accepted “blood money” from the person accused of causing her husband's death. The woman's decision accompanied moral turmoil in her village, and rumors of her “betrayal” circulated. However, the turmoil threatened to go beyond this localized setting. It brought to fore the fraught implications of “loyalty” shaped by India's occupation in Kashmir, its nationalist staging of Kashmiris as the subversive other, and schisms within Kashmir's historical independence movement. By tracing how rumors of individual betrayal were laced onto narratives of political treason in the case, the essay reveals the counterinsurgency as the operative context of broken intimate and intercommunity relations in which the personal is always at the threshold of becoming intensely public.
What Are the Politics of Ahmed's What Is Islam?
Authors: Steinmetz-Jenkins Daniel
Published: May 2020

This review looks at how Shahab Ahmed engages with history, political elitism, secularism, and anthropology in his book What Is Islam? The Importance of Being Islamic.
An Islam of One's Own
Authors: Zaman Taymiya R.
Published: May 2020

This review article examines Shahab Ahmed's What Is Islam? The Importance of Being Islamic in light of the book's challenge to the notion that the sharia consists of Islam's orthodox core, and Muslim literary, artistic, and philosophical truths constitute a periphery. Written from a historian's perspective, it draws out the ways in which Ahmed is able to illuminate aspects of the past that might be unfamiliar to modern Muslim readers. It also shows how Ahmed's argument risks flattening Muslim pasts by failing to disengage with the dynamism of historical forces and with how historical texts are embedded in relations of gender and power.
tRNA elbow modifications affect the tRNA pseudouridine synthase TruB and the methyltransferase TrmA
Authors: Schultz Sarah Kai-Leigh , Kothe Ute
Published: May 2020

tRNAs constitute the most highly modified class of RNA. Every tRNA contains a unique set of modifications, and Ψ55, m5U54, and m7G46 are frequently found within the elbow of the tRNA structure. Despite the abundance of tRNA modifications, we are only beginning to understand the orchestration of modification enzymes during tRNA maturation. Here, we investigated whether pre-existing modifications impact the binding affinity or catalysis by tRNA elbow modification enzymes. Specifically, we focused on the Escherichia coli enzymes TruB, TrmA, and TrmB which generate Ψ55, m5U54, and m7G46, respectively. tRNAs containing a single modification were prepared, and the binding and activity preferences of purified E. coli TrmA, TruB, and TrmB were examined in vitro. TruB preferentially binds and modifies unmodified tRNA. TrmA prefers to modify unmodified tRNA, but binds most tightly to tRNA that already contains Ψ55. In contrast, binding and modification by TrmB is insensitive to the tRNA modification status. Our results suggest that TrmA and TruB are likely to act on mostly unmodified tRNA precursors during the early stages of tRNA maturation whereas TrmB presumably acts on later tRNA intermediates that are already partially modified. In conclusion, we uncover the mechanistic basis for the preferred modification order in the E. coli tRNA elbow region.
Specificity in the biosynthesis of the universal tRNA nucleoside N6-threonylcarbamoyl adenosine (t6A)—TsaD is the gatekeeper
Authors: Swinehart William , Deutsch Christopher , Sarachan Kathryn L. , Luthra Amit , Bacusmo Jo Marie , de Crécy-Lagard Valérie , Swairjo Manal A. , Agris Paul F. , Iwata-Reuyl Dirk
Published: May 2020

N6-threonylcarbamoyl adenosine (t6A) is a nucleoside modification found in all kingdoms of life at position 37 of tRNAs decoding ANN codons, which functions in part to restrict translation initiation to AUG and suppress frameshifting at tandem ANN codons. In Bacteria the proteins TsaB, TsaC (or C2), TsaD, and TsaE, comprise the biosynthetic apparatus responsible for t6A formation. TsaC(C2) and TsaD harbor the relevant active sites, with TsaC(C2) catalyzing the formation of the intermediate threonylcarbamoyladenosine monophosphate (TC-AMP) from ATP, threonine, and CO2, and TsaD catalyzing the transfer of the threonylcarbamoyl moiety from TC-AMP to A37 of substrate tRNAs. Several related modified nucleosides, including hydroxynorvalylcarbamoyl adenosine (hn6A), have been identified in select organisms, but nothing is known about their biosynthesis. To better understand the mechanism and structural constraints on t6A formation, and to determine if related modified nucleosides are formed via parallel biosynthetic pathways or the t6A pathway, we carried out biochemical and biophysical investigations of the t6A systems from E. coli and T. maritima to address these questions. Using kinetic assays of TsaC(C2), tRNA modification assays, and NMR, our data demonstrate that TsaC(C2) exhibit relaxed substrate specificity, producing a variety of TC-AMP analogs that can differ in both the identity of the amino acid and nucleotide component, whereas TsaD displays more stringent specificity, but efficiently produces hn6A in E. coli and T. maritima tRNA. Thus, in organisms that contain modifications such as hn6A in their tRNA, we conclude that their origin is due to formation via the t6A pathway.
Audit and Features of VAT Taxation of Construction Companies
Authors: Kashirina M.
Published: May 2020

Th e article describes the main objectives of the audit of VAT-related operations. Th e article deals with problematic, complex and controversial issues of taxation of construction companies related to the value added tax. Possible tax risks in calculating and paying VAT are analyzed.
PHOTOSYNTHETIC PIGMENT CONTENT AS A CONSEQUENTAL RESISTANCE SIGN OF POTATO VARIETIES TO HIGH TEMPERATURE AND MOISTURE LACK
Authors: Bakunov Aleksei , Milekhin Aleksei , Rubtsov Sergei , Shevchenko Sergei
Published: May 2020

The aim of the research is increasing potato yield in dry conditions of the Middle Volga region. The research was carried out on the experimental field of the Samara Scientific Research Institute of Agriculture – branch of the Sa-mara Research Center of the Russian Academy of Sciences. The variety testing plant nursery included 28 varieties of potatoes of domestic selection. Udacha, Zhigulevsky, Arosa and Gala breeds were the standard varieties. The plant material was planted out in two replications with 25 plants in each. To determine the content of photosynthetic pigments, extracts were prepared from ten potato leaves of each breed in 100% acetone. Measurements were per-formed by spectrophotometry. To measure the amount of chlorophyll a, the wavelength of 665 nm, chlorophyll b – 649 nm, and carotenoids – 440 nm were used. The concentration of pigments was determined by using Wettstein formulas. When harvesting, the potato yield was taken into account. The average concentration of chlorophyll a in the studied breeds was 0.92 mg/g, the average concentration of chlorophyll b was 0.62 mg/g, and one of carote-noids was 0.27 mg/g. Potato breeds with high concentration of photosynthetic pigments were identified. A reliable average dependence of the yield of potato breeds on the concentration of chlorophyll b in plants was revealed. The correlation coefficient was 0.42. There is no reliable dependence tested of yield on the concentration of chlorophyll a and carotenoids. Potato productivity is associated with a significant negative relationship with the ratio of both a and b chlorophyll concentrations. The most highly productive varieties were characterized by a high content of two varieties of chlorophyll. A high concentration of chlorophyll b or a minimum ratio of chlorophyll a and b concentra-tions can be tentatively recommended as a consequential sign for identifying potato breeds that are highly adapted to high air temperature and insufficient moisture.
BEEF COWS BODY CONDITION SCORING AND ITS MEASUREMENTS RELATIONSHIP
Authors: Khakimov Ismagil , Mudarisov Rinat , Akimov Aleksandr
Published: May 2020

The purpose of the study is improving the efficiency of breeding work in selection of cows by live weight, body measurements with mandatory consideration of animal condition score. The degree and nature of relationship be-tween live weight and body measurements of beef cows with condition score, regression coefficient were calculat-ed. The research was carried out on beef Hereford and Kazakh white-headed cows. A high positive relationship between live weight, body measurements and the condition score of cows was established. The regression coeffi-cient showed that change in finish by 1 point increases the live weight of Hereford cows of the first group by 46.3 kg, the second – by 44.2 kg, and the third – by 42.1 kg. The cows of the second group have the largest bulk, they signif-icantly exceeded the Hereford and Kazakh white-headed cows of the first and third groups by this indicator. The difference was 51.2 and 45.9 kg, respectively, the coefficients of variability – varied between 4.1 to 9.2%. Hereford Cows of the second group were superior in heart girth (with a difference of 4 cm) to cows of the first group and 10.6 cm to cows of the third group. The coefficients of variability ranged within 12.9 to 27.0 %. In terms to heart girth (by 1.05 and 0.95 cm) and chest depth (by 8.9 and 2.9 cm), the cows of the second group were superior to the cows of the first and the third groups, respectively (the difference is not reliable). The variation coefficients ranged within 10.3 to 15.7% for heart girth and from 13.0 to 16.7% for chest depth.
INFLUENCE OF BISCHOFITE AND PHOSPHATID CONCENTRATE ON PORK PRODUCTIVITY
Authors: Salomatin Viktor , Murtazaeva Ryshidy , Varakin Aleksandr , Kornilova Valentina
Published: May 2020

The aim of the research is improving pork of store pigs. During the scientific and economic experiment, four store pig groups of large white breed were marked during the feeding period. The influence of natural Volgograd bis-chofite and sunflower phosphatide concentrate both separately and mixed in diets was studied, on pork develop-ment from store pigs. The experimental store pig selection into groups was based on the method of pair-analogues. Animals of compared groups received complete feed: in the first period of feeding SK-6 and in the second period SK-7. Feeding results of experimental pigs of compared groups were evaluated by a number of indicators charac-terizing their meat qualities in total. The main indicators of pork are the hot carcass, slaughter weight and yield. It was found that the introduction to the complete feed natural bischofite and phosphatide concentrate individually, as components and in mixed complex, in comparison with the control, contributes accordingly slaughter live weight in store pigs fattening by 7.84 and 9.78 and 10.97%, their hot carcass – by 8.67, 10.37 and 11.92%, carcass exit – by 0.47-0.33 and 0.53% slaughter weight – by 8.97, 11.18 and 12.94% and slaughter yield – by 0.60, 0.80 and 1.10%. Protein content in the average sample of pork, when animals received test components was more, than in control one by 0.45, 0.25 and 0.63%. Store pigs, which used natural bischofite and phosphatide concentrate the absolute increase in live weight, was higher. Higher meat yield was received from fatted store pigs, with additional introduction to the main diet of natural Volgograd bischofite combined with sunflower phosphatide concentrate.
DYNAMICS OF NUTRITION VALUE AND ALFALFA HAYLAGE MICROBIOLOGICAL INDICATORS WHEN USING BIOLOGICAL PRESERVATIVES
Authors: Fattahova Ziliya , Shakirov Kamil' , Sharafutdinov Gazimzyan , Khakimov Ismagil
Published: May 2020

The purpose of the research is increasing the efficiency of using liquid and dry biological preservatives during alfal-fa haylage. Conservation based on use of individual strains or lactic acid bacterium community is a promising direc-tion of resource – saving technologies for foraging. Influence of biologies on organoleptic properties, safety, nutri-tional value and microbiological parameters of alfalfa haylage was studied. The experiment was conducted in 2016-2018 in the laboratory of Agro-Biological Department of Tatar Research Institute of Agriculture of the Kazan Scientific Center of the Russian Academy of Sciences. The object of research is influence of biological preserva-tives on the nutritional properties of alfalfa haylage, and Aislu alfalfa breed herbage. Industrial samples of Ferbak-SIL liquid biological preservatives with and dry Bioamide-3 enzyme free were used for haylage. It was found that, on average, for 3 years of the experiment, the use of preparations led to the improvement of bio-conservation of herbage, optimization of microorganisms and improvement of nutritional properties of alfalfa haylage. Adding liquid Ferbak-SIL bio-preservative with enzymes to alfalfa herbage led to an increase in the safety of dry matter by 2.06%, raw protein – by 0.69%, raw fiber – by 0.37%, raw fat – by 0.19%, exchange energy – by 7.10%, and concentration of lactic acid bacteria-by 230.1%, compared to the control variant. Values of similar indicators in the variants of the experiment with the dry biological product Bioamide-3 enzymes free were, respectively, 0,78, 0,51, 0,11, 0,08, 3,13, 170,8 % in relation to control.