bluuebunny/crossref_metadata_2025 huggingface dataset:
The Policy and Practice Legacy of the New Jersey Medicaid ACO Demonstration Project
Authors: DeLia Derek , Yedidia Michael J.
Published: November 2019

The New Jersey Medicaid Accountable Care Organization (ACO) Demonstration was created with a unique combination of features regarding ACO geography, involvement of managed care organizations (MCOs), and shared savings parameters. Ultimately, the Demonstration did not lead to a sustainable accountable care financing model and shared savings were deemphasized. Instead, the ACOs evolved into community health coalitions focused on coordinating and enhancing a wide range of activities in partnership with state government, private health systems, community leaders, and MCOs. Currently, the state is developing policy parameters to reposition the ACOs as regional partners to implement state-directed population health initiatives.
Non-coding RNA and lung cancer progression
Authors: Ishola Afeez Adekunle , La’ah Anita Silas , Le Hung Dinh , Nguyen Viet Quoc , Yang Yi-Ping , Chou Shih-Jie , Tai Hsiao-Yun , Chien Chian-Shiu , Wang Mong-Lien
Published: November 2019

Lung cancer (LC) is a major killer disease globally. This situation is further supported by yearly increase in new LC cases and its poor 5-year survival which is less than 15%. Although a large percentage of LC cases have been attributed to smoking, a considerable amount of nonsmokers also develops this disease, thereby suggesting a genetic and/or epigenetic undertone to LC development. Several growth-related genes such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) as well as tumor suppressor genes such as p53 have been implicated in LC pathogenesis and progression. Likewise, the genome only contains approximately 1% of coding regions. Hence, noncoding portion of the genome such as noncoding RNAs (ncRNAs) has been studied and discovered to play a cogent role in LC pathogenesis. More precisely, microRNAs (miRNAs) and long ncRNAs (lncRNAs) have been studied for decades. Posttranscriptional gene modulation function of miRNAs is well established and characterized. Likewise, the antagonizing interaction between lncRNAs and miRNAs had also been proven to further control gene expression during healthy and disease conditions like LC. More recently, renewed attention toward circular RNAs [circular RNAs (circRNAs)] study showed that circRNAs can also sponge miRNAs to modulate gene expressions too. Hence, miRNAs, lncRNAs, and circRNAs seem to function within a circuit to optimally determine which gene is needed to be upregulated or downregulated in biological system. Therefore, this review will discuss important ncRNAs, namely miRNA, lncRNA, and circRNA in LC progression. Paracrine effect of exosomal ncRNA will be also reviewed. In addition, the prospect of these ncRNAs in enhancing better LC treatment will be highlighted as well.
Severe Acquired Hypokalemic Paralysis in a Bodybuilder After Self-Medication With Triamterene/Hydrochlorothiazide
Authors: Pfisterer Nikolaus , Stöllberger Claudia , Finsterer Josef
Published: November 2019

Background:

Severe hypokalemia with severe neurological impairment and electrocardiogram (ECG) abnormalities due to the misuse of triamterene/hydrochlorothiazide (HCTZ) in a bodybuilder has not yet been reported.

Case Report:

A 22-year-old bodybuilder developed acute generalized muscle cramps, sensory disturbance of the distal lower and upper limbs, quadriparesis, and urinary retention. These abnormalities were attributed to severe hypokalemia of 1.8 mmol/L (normal range 3.4-4.5 mmol/L) due to misuse of triamterene/HCTZ together with fluid restriction. He was cardiologically asymptomatic, but ECG revealed a corrected QT (QTc) interval of 625 ms. On intravenous application of fluids along with intravenous and oral substitution of potassium, his condition rapidly improved, such that the sensory disturbances, quadriparesis, and bladder dysfunction completely resolved within 2 days after admission.

Conclusions:

Self-medication with diuretics along with fluid restriction may result in severe hypokalemia, paralysis, and ECG abnormalities. Those responsible for the management of bodybuilding studios and competitions must be aware of the potential severe health threats caused by self-medication with diuretics and anabolic steroids. Although triamterene is potassium-sparing, it may enhance the potassium-lowering effect of HCTZ.
Effectiveness of a Deep-learning Polyp Detection System in Prospectively Collected Colonoscopy Videos With Variable Bowel Preparation Quality
Authors: Becq Aymeric , Chandnani Madhuri , Bharadwaj Shishira , Baran Bülent , Ernest-Suarez Kenneth , Gabr Moamen , Glissen-Brown Jeremy , Sawhney Mandeep , Pleskow Douglas K. , Berzin Tyler M.
Published: November 2019

Background:

Colonoscopy is the gold standard for polyp detection, but polyps may be missed. Artificial intelligence (AI) technologies may assist in polyp detection. To date, most studies for polyp detection have validated algorithms in ideal endoscopic conditions.

Aim:

To evaluate the performance of a deep-learning algorithm for polyp detection in a real-world setting of routine colonoscopy with variable bowel preparation quality.

Methods:

We performed a prospective, single-center study of 50 consecutive patients referred for colonoscopy. Procedural videos were analyzed by a validated deep-learning AI polyp detection software that labeled suspected polyps. Videos were then re-read by 5 experienced endoscopists to categorize all possible polyps identified by the endoscopist and/or AI, and to measure Boston Bowel Preparation Scale.

Results:

In total, 55 polyps were detected and removed by the endoscopist. The AI system identified 401 possible polyps. A total of 100 (24.9%) were categorized as “definite polyps;” 53/100 were identified and removed by the endoscopist. A total of 63 (15.6%) were categorized as “possible polyps” and were not removed by the endoscopist. In total, 238/401 were categorized as false positives. Two polyps identified by the endoscopist were missed by AI (false negatives). The sensitivity of AI for polyp detection was 98.8%, the positive predictive value was 40.6%. The polyp detection rate for the endoscopist was 62% versus 82% for the AI system. Mean segmental Boston Bowel Preparation Scale were similar (2.64, 2.59, P=0.47) for true and false positives, respectively.

Conclusions:

A deep-learning algorithm can function effectively to detect polyps in a prospectively collected series of colonoscopies, even in the setting of variable preparation quality.
Effects of Kinesio taping of the knee on proprioception, balance, and functional performance in patients with anterior cruciate ligament rupture
Authors: Liu Kai , Qian Jinghua , Gao Qi , Ruan Bin
Published: November 2019

To investigate whether Kinesio tape (KT) application improves proprioception, balance, and functional performance in patients with anterior cruciate ligament rupture (ACLr).

This retrospective analysis included 48 male patients with surgically-untreated ACLr who attended the Sports Medicine and Rehabilitation Center, Qingdao Municipal Hospital, China between June 2017 and June 2018. KT was applied to induce a detoning effect on the quadriceps muscle and toning effect on the ischiocrural muscles. Proprioception, balance, and functional performance were assessed before and 1 and 7 days after KT application using the Lysholm scale, anteroposterior shift of the tibia (APST), active angle reproduction test (AART), modified star excursion balance test (mSEBT), and single-hop distance (SHD).

KT resulted in significant improvements in Lysholm scale at 1 day (83.00 [6.50] vs. 76.00 [5.25], P < .001) and APST (8.00 [2.00] vs. 10.00 [2.00] mm, P < .001), AART (3.00 [1.00] vs. 4.00 [1.75] degrees, P < .001), SEBT (96.08 [6.62] vs. 83.92 [7.31] %, P < .001) and SHD (120.96 [6.94] vs. 106.46 [9.03] %, P < .001) at 3 hours (median [interquartile range]). However, significant deficits remained when compared with the healthy side. Except for mSEBT posterolateral direction, those effects were maintained at 7 days.

KT has benefits in people with ACLr but cannot fully compensate for functional deficits. KT could be used to assist knee strengthening during rehabilitation.
Intravenous infusion of dexmedetomidine amplifies thoracic epidural analgesic effect after open thoracotomy
Authors: Choi Eun-Ji , Yoon Jung-Pil , Choi Yun-Mi , Park Ju Yeon , Kim Hee Young , Byeon Gyeong-Jo
Published: November 2019

Background:

The anesthetic-sparing effect of dexmedetomidine has led to its use as a general adjuvant. The present study aimed to determine intravenous infusion of dexmedetomidine to epidural analgesia after open thoracotomy.

Methods:

Forty-four patients scheduled for admission to the intensive care unit after open thoracotomy were divided into 2 groups. An epidural catheter was placed at T4 to T7. Thirty minutes before the end of thoracotomy, group D was injected with 0.3 μg/kg/h of dexmedetomidine and group C received an equal dose of normal saline. For patient-controlled epidural analgesia (PCEA), 150 mL of levobupivacaine 300 mg was infused at a rate of 1 mL/h, plus a bolus dose of 3 mL with a lockout time of 30 minutes. The primary outcome evaluated was analgesic efficacy using a visual analog scale (VAS) 48 hours postoperatively. Other outcomes included additional analgesic use, total consumed local analgesia via PCEA, sedation score, blood pressure, heart rate, arterial blood gases, patient satisfaction, and adverse effects.

Results:

The VAS scores in group D were significantly lower than that in group C immediately, 1, 4, 12, 36, and 48 hours after admission to the intensive care unit (P = .016, .009, .015, .002, .001, and .042, respectively). The total dose of additional analgesic was also significantly lower in group D (P = .011). Patient satisfaction was higher in group D (P < .05). There were no significant differences in the other outcomes between groups.

Conclusion:

Intravenous infusion of dexmedetomidine amplifies thoracic epidural analgesic effect after open thoracotomy.
Efficacy of low molecular weight heparin for chronic obstructive pulmonary disease and respiratory failure
Authors: Zhao Dejun , Feng Jun-Fei
Published: November 2019

Background:

Evaluating the efficacy and safety of low molecular weight heparin (LMWH) for patients with chronic obstructive pulmonary disease (COPD) and respiratory failure (RF) is a major purpose of this study.

Methods:

The following electronic databases will be comprehensively retrieved from the inception to July 1, 2019: Cochrane Library, PUBMED, EMBASE, Google Scholar, Web of Science, Allied and Complementary Medicine Database, WANGFANG, and China National Knowledge Infrastructure without language restrictions. All randomized controlled trials related to LMWH for COPD and RF will be included. Two authors will carry out study selection, data collection, and risk of bias assessment independently.

Results:

This study will systematically explore the efficacy and safety of LMWH for COPD and RF. The primary outcome is lung function. The secondary outcomes are severity of dyspnea on exertion, quality of life, body mass index, airflow obstruction; and any expected and unexpected adverse events.

Conclusion:

The findings of this study will provide evidence to judge whether LMWH is an effective treatment for patients with COPD and RF.

PROSPERO registration number:

PROSPERO CRD42019 139631.
Familial hemophagocytic lymphohistiocytosis in a girl with a novel homozygous mutation of STX11
Authors: Guo Xia , Jiang Mingyan , Tang Xue , Li Qiang
Published: November 2019

Rationale:

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare fatal autosomal recessively inherited disease and can be divided into five types. The mortality of untreated patients is up to 95% and it can be healed only after immunochemotherapy for disease control and hematopoietic stem cell transplantation. Clinical data of a girl with late-onset and recurrent hemophagocytic lymphohistiocytosis (HLH) was retrospectively analyzed to determine the etiology and potential pathogenic gene.

Patient concerns and clinical findings:

The proband was a female child patient from a consanguineous marriage family who was 11 years old, and clinically manifested delayed (onset at the age of 4 years and 6 months) and recrudescent HLH. Both of her elder brothers died at the ages of 4 and 5 years, respectively. The patient had a degranulation function defect of CD107a in natural killer (NK) cells, and the degranulation function of cytotoxic T lymphocytes (CTL) obviously declined (ΔMFI: 1.4%, normal ≧2.8%); the degranulation function of NK cells and CTL of her father was also obviously reduced. To identify possible underlying genetic causes, gene mutation analysis was undertaken. A novel homozygous nonsense mutation inSTX11(c.49C>T, p.Q17X) was documented, arising from both her parents.

Diagnosis:

According to the clinical manifestations and detection results ofSTX11, the diagnosis of FHL-type 4 was confirmed and her parents were heterozygotic carriers.

Interventions and outcomes:

Good responses to HLH-2004 chemotherapy had been achieved for each onset, and the maximum remission duration (without taking any drug) was 23 months. The patient has been alive for 82 months since the onset, and has stopped taking dexamethasone and etoposide, but is still on oral cyclosporine to maintain the treatment. She has performed HLA matching and now is actively looking for a donor to prepare hematopoietic stem cell transplantation.

Conclusions:

Relevant gene detections should be implemented at the earliest for young patients from consanguineous marriages and with a family history of HLH so as to provide a basis for etiological diagnosis and radical treatment by hematopoietic stem cell transplantation and provide accurate genetic counseling for family members.
Atypical manifestations of cardiomegaly and nephrotic syndrome in Kawasaki disease
Authors: Wang Liyuan , Sun Xiaomei , Cai Xiaotang , Liu Shunli , Wang Zhiling , Xie Yongmei
Published: November 2019

Rationale:

To examine atypical manifestations of Kawasaki disease (KD) in children.

Background:

Cardiovascular complications during acute KD are a major contributor to its mortality rate. It can involve the pericardium, the myocardium, the endocardium, and/or the coronary arteries; however, cardiomegaly and nephrotic syndrome (NS) during the acute stage of KD have seldom been reported.

Patient concerns:

Two children, each with a fever lasting more than 5 days, were diagnosed with cardiomegaly using echocardiography in the early phase of Kawasaki disease (within 2 weeks). Case 1 was misdiagnosed with NS because of the proteinuria, hypoalbuminemia, and edema present at the onset of the disease.

Diagnoses:

A diagnosis of incomplete KD was based on a constellation of clinical manifestations and symptoms and was supported by laboratory results.

Interventions:

Intravenous immunoglobulin (IVIG) and aspirin were administered, supplemented with and without supplemental steroid therapy (case dependent).

Outcomes:

The clinical manifestations and syndromes of the two cases were completely resolved and their heart size restored to normal within 2 weeks, with no evidence of coronary artery lesions (CAL).

Main lessons:

Physical findings and manifestations are atypical in incomplete KD. Cardiomegaly and nephrotic syndrome can be an early manifestation of KD; cardiomegaly, especially, should be recognized as a possible manifestation of the acute stage of KD. Furthermore, these symptoms can be rapidly relieved by treatment with IVIG, with or without supplemental steroid therapy.
Repeated and progressive rhabdomyolysis due to a novel carnitine palmitoyltransferase II gene variant in an adult male
Authors: Shao Lina , Liu Chunya , Xu Liyuan , Yu Rizhen , Li Yiwen , Chen Maosheng , He Qiang
Published: November 2019

Introduction:

The occurrence of repeated and progressive rhabdomyolysis is rare in clinical settings, particularly in adults. The pathogenesis of rhabdomyolysis is often overlooked due to its rapid recovery. Carnitine palmitoyltransferase (CPT) II deficiency could be a rare etiology of repetitive nontraumatic rhabdomyolysis, and several mutations of CPT II have been reported.

Patient concerns:

A 41-year-old man presented with high fever, general malaise, myalgia, dyspnea, and dark-colored urine, and then progressed to anuria. In the past 15 years, he experienced dark-colored urine twice due to exercise and high fever. Physical examination revealed oliguria, suppurated tonsils, poor hemoglobin saturation, alert consciousness, normal neurological signs and reflexes, hypertension, and tachypnea. Laboratory investigations showed positive test results for inflammation, high serum myogenic enzyme levels, and evidence of acute kidney injury (AKI).

Diagnoses:

Investigations revealed an extremely high serum myogenic enzyme levels and impaired renal function with serum creatinine level of 510 μmol/L, consistent with the diagnosis of rhabdomyolysis, AKI stage 3, and acute respiratory distress syndrome. High levels of acylcarnitine in the serum confirmed the diagnosis of CPT II deficiency. In addition, whole exome sequencing (WES) was conducted in the patient and his mother.

Interventions:

Intubation, ventilator support, and hemodialysis were the major therapeutic interventions at the peak of disease progression. He was then administered valsartan tablets at a dosage of 80 mg per day and L-carnitine supplements.

Outcomes:

WES conducted in the patient and his mother revealed 2 novel mutations of CPT II (c.482G>A and c.1493G>T) in this patient. The patient recovered from the severe AKI but the renal function remained impaired at chronic kidney disease stage 3a.

Conclusion:

Thus, gene examination can help to understand the etiology of repetitive nontraumatic rhabdomyolysis. Accurate diagnosis can be beneficial for providing an individualized treatment for patients with repeated and progressive rhabdomyolysis.
Effectiveness and safety of hypotensive resuscitation in traumatic hemorrhagic shock
Authors: Wang Hua , Chen Mao-Bing , Zheng Xu-Wen , Zheng Qi-Han
Published: November 2019

Background:

Hypotensive resuscitation is an old study. But its benefits and losses are still controversial. In clinic, the method of fluid resuscitation needs more reliable experimental evidence. This study's objective is to systematically evaluate the efficacy of hypotensive resuscitation in patients with traumatic hemorrhagic shock.

Methods and analysis:

Through October 2019, Web of Science, PubMed, the Cochrane Library, EMBASE, and Clinical Trials will be systematically searched to identify randomized controlled trials exploring the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock. Strict screening and quality evaluation will be independently performed on the obtained literature by 2 researchers; outcome indexes will be extracted, and a meta-analysis will be performed on the data using Revman 5.3 software.

Ethics and dissemination:

The stronger evidence about the efficacy of hypotensive resuscitation in traumatic hemorrhagic shock will be provided for clinicians.

Trial registration number:

PROSPERO CRD42019133169.

Strengths of this study:

This study is not only a simple combination of data, but also to verify and discuss the reliability of the results, and provide more convincing evidence for clinicians.

Limitations of this study:

Firstly, according to the previous literature researching, it is found that the number of relevant randomized controlled trials is small and the quality level of the literature is uneven. Secondly, the efficacy of hypotensive resuscitation is discussed for a long time, different trials may take place at different times. Comparability between different trials is reduced.
Acute tubulointerstitial nephritis with germinal centers in antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Lin Zi-Shan , Liu Xiao-Ling , Cui Zhao , Wang Su-Xia , Yu Feng , Zhou Fu-De , Zhao Ming-Hui
Published: November 2019

Rationale:

Occasionally, tubulointerstitial lesions can be found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, significantly isolated tubulointerstitial nephritis (TIN) with germinal centers is rare.

Patient concerns:

A 17-year-old Chinese Han patient showed rapidly progressive glomerulonephritis, anuria, and serum creatinine of 19.4 mg/dL.

Diagnosis:

He had positive ANCA targeting myeloperoxidase (55.0 RU/mL). The renal biopsy showed crescent formation in 100% of glomeruli. Of special note, the glomerular crescents were surrounded by granulomatous inflammation, extensive tubular destruction or disappearance, and massive interstitial infiltration. A diagnosis of AAV was thus made with the involved organ restricted to the kidney.

Interventions:

The patient underwent 7 rounds of plasmapheresis, 3 pulses of methylprednisolone therapy (500 mg per pulse), and oral prednisolone (50 mg/d). Rituximab (500 mg) was used after the plasma exchange treatment.

Outcomes:

ANCA was negative, while anti-modified C-reactive protein (anti-mCRP) antibodies remained positive. The patient was dependent on hemodialysis. We found anti-mCRP antibody in the serum of the patient, with the major epitope on amino acids 35 to 47 of mCRP.

Lessons:

We proposed that the anti-mCRP antibody might play an important role in this case of acute TIN in AAV.
Concomitant occurrence of clinoid and cavernous segment aneurysms complicated with carotid cavernous fistula
Authors: Ting Wang , Richard Seidu A. , Changwei Zhang , Chaohua Wang , Xiaodong Xie
Published: November 2019

Rationale:

Dual aneurysms arising from the internal cerotic artery (ICA) is a very rare occurrence. Clinoid segment aneurysms (CSAs) are often seen at the carotid dural rings while cavernous carotid aneurysms (CCAs) are often a direct communication between the ICA and the cavernous sinus (CS). We present a case of complex concomitant occurrence of a CSA and a CCA complicated with delay aneurysmal rupture (DAR) resulting in carotid cavernous fistula (CCF) after our initial treatment of the patient with pipeline embolization devices (PLEDs)

Patient Concerns:

We present a 64-year old female who we admitted at our institution due to one-year history of double vision. Neurological examinations were unremarkable.

Diagnosis:

Magnetic resonance imaging (MRI) and computer tomography (CT)-scan revealed dual aneurysms on the ICA. Digital subtracting angiogram (DSA) confirmed a small CSA and a large CCA on the right ICA.

Interventions:

We treated both aneurysms with PLED and subsequently observed DAR of CCA as a complication.

Outcomes:

We successfully occluded the fistula with ONYX (ev3, Irvine, CA) via the trans-venous approach.

Lesions:

PLED was the best endovascular treatment option though DAR was inevitable. Although the trans-arterial approach may be the gold standard for the managing of CCF, the complex nature of our case made us opt for trans-venous approach. The trans-venous route is very appropriate for fistulas with complex parent arteries.
Entrapment of the extensor pollicis longus tendon in a pediatric Smith fracture
Authors: Lee Yoon Min , Kim Yun Hwan , Kim Yuna , Sur Yoo Joon
Published: November 2019

Rationale:

Most pediatric distal radius fractures are effectively treated nonoperatively; however, operative intervention is indicated in patients with open and highly unstable fractures, in those with concomitant neurovascular injuries and in patients whom soft tissue interposition between fracture fragments precludes anatomical reduction. Notably, soft tissue interposition between fracture fragments is diagnostically challenging. Surgeons must be mindful of this rare complication for early detection and prompt treatment.

Patient concerns:

A 14-year-old boy presented to the emergency department with left wrist pain after falling from a bicycle. Plain radiography and computed tomography revealed a displaced Smith fracture, which was irreducible by closed reduction, necessitating open reduction and volar plate fixation. The patient reported inability to extend his thumb at his 6-week postoperative follow-up visit.

Diagnosis:

Ultrasonography showed extensor pollicis longus (EPL) tendon entrapment near the fracture site.

Interventions:

A second operation was performed 10 weeks after the first surgery, and intraoperative exploration revealed EPL tendon entrapment. The EPL tendon was torn to shreds; therefore, extensor indicis proprius tendon transfer was performed for EPL tendon reconstruction.

Outcomes:

The patient's thumb motion was completely restored after the second operation.

Lessens:

EPL tendon entrapment in a pediatric Smith fracture is rare. Signs of EPL tendon entrapment include inability to perform active thumb extension, dorsal wrist pain radiating along the course of the EPL tendon, which is exacerbated by thumb flexion, a tenodesis effect elicited on thumb examination, and difficulty in anatomical fracture reduction. Surgical exploration of the EPL tendon is warranted in patients presenting with any of these signs following attempted reduction of a Smith fracture.
Propofol vs desflurane on the cytokine, matrix metalloproteinase-9, and heme oxygenase-1 response during living donor liver transplantation
Authors: Wu Zhi-Fu , Lin Wei-Lin , Lee Meei-Shyuan , Hung Nan-Kai , Huang Yuan-Shiou , Chen Teng-Wei , Lu Chueng-He
Published: November 2019

Background:

We investigated the effects of propofol vs desflurane on ischemia and reperfusion injury (IRI)-induced inflammatory responses, especially in matrix metalloproteinase-9 (MMP-9) downregulation and heme oxygenase-1 (HO-1) upregulation, which may result in different clinical outcomes in liver transplant recipients.

Methods:

Fifty liver transplant recipients were randomized to receive propofol-based total intravenous anesthesia (TIVA group, n = 25) or desflurane anesthesia (DES group, n = 25). We then measured the following: perioperative serum cytokine concentrations (interleukin 1 receptor antagonist [IL-1RA], IL-6, IL-8, and IL-10); MMP-9 and HO-1 mRNA expression levels at predefined intervals. Further, postoperative outcomes were compared between the 2 groups.

Results:

The TIVA group showed a significant HO-1 level increase following the anhepatic phase and a significant MMP-9 reduction after reperfusion, in addition to a significant increase in IL-10 levels after the anhepatic phase and IL-1RA levels after reperfusion. Compared to DES patients, TIVA patients showed a faster return of the international normalized ratio to normal values, lower plasma alanine aminotransferase concentrations 24 hours after transplantation, and fewer patients developing acute lung injury. Moreover, compared with DES patients, TIVA patients showed a significant reduction in serum blood lactate levels. However, there were no differences in postoperative outcomes between the two groups.

Conclusion:

Propofol-based TIVA attenuated inflammatory response (elevated IL-1RA and IL-10 levels), downregulated MMP-9 response, and increased HO-1 expression with improved recovery of graft function and better microcirculation compared with desflurane anesthesia in liver transplant recipients.
Excellence in Postlicensure Interprofessional Palliative Care Education
Authors: Donesky DorAnne , de Leon Kathleen , Bailey Amos , Doorenbos Ardith , Fink Regina , Hurd Caroline , Ling Perri , Kitko Lisa
Published: November 2019

An increasing number of palliative care educational programs strive to meet the workforce need for palliative care clinicians. This growth necessitates development of robust quality standards. The purpose of this Delphi consensus process was to describe high-quality postlicensure interprofessional palliative care education programs. The steering committee, composed of 6 faculty with experience implementing interprofessional palliative care educational programs, developed initial characteristics, definitions, and subcategories, which were refined through a series of 3 iterative Delphi surveys and a public presentation at a national palliative care meeting. More than 50 palliative care clinicians and educators representing multiple professions were invited to participate in the Delphi surveys; 20 completed round 1, 23 completed round 2, and 15 participants completed round 3. The final consensus included 6 characteristics with definitions, and both required and recommended subcategories for each characteristic. Identified characteristics include competencies, content, educational strategies, interprofessional focus, evaluation, and systems integration. This initial description of quality for postlicensure interprofessional palliative care education programs may be used by learners to guide program selection, new or existing program faculty for course development or quality improvement, or professional organizations to evaluate program quality in a program certification or quality award initiative.
Genetic testing for Alzheimer's disease: trends, challenges and ethical considerations
Authors: Rentería Miguel E. , Mitchell Brittany L. , de Lara Amaranta Manrique
Published: November 2019

Purpose of review

Advances in personal genomics have made predictive genetic testing increasingly popular. The purpose of this review is to examine and summarize recent literature regarding the ethical concerns and considerations surrounding genetic testing for Alzheimer's disease.

Recent findings

Four basic bioethical principles can be applied in the context of genetic testing: autonomy, nonmaleficence, beneficence and justice. The concepts of clinical validity, clinical utility and personal utility are also necessary for the ethical deliberation of genetic testing for Alzheimer's disease. Ethical considerations can differ among three distinct settings present in the literature: research, clinical and direct-to-consumer services. Studies have found that the negative psychosocial impact of genetic test results on the individual is limited, but emphasize the importance of pre/posttesting genetic counselling.

The literature should ideally inform policy-making around genetic testing. There exists an urgent need for regulation, particularly in the direct-to-consumer (DTC) market, since interest for testing in this context is rapidly growing. Standardized protocols for disclosure should be developed, and there is a need to find ways to meet the growing need for genetic counselling. Importantly, comprehensive, evidence-based regulation requires that research be conducted in different contexts with more diverse participants.
Desertihabitans brevis sp. nov., an actinobacterium isolated from sand of the Taklamakan desert, and emended description of the genus Desertihabitans
Authors: Liu Shao-Wei , Li Fei-Na , Liu Hong-Yu , Yu Li-Yan , Sun Cheng-Hang
Published: November 2019

A novel actinobacterium, designated strain 16Sb5-5T, was isolated from a sand sample collected in the Taklamakan desert in Xinjiang Uygur Autonomous Region, China. The strain was examined by a polyphasic approach to clarify its taxonomic position. Cells of the isolate were Gram-staining-positive, aerobic, non-motile and short-rod shaped. Strain 16Sb5-5T grew optimally at 37 °C, pH 7.0 and with 0‒2 % (w/v) NaCl. The cell-wall peptidoglycan was of the A3γ type and contained alanine, glycine, glutamic acid and ll-diaminopimelic acid (ll-DAP). Ribose, arabinose and glucose were detected in the whole-cell hydrolysates. The predominant menaquinone was MK-9(H4). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified phospholipid, three unidentified glycolipids and three unidentified lipids. The major whole-cell fatty acids were anteiso-C15 : 0 and iso-C15 : 0. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 16Sb5-5T was closely related to

Desertihabitans aurantiacus

CPCC 204711T (99.8 % similarity) and formed a robust clade with

D. aurantiacus

in the phylogenetic trees. In silico genomic comparisons showed that strain 16Sb5-5T exhibited ANI values of 94.8–94.9 % and GGDC value of 59.5 % to

D. aurantiacus

CPCC 204711T. The genomic G+C content was 73.3 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic analyses, strain 16Sb5-5T could be distinguishable from its closest phylogenetic relative and represents a novel species of the genus

Desertihabitans

, for which the name Desertihabitans brevis sp. nov. is proposed. The type strain is 16Sb5-5T (=KCTC 49116T=CGMCC 1.16553T). The description of the genus

Desertihabitans

has also been emended.
Retrieval of a well-established skill is resistant to distraction: evidence from an implicit probabilistic sequence learning task
Authors: Vékony Teodóra , Török Lilla , Pedraza Felipe , Schipper Kate , Plèche Claire , Tóth László , Janacsek Karolina , Nemeth Dezso
Published: November 2019

The characteristics of acquiring new sequence information under dual-task situations have been extensively studied so far. Such a concurrent task has often been found to affect performance. In real life, however, we mostly perform a secondary task when the primary one is already well-acquired. The effect of a secondary task on the ability to retrieve well-established sequence representations remains elusive. The present study investigates whether accessing a well-acquired probabilistic sequence knowledge is affected by a concurrent task. Participants acquired non-adjacent regularities in a perceptual-motor implicit probabilistic sequence learning task. After a 24-hour offline period, participants were tested on the same sequence learning task under dual-task or single-task conditions. Here we show that although the secondary task significantly prolonged the overall reaction times in the primary task, the access to the previously learned probabilistic representations remained intact. Our results highlight the importance of studying the dual-task effect not only in the learning phase but also during memory access.
Tau deposition is associated with imaging patterns of tissue calcification in the P301L mouse model of human tauopathy
Authors: Ni Ruiqing , Zarb Yvette , Kuhn Gisela A. , Müller Ralph , Yundung Yankey , Nitsch Roger M. , Kulic Luka , Keller Annika , Klohs Jan
Published: November 2019

Brain calcification is associated with several neurodegenerative proteinopathies. Here, we report a new phenotype of intracranial calcification in transgenic P301L mice overexpressing 4 repeat tau. P301L mice (Thy1.2) of 3, 5, 9 and 18-25 months-of-age and age-matched non-transgenic littermates were assessed using in vivo/ex vivo magnetic resonance imaging (MRI) with a gradient recalled echo sequence and micro computed tomography (μCT). Susceptibility weighted images computed from the gradient recalled echo data revealed regional hypointensities in the hippocampus, cortex, caudate nucleus and thalamus of P301L mice, which in corresponding phase images indicated diamagnetic lesions. Concomitantly, µCT detected hyperdense lesions. Occurrence of diamagnetic susceptibility lesions in the hippocampus, increased with age. Immunochemical staining of brain sections revealed bone protein-positive deposits. Furthermore, intra-neuronal and vessel-associated protein-containing nodules co-localized with phosphorylated-tau (AT8 and AT100) in the hippocampus. Protein-containing nodules were detected also in the thalamus in the absence of phosphorylated-tau deposition. In contrast, osteocalcin-containing nodules were vessel-associated, indicating ossified vessels, in the thalamus in absence of phosphorylated-tau. In summary, MRI and µCT demonstrated imaging pattern of intracranial calcification, concomitant with immunohistochemical evidence of formation of protein deposits containing bone proteins along with phosphorylated-tau in the P301L mouse model of human tauopathy. The P301L mouse model may thus serve as a future model to study the pathogenesis of brain calcifications in tauopathies.
hFUT1-based live cell assay to profile α1-2-fucosides enhanced influenza A virus infection
Authors: Hong Senlian , Grande Geramie , Yu Chenhua , Chapla Digantkumar G. , Reigh Natalie , Yang Yi , Izumori Ken , Moremen Kelley W. , Xie Jia , Wu Peng
Published: November 2019

Host cell-surface glycans play critical roles in influenza A virus (IAV) infection ranging from modulation of IAV attachment to membrane fusion and host tropism. Approaches for quick and sensitive profiling of the viral avidity towards a specific type of host-cell glycan can contribute to the understanding of tropism switching among different strains of IAV. In this study, we developed a method based on chemoenzymatic glycan engineering to investigate the possible involvement of α1-2-fucosides in IAV infections. Using a truncated human fucosyltransferase 1 (hFuT1), we were able to create α1-2-linked fucosides in situ on the host cell surface to assess their influence on the host cell binding to IAV hemagglutinin and the susceptibility of host cells toward IAV induced killing. We discovered that the newly added α1-2-fucosides on host cells enhanced the infection of several human pandemic IVA subtypes. These findings suggest that glycan epitopes other than sialic aicds should be taken into consideration for assessing the human pandemic risk of this viral pathogen.
Perceived Stress in First-Year Medical Students and its Effect on Gut Microbiota
Authors: Rusling Matthew Revere , Johnson Joseph , Shoskes Aaron , Jie Chunfa , Yuan Li-Lian
Published: November 2019

Medical students are constantly under stress caused by strenuous medical programs, which may exert persistent physical and psychological effects on their well-being. Using medical students as a model population, this work explores the gut microbiome as a potential contributing mechanism for why individuals exposed to similar stimuli react variably. We evaluated the relationship of gut microbiome composition of first year medical students and stress resilience over a period of 4 months. Our objective was to identify gut microbiome characteristics of individuals that showed long-term stress resilience. Students were voluntarily recruited and screened for lifestyle and environmental factors at 3 timepoints during the first semester. Fecal samples were also collected at each timepoint. In order to identify candidates with stress resilience, their perceived stress and depression levels were normalized and summed to produce a psychologic index score. The most notable finding is a correlation between psychologic resiliency of Bacteriodete:Firmicute abundance as well as a relationship between durable resiliency and microbiome stability. Phylogenetic assembly of participants by microbiome relatedness found that 100% of subjects who were resilient to stress across all timepoints (n=8) were phylogenetically clustered in adjacent positions, showing a high degree of temporal stability. Of participants who were not durably resilient to stress, only 62% of participants (n=8) showed microbiomes that were phylogenetically related across the same 4 month period. We identified 2,102 Operational Taxonomic Units (OTUs) which were unique to the durable resilience group and 94 OTUs which were unique to the susceptible group. Of the 4,794 observed OTUs, 6.1% (n=294) were significantly different between groups. These findings support that the gut microbiome may play an important role in stress resilience at a time scale of 4 months. A better understanding of the role of the gut microbiome in stress resilience may shed light on potential treatment to reduce stress/anxiety in general, as well as to promote wellbeing of our future health care providers and physicians.
The Ccr4-Not complex monitors the translating ribosome for codon optimality
Authors: Buschauer Robert , Matsuo Yoshitaka , Chen Ying-Hsin , Alhusaini Najwa , Sweet Thomas , Sugiyama Takato , Ikeuchi Ken , Cheng Jingdong , Matsuki Yasuko , Gilmozzi Andrea , Berninghausen Otto , Becker Thomas , Coller Jeff , Inada Toshifumi , Beckmann Roland
Published: November 2019

Control of mRNA decay rate is intimately connected to translation elongation but the spatial coordination of these events is poorly understood. The Ccr4-Not complex initiates mRNA decay through deadenylation and activation of decapping. Using a combination of cryo-electron microscopy, ribosome profiling and mRNA stability assays we show recruitment of Ccr4-Not to the ribosome via specific interaction of the Not5 subunit with the ribosomal E-site. This interaction only occurs when the ribosome lacks accommodated A-site tRNA, indicative of low codon optimality. Loss of Not5 results in the inability of the mRNA degradation machinery to sense codon optimality. Our analysis elucidates a physical link between the Ccr4-Not complex and the ribosome providing mechanistic insight into the coupling of decoding efficiency with mRNA stability.
Sex chromosome pairing mediated by euchromatic homology inDrosophilamale meiosis
Authors: Hylton Christopher A. , Hansen Katie , Bourgeois Andrew , Tomkiel John E.
Published: November 2019

To maintain proper ploidy, haploid sex cells must undergo two subsequent meiotic divisions. During meiosis I, homologs pair and remain conjoined until segregation at anaphase.Drosophila melanogasterspermatocytes are unique in that the canonical events of meiosis I including synaptonemal complex (SC) formation, double-strand DNA breaks, and chiasmata are absent. Sex chromosomes pair at intergenic spacer sequences within the heterochromatic rDNA while euchromatin is required to pair and segregate autosomal homologies, suggesting that pairing may be limited to specific sequences. However, previous work generated from genetic segregation assays or observations of late prophase I/prometaphase I chromosome associations fail to differentiate pairing from conjunction. Here, we separately examined the capability of X euchromatin to pair and conjoin using an rDNA-deficient X and a series ofDp(1;Y)chromosomes. Genetic assays showed that duplicated X euchromatin can substitute for endogenous rDNA pairing sites. Segregation was not proportional to homology length, and pairing could be mapped to nonoverlapping sequences within a singleDp(1;Y). Using fluorescentin situhybridization (FISH) to early prophase I spermatocytes, we showed that pairing occurred with high fidelity at all homologies tested. Pairing was unaffected by the presence of X rDNA, nor could it be explained by rDNA magnification. By comparing genetic and cytological data, we determined that centromere proximal pairings were best at segregation. Segregation was dependent on the conjunction protein Stromalin in Meiosis while the autosomal-specific Teflon was dispensable. Overall, our results suggest that pairing may occur at all homologies, but there may be sequence or positional requirements for conjunction.

ARTICLE SUMMARY

Drosophilamales have evolved a unique system of chromosome segregation in meiosis that lacks recombination. Chromosomes pair at selected sequences suggesting that early steps of meiosis may also differ in this organism. Using Y chromosomes carrying portions of X material, we show that pairing between sex chromosomes can be mediated by sequences other than the previously identified rDNA pairing sites. We propose that pairing may simply be homology-based and may not differ from canonical meiosis observed in females. The main difference in males may be that conjunctive mechanisms that join homologs in the absence of crossovers.
Central norepinephrine transmission is required for stress-induced repetitive behavior in two rodent models of obsessive-compulsive disorder
Authors: Lustberg Daniel , Iannitelli Alexa , Tillage Rachel P. , Pruitt Molly , Cameron Liles L. , Weinshenker David
Published: November 2019

Rationale

Obsessive-compulsive disorder (OCD) is characterized by repetitive behaviors exacerbated by stress. Many OCD patients do not respond to available pharmacotherapies, but neurosurgical ablation of the anterior cingulate cortex (ACC) can provide symptomatic relief. Although the ACC receives noradrenergic innervation and expresses adrenergic receptors (ARs), the involvement of norepinephrine (NE) in OCD has not been investigated.

Objective

To determine the effects of genetic or pharmacological disruption of NE neurotransmission on marble burying (MB) and nestlet shredding (NS) in two animal models of OCD.

Methods

We assessed NE-deficient (Dbh -/-) mice and NE-competent (Dbh +/-) controls in MB and NS tasks. We also measured the effects of anti-adrenergic drugs on NS and MB in control mice and the effects of pharmacological restoration of central NE in Dbh -/- mice. Finally, we compared c-fos induction in the locus coeruleus (LC) and ACC of Dbh -/- and control mice following both tasks.

Results

Dbh -/- mice virtually lacked MB and NS behaviors seen in control mice but did not differ in the elevated zero maze (EZM) model of general anxiety-like behavior. Pharmacological restoration of central NE synthesis in Dbh -/- mice completely rescued NS behavior, while NS and MB were suppressed in control mice by anti-adrenergic drugs. Expression of c-fos in the ACC was attenuated in Dbh -/- mice after MB and NS.

Conclusion

These findings support a role for NE transmission to the ACC in the expression of stress-induced compulsive behaviors and suggest further evaluation of anti-adrenergic drugs for OCD is warranted.
Escort-like somatic cells mediate early mouse fetal ovarian development but surface-derived Lgr5+ cells support primordial follicles
Authors: Niu Wanbao , Spradling Allan C.
Published: November 2019

Ovarian murine somatic cells are essential to form first wave medullar follicles and second wave primordial follicles. Using single cell RNA sequencing we characterized the transcriptomes of both somatic and germline ovarian cells during fetal and early neonatal development. Wnt4-expressing somatic cells we term “escort-like cells (ELCs)” interact with incoming germ cells and early developing cysts of both sexes. In the medullar region, ELCs differentiate into the granulosa cells of fast-growing first wave follicles. In contrast, after E12.5, Lgr5+ pre-granulosa cells ingress from the ovarian surface epithelium and replace cortical escort-like cells. These surface-derived cells become the main population of granulosa cells supporting primordial follicles, and differ in transcription from ELC derivatives. Reflecting their different cellular origins, ablation of Lgr5+ cells at E16.5 using Lgr5-DTR-EGFP eliminates second wave follicles, but first wave follicles continue to develop normally and support fertility. Our findings provide striking evidence that somatic cell behavior supporting germline cyst development in mice and Drosophila has been evolutionarily conserved.
Implementation of Bayesian Multiple Comparison Correction in the Second-Level Analysis of fMRI Data: With Pilot Analyses of Simulation and Real fMRI Datasets Based on Voxelwise Inference
Authors: Han Hyemin
Published: November 2019

We developed and tested Bayesian multiple comparison correction method for Bayesian voxelwise second-level fMRI analysis with R. The performance of the developed method was tested with simulation and real image datasets. First, we compared false alarm and hit rates, which were used as proxies for selectivity and sensitivity, respectively, between Bayesian and classical inference were conducted. For the comparison, we created simulated images, added noise to the created images, and analyzed the noise-added images while applying Bayesian and classical multiple comparison correction methods. Second, we analyzed five real image datasets to examine how our Bayesian method worked in realistic settings. When the performance assessment was conducted, Bayesian correction method demonstrated good sensitivity (hit rate ≥ 75%) and acceptable selectivity (false alarm rate < 10%) when N ≤ 8. Furthermore, Bayesian correction method showed better sensitivity compared with classical correction method while maintaining the aforementioned acceptable selectivity.