bluuebunny/crossref_metadata_2025 huggingface dataset:
Statins and gastroduodenal endoscopic lesions
Authors: Pantea Monica , Negovan Anca , Voidăzan Septimiu , Macarie Melania , Mocan Simona , Băţagă Simona
Published: December 2018

Experimental studies showed a dose-dependent gastroprotective effect of statins on non-steroidal anti-inflammatory drug-induced endoscopic lesions, modulated by increasing endogenous nitric oxide and prostaglandin production.

We investigated the influence of chronic treatment with statins on the occurrence of endoscopic lesions in patients referred for endoscopic evaluation, adjusted for the most important etiologic and risk factors for peptic ulcer disease and its complications.

A consecutive series of 564 patients who underwent upper digestive endoscopy, stratified according to the severity of endoscopic lesions were recruited. Patients with statin therapy were included in the study group (n = 220), while patients without statins in the control group (n = 344). We correlate the influence of chronic statin therapy (at least 6 months) with factors including age up to 50 years, Helicobacter pylori infection, smoking and drinking habits, ulcer history, gastrotoxic drug consumption (low-dose aspirin [ASA], anticoagulants), and comorbidities.

H pylori infection was more frequent in patients with mild/severe endoscopic lesions vs. no lesions, in both groups, but the difference was not statistically significant (P >.05). Male gender represented a risk factor (P <.01) for mild/severe endoscopic lesions only in the statin group. The estimated risk for developing mild/severe endoscopic lesions with ASA intake decreased from 6.26 to 3.40 (P <.01) when statin therapy was associated. Patients without statins and ischemic coronary artery disease (P <.01; odds ratio [OR] = 2.99; 95% confidence interval (CI):1.88–4.73), heart failure (P = .01; OR = 2.13; 95% CI:1.36–3.34), systemic atherosclerosis (P = .04; OR = 2.30; 95% CI:1.44–3.67) had a statistically significant increased risk for developing mild/severe endoscopic lesions in comparison with patients in the statin group. In multivariate regression analysis models, smoking (P <.01; OR = 2.69; 95% CI:1.73–4.16), ASA (P <.01; OR = 4.54; 95% CI:2.83–7.16), and coronary artery diseases (P = .01; OR = 1.80; 95% CI:1.15–2.82) were independent risk factors for mild/severe endoscopic lesions, while chronic statin therapy (P <.01; OR = 0.31; 95% CI:0.19–0.51) was associated with a protective effect in all models.

The results of the present study support a certain protective role of chronic therapy with statins against endoscopic lesions, especially in ASA consumers or patients with cardiovascular diseases.
Anti-N-methyl-D-aspartate receptor encephalitis
Authors: Li Hua , Guo Yan-ke , Cui Ying-lin , Peng Tao
Published: December 2018

Rationale:

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an auto-immune and paraneoplastic encephalitis with prominent neuropsychiatric manifestations. The N-methyl-D-aspartate receptor is located in the forebrain and hippocampus and plays a role in learning and memory.

Patient concerns:

A 29-year-old female patient with anti-NMDAR encephalitis, was reported and we also reviewed the literature and summarised the characteristics of the cases.

Diagnoses:

In the present study, we reported 1 patient with anti-NMDAR encephalitis diagnosed by the detection of anti-NMDAR antibodies in serum and cerebrospinal fluid (CSF).

Interventions:

The patient received glucocorticoids and anti-epilepsy treatment as well as human immunoglobulin treatment.

Outcomes:

After treatment, the patient gradually regained consciousness and was discharged after 3 months of rehabilitation. At the follow-up 2 months later, the patient had the sequelae of memory impairment and limb movement disorders.

Lessons:

An accurate early diagnosis and active treatment are crucial to the improvement in the prognosis of patients with anti-NMDAR receptor encephalitis.
Controversy regarding when clinically suspicious thyroid nodules should be subjected to surgery
Authors: Jackson Brandon Spencer
Published: December 2018

Background:

The work-up of a thyroid nodule to diagnose malignancy is not always straightforward. There are various international thyroid societies each with their own guidelines on the approach to a thyroid nodule. The aim is therefore to determine whether a clinically suspicious thyroid nodule should be subjected to surgery.

Method:

A review of various international thyroid society guidelines on their approach to a suspicious thyroid nodule.

Results:

Sixty-two relevant articles were identified of which 4 current international thyroid guidelines, consisting of 6 different international societies, were reviewed. The commonalities of each of the thyroid society guidelines are imaging, with ultrasound, and cytopathology as the main diagnostic investigations. The description and the size of the nodule are the 2 most important factors on ultrasound; however, the guidelines vary in their recommendations whether to biopsy a suspicious thyroid nodule. An indeterminate group exists whereby thyroid nodules cannot be confirmed as malignant even with fine needle aspiration cytology (FNA). Although further investigations (Technetium-99m -sestamethoxyisobutylisonitryl scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan, and molecular testing) may assist in the diagnosis, there are limitations. There are differences in the guidelines whether suspicious nodules should be subjected to surgery.

Conclusion:

Ultrasound and cytopathology are the 2 most appropriate investigations to diagnose whether a suspicious thyroid nodule is benign or malignant. The clinician needs to be aware of the differences between the guidelines from the various international thyroid societies, specifically concerning the indeterminate group of patients where a definitive diagnosis cannot be made. Management decisions should be discussed with a thyroid multidisciplinary team for a consensus decision whether or not to subject a patient with a suspicious thyroid nodule to surgery.
Improvement in renal prognosis with prompt hemodialysis in hyperosmolar hyperglycemic state-related rhabdomyolysis
Authors: Chen I-Wen , Lin Cheng-Wei
Published: December 2018

Rationale:

Acute kidney injury is common and correctable in patients with a hyperosmolar hyperglycemic state (HHS). Nevertheless, hyperglycemic crisis may also contribute to the development of rhabdomyolysis, which can worsen renal function and lead to high mortality in such patients.

Patient concerns:

Herein, we report a case of hyperosmolar hyperglycemic state-related rhabdomyolysis and acute renal failure with an excellent outcome.

Diagnosis:

A 26-year-old Asian female with underlying paranoid schizophrenia presented with newly diagnosed type 2 diabetes mellitus complicated with HHS. Her renal function deteriorated rapidly in spite of standard management for hyperglycemic crisis. Rhabdomyolysis was subsequently diagnosed according to the high levels of serum creatine kinase (CK) (37,710 U/L, normal range: 20–180 U/L) and myoglobin (5167.7 ng/mL, normal range: 14.3–65.8 ng/mL).

Interventions:

After treatment failure of intravenous hydration plus loop diuretic agent for rhabdomyolysis related acute renal failure, temporary hemodialysis was performed 3 times to relieve oligouria and pulmonary edema.

Outcomes:

Her renal function recovered well after temporary renal replacement therapy.

Lessons:

Rhabdomyolysis is a complication of HHS. Delayed detection can be fatal, and timely renal replacement therapy can result in an excellent prognosis. Therefore, it is crucial for clinicians to detect and treat such patients as early as possible to avoid impairing their renal function.
Familial intracranial arachnoid cysts with a missense mutation (c.2576C > T) in RERE
Authors: Wang Yubo , Cui Jiayue , Qin Xiaowei , Hong Xinyu
Published: December 2018

Rationale:

Arachnoid cysts are relatively common intracranial space-occupying lesions; nevertheless, familial intracranial arachnoid cysts are extremely rare, with only a few cases having been reported.

Patient concerns:

The proband was a 7-year-old girl who had experienced generalized tonic-clonic seizures 5 times in the 8 days prior to admission. Nine months later, her 6-year-old younger female cousin presented to us with a 3-day history of headache.

Diagnoses:

Brain magnetic resonance imaging (MRI) confirmed the diagnosis of arachnoid cyst for both of the girls.

Interventions:

A cyst-peritoneal shunting and cyst fenestration were performed for the 7-year-old girl and her cousin separately. Sanger sequencing revealed a heterozygous missense mutation (c.2576C > T) in the Arginine-Glutamic Acid Dipeptide Repeats gene (RERE).

Outcomes:

The outcome was favorable and the follow-up was uneventful.

Lessons:

We hypothesize that the mutation in RERE may be associated with the pathogenesis of familial intracranial arachnoid cysts.
A case report and analysis of hypertrophic obstructive cardiomyopathy causing an illusion of aortic stenosis
Authors: Wang Ying , Zhang Yue Ming , Dong Jing Guang , Cheng Li Jie , Jiang Guan Hua , Zheng Jian Wei , Yu Wen Zhou
Published: December 2018

Rationale:

This study aimed to report a case of hypertrophic obstructive cardiomyopathy causing an illusion of aortic stenosis on imaging.

Patient concerns:

A 71-year-old woman presented with chest tightness after activity for 1 year and coughing for 2 months. A systolic 3/6 grade murmur was found in the third intercostals of the left border of sternum. Transthoracic echocardiography, transesophageal echocardiography, and magnetic resonance imaging (MRI) were all suggestive of aortic stenosis and left ventricular outflow tract stenosis.

Diagnosis:

The patient was diagnosed with “severe aortic stenosis (bicuspid deformity), left ventricular outflow tract stenosis (moderate), and grade II cardiac function.“ She was advised aortic valve replacement and left ventricular outflow tract dredging. However, no aortic valve lesion was found during the operation, and the diagnosis was changed to “hypertrophic obstructive cardiomyopathy.”

Interventions and outcomes:

The morrow procedure was performed, and the patient recovered well after the operation. Hypertrophic obstructive cardiomyopathy was found to cause an illusion of aortic stenosis on imaging.

Lessons:

Special attention and rational treatment should be paid to such patients. In addition, further studies are needed to distinguish between the two diseases to reduce misdiagnosis.
Hearing Status in Survivors of Childhood Acute Myeloid Leukemia Treated With Chemotherapy Only: A NOPHO-AML Study
Authors: Skou Anne-Sofie , Olsen Steen Ø. , Nielsen Lars H. , Glosli Heidi , Jahnukainen Kirsi , Jarfelt Marianne , Jónmundsson Guðmundur K. , Malmros Johan , Nysom Karsten , Hasle Henrik
Published: December 2018

Background:

As more children survive acute myeloid leukemia (AML) it is increasingly important to assess possible late effects of the intensive treatment. Hearing loss has only sporadically been reported in survivors of childhood AML. We assessed hearing status in survivors of childhood AML treated with chemotherapy alone according to 3 consecutive NOPHO-AML trials.

Procedure:

A population-based cohort of children treated according to the NOPHO-AML-84, NOPHO-AML-88, and NOPHO-AML-93 trials included 137 eligible survivors among whom 101 (74%) completed a questionnaire and 99 (72%) had otologic and audiologic examination performed including otoscopy (72%), pure tone audiometry (70%), and tympanometry (60%). Eighty-four of 93 (90%) eligible sibling controls completed a similar questionnaire.

Results:

At a median of 11 years (range, 4 to 25) after diagnosis, hearing disorders were rare in survivors of childhood AML and in sibling controls, with no significant differences. None had severe or profound hearing loss diagnosed at audiometry. Audiometry detected a subclinical hearing loss ranging from slight to moderate in 19% of the survivors, 5% had low-frequency hearing loss, and 17% had high-frequency hearing loss.

Conclusions:

The frequency of hearing disorders was low, and hearing thresholds in survivors of childhood AML were similar to background populations of comparable age.
Randomized Controlled Trial of Symptom Management Patient Education for People With Acute Coronary Syndrome
Authors: Stolic Snezana , Lin Frances , Mitchell Marion
Published: December 2018

Background:

Poorly managed acute coronary syndrome symptoms increase the risk of subsequent cardiovascular events.

Purpose:

The aim of this study was to evaluate the effectiveness of symptom management patient education on the knowledge of sublingual nitroglycerin for people with acute coronary syndrome.

Methods:

A randomized controlled trial was used to evaluate the 3-resource intervention. The study was conducted in a 448-bed Australian public hospital. The instrument used was the modified Sublingual Nitroglycerin Interview Schedule.

Results:

A total of 169 participants completed the study. The intervention group significantly improved their knowledge of sublingual nitroglycerin when compared with the control group (P = .002).

Conclusion:

This 3-resource symptom management patient education shows promise in improving sublingual nitroglycerin knowledge for people with acute coronary syndrome.
Human Immunodeficiency Virus Diagnosis After a Syphilis, Gonorrhea, or Repeat Diagnosis Among Males Including non–Men Who Have Sex With Men: What Is the Incidence?
Authors: Tilchin Carla , Schumacher Christina M. , Psoter Kevin J. , Humes Elizabeth , Muvva Ravikiran , Chaulk Patrick , Checkley William , Jennings Jacky M.
Published: December 2018

Background

The release of the first drug for human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) in 2012 marked the beginning of a new era of HIV prevention. Although PrEP is highly efficacious, identifying and ultimately increasing uptake among the highest risk male subgroups remains a challenge.

Methods

Public health surveillance data from 2009 to 2016 was used to evaluate the risk of an HIV diagnosis after a syphilis (ie, primary, secondary, or early latent), gonorrhea, and repeat diagnoses among urban males, including men who have sex with men (MSM) and non-MSM in Baltimore City.

Results

Of the 1531 males with 898 syphilis diagnoses and 1243 gonorrhea diagnoses, 6.8% (n = 104) were subsequently diagnosed with HIV. Within 2 years, 1 in 10 syphilis or gonorrhea diagnoses were followed by an HIV diagnosis among MSM, and 1 in 50 syphilis or gonorrhea diagnoses were followed by an HIV diagnosis among non-MSM. Among non-MSM with gonorrhea, the rate of HIV incidence was 5.36 (95% confidence interval, 2.37–12.14) times higher in those with (vs. without) a subsequent syphilis diagnosis or gonorrhea diagnosis.

Conclusions

Local health care providers should offer PrEP to MSM diagnosed with syphilis or gonorrhea and to non-MSM with a previous gonorrhea diagnosis at time of a syphilis or gonorrhea diagnosis. The high proportion and short time to an HIV diagnosis among MSM after a syphilis or gonorrhea diagnosis suggest immediate PrEP initiation.
Endometrial Carcinoma, Grossing and Processing Issues: Recommendations of the International Society of Gynecologic Pathologists
Authors: Malpica Anais , Euscher Elizabeth D. , Hecht Jonathan L. , Ali-Fehmi Rouba , Quick Charles M. , Singh Naveena , Horn Lars-Christian , Alvarado-Cabrero Isabel , Matias-Guiu Xavier , Hirschowitz Lynn , Duggan Máire , Ordi Jaume , Parkash Vinita , Mikami Yoshiki , Ruhul Quddus M. , Zaino Richard , Staebler Annette , Zaloudek Charles , McCluggage W. Glenn , Oliva Esther
Published: December 2018

Endometrial cancer is the most common gynecologic neoplasm in developed countries; however, updated universal guidelines are currently not available to handle specimens obtained during the surgical treatment of patients affected by this disease. This article presents recommendations on how to gross and submit sections for microscopic examination of hysterectomy specimens and other tissues removed during the surgical management of endometrial cancer such as salpingo-oophorectomy, omentectomy, and lymph node dissection—including sentinel lymph nodes. In addition, the intraoperative assessment of some of these specimens is addressed. These recommendations are based on a review of the literature, grossing manuals from various institutions, and a collaborative effort by a subgroup of the Endometrial Cancer Task Force of the International Society of Gynecological Pathologists. The aim of these recommendations is to standardize the processing of endometrial cancer specimens which is vital for adequate pathological reporting and will ultimately improve our understanding of this disease.
Full-Genome Analysis of Hepatitis C Virus in Japanese and Non-Japanese Patients Coinfected With HIV-1 in Tokyo
Authors: Ishida Yuki , Hayashida Tsunefusa , Sugiyama Masaya , Tsuchiya Kiyoto , Kikuchi Yoshimi , Mizokami Masashi , Oka Shinichi , Gatanaga Hiroyuki
Published: December 2018

Background:

Acute hepatitis C virus (HCV) infection is increasing among HIV-1–infected individuals in Tokyo. Appropriate clinical management is needed.

Setting:

To delineate the epidemiological status of HCV transmission, we analyzed stocked plasma samples of HCV/HIV-1–coinfected patients seen at the largest referral center for HIV care in Tokyo.

Methods:

HCV full-genome sequences were amplified and determined using next-generation sequencing. HCV genotyping and phylogenetic and phylodynamic analyses of thus obtained sequences were performed and combined with the analysis of HIV-1 reverse transcriptase sequences.

Results:

HCV phylogenetic analysis identified 3 dense clusters containing cases of men who have sex with men (MSM) and injection drug users (IDUs). Most of the confirmed acute infection cases were included within these clusters, indicating that the clustered viruses are currently being actively transmitted among HIV-1–infected MSM and IDU. Phylodynamic analysis indicated population expansion of one of these clusters from 2006 to 2008, during which the largest number of HIV-1–infected MSM was diagnosed in Tokyo. HIV-1 reverse transcriptase sequences of HCV-coinfected patients included in the same clusters did not converge together and did not form clusters, but rather diverged in the area of subtype B in the phylogenetic tree, indicating that they acquired HCV infection from individuals different from those from whom they had acquired HIV-1 infection. It is considered that these MSM changed their sexual partners and that IDU changed their drug use groups.

Conclusions:

The results warrant careful monitoring of high-risk groups including MSM and IDU and early introduction of HCV treatment to prevent HCV epidemic.
Computed Tomography Imaging for Novel Therapies of Chronic Obstructive Pulmonary Disease
Authors: Kauczor Hans-Ulrich , Wielpütz Mark O. , Jobst Bertram J. , Weinheimer Oliver , Gompelmann Daniela , Herth Felix J.F. , Heussel Claus P.
Published: December 2018

Novel therapeutic options in chronic obstructive pulmonary disease (COPD) require delicate patient selection and thus demand for expert radiologists visually and quantitatively evaluating high-resolution computed tomography (CT) with additional functional acquisitions such as paired inspiratory-expiratory scans or dynamic airway CT. The differentiation between emphysema-dominant and airway-dominant COPD phenotypes by imaging has immediate clinical value for patient management. Assessment of emphysema severity, distribution patterns, and fissure integrity are essential for stratifying patients for different surgical and endoscopic lung volume reduction procedures. This is supported by quantitative software-based postprocessing of CT data sets, which delivers objective emphysema and airway remodelling metrics. However, the significant impact of scanning and reconstruction parameters, as well as intersoftware variability still hamper comparability between sites and studies. In earlier stage COPD imaging, it is less clear as to what extent quantitative CT might impact decision making and therapy follow-up, as emphysema progression is too slow to realistically be useful as a mid-term outcome measure in an individual, and longitudinal data on airway remodelling are still very limited.
Translocator Protein Localises To CD11b+ Macrophages In Atherosclerosis
Authors: Kopecky Chantal , Pandzic Elvis , Parmar Arvind , Szajer Jeremy , Lee Victoria , Dupuy Alexander , Arthur Andrew , Fok Sandra , Whan Renee , Ryder William J , Rye Kerry-Anne , Cochran Blake J
Published: December 2018

Background: Atherosclerosis is characterized by lipid deposition, monocyte infiltration and foam cell formation in the artery wall. Translocator protein (TSPO) is abundantly expressed in lipid rich tissues. Recently, TSPO has been identified as a potential diagnostic tool in cardiovascular disease. The purpose of this study was to determine if the TSPO ligand, 18F-PBR111, can identify early atherosclerotic lesions and if TSPO expression can be used to identify distinct macrophage populations during lesion progression. Methods and Results: ApoE-/- mice were maintained on a high-fat diet for 3 or 12 weeks. C57BL/6J mice maintained on chow diet served as controls. Mice were administered 18F-PBR111 intravenously and PET/CT imaged. After euthanasia, aortas were isolated, fixed and optically cleared. Cleared aortas were immunostained with DAPI, and fluorescently labelled with antibodies to-TSPO, the tissue resident macrophage marker F4/80 and the monocyte-derived macrophage marker CD11b. TSPO expression and the macrophage markers were visualised in fatty streaks and mature lesions by light sheet microscopy. While tissue resident F4/80+ macrophages were evident in the arteries of animals without atherosclerosis, no CD11b+ macrophages were observed in these animals. In contrast, mature plaques had high CD11b and low F4/80 expression. A ~3-fold increase in the uptake of 18F-PBR111 was observed in the aortas of atherosclerotic mice relative to controls. Conclusions: Imaging of TSPO expression is a new approach for studying atherosclerotic lesion progression and inflammatory cell infiltration. The TSPO ligand, 18F-PBR111, is a potential clinical diagnostic tool for the detection and quantification of atherosclerotic lesion progression in humans.
Dynamics of Notch-dependent transcriptional bursting in its native context
Authors: Lee ChangHwan , Shin Heaji , Kimble Judith
Published: December 2018

Transcription is well known to be inherently stochastic and episodic, but the regulation of transcriptional dynamics is not well understood. Here we analyze how Notch signaling modulates transcriptional bursting during animal development. Our focus is Notch regulation of transcription in germline stem cells of the nematode C. elegans. Using the MS2 system to visualize nascent transcripts and live imaging to record dynamics, we analyze bursting as a function of position within the intact animal. We find that Notch-dependent transcriptional activation is indeed bursty; that wild-type Notch modulates burst duration (ON-time) rather than duration of pauses between bursts (OFF-time) or mean burst intensity; and that a mutant Notch receptor, which is compromised for assembly into the Notch transcription factor complex, primarily modifies burst size (duration x intensity). To our knowledge, this work is the first to visualize regulation of metazoan transcriptional bursting by a canonical signaling pathway in its native context.
SIRT2, ERK and Nrf2 mediate NAD+ treatment-induced increase in the antioxidant capacity of differentiated PC12 cells under basal conditions
Authors: Zhang Jie , Hong Yunyi , Cao Wei , Shi Haibo , Ying Weihai
Published: December 2018

NAD+administration is highly beneficial in numerous models of diseases and aging. It is becoming increasingly important to determine if NAD+treatment may increase directly the antioxidant capacity of cells under basal conditions. In current study we tested our hypothesis that NAD+can enhance directly antioxidant capacity of cells under basal conditions by using differentiated PC12 cells as a cellular model. We found that NAD+treatment can increase the GSH/GSSG ratios in the cells under basal conditions. NAD+can also increase both the mRNA and protein level of γ-glutamylcysteine ligase – a key enzyme for glutathione synthesis, which appears to be mediated by the NAD+-induced increase in Nrf2 activity. These NAD+-induced changes can be prevented by both SIRT2 siRNA and the SIRT2 inhibitor AGK2. The NAD+-induced changes can also be blocked by the ERK signaling inhibitor U0126. Moreover, the NAD+-induced ERK activation can be blocked by both SIRT2 siRNA and AGK2. Collectively, our study has provided the first evidence that NAD+can enhance directly the antioxidant capacity of the cells under basal conditions, which is mediated by SIRT2, ERK, and Nrf2. These findings have suggested not only the great nutritional potential of NAD+, but also a novel mechanism underlying the protective effects of the NAD+administration in the disease models: The NAD+administration can enhance the resistance of the normal cells to oxidative insults by increasing the antioxidant capacity of the cells.
The cortico-striatal circuit regulates sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport
Authors: Jaaro-Peled Hanna , Kumar Sunil , Hughes Dalton , Kim Sun-Hong , Zoubovsky Sandra , Hirota-Tsuyada Yuki , Zala Diana , Sumitomo Akiko , Bruyere Julie , Katz Brittany M. , Huang Beverly , Flores Rafael , Narayan Soumya , Hou Zhipeng , Economides Aris N. , Hikida Takatoshi , Wetsel William C. , Deisseroth Karl , Mori Susumu , Brandon Nicholas J. , Tanaka Motomasa , Ishizuka Koko , Houslay Miles D. , Saudou Frédéric , Dzirasa Kafui , Sawa Akira , Tomoda Toshifumi
Published: December 2018

Sensorimotor information processing that underlies normal cognitive and behavioral traits is dysregulated across a subset of neurological and psychiatric disorders. The cross-disease deficit in sensorimotor gating poses a unique opportunity to integrate hierarchical findings at molecular, cellular, through circuitry levels to obtain an in-depth mechanistic understanding of this process that contributes to brain physiology and pathophysiology beyond categorical segmentation of brain disorders. Based on circuitry recording with wild-type mice, we demonstrated that the cortico-striatal projection mediates sensorimotor gating responses during prepulse inhibition (PPI) task. We also found that these circuitry responses were disrupted in Disc1 locus-impairment (LI) mice, a model representing neuropsychiatric conditions. Thus, we hypothesized that Disc1-mediated molecular and cellular machinery along the cortico-striatal circuit may regulate sensorimotor gating. Anatomical and biochemical analyses of Disc1-LI mice revealed attenuated Bdnf transport along the cortico-striatal circuit. Pharmacologically augmenting Bdnf transport by chronic lithium administration, in part via Ser-421 phosphorylation of Huntingtin (Htt) and its integration into the motor machinery, restored the striatal Bdnf levels and PPI deficits in Disc1-LI mice, suggesting that the Bdnf transport attenuation mechanistically underlies the circuitry and behavioral deficits. These results also shed light on a novel mechanism and utility of lithium that is currently used as a major mood stabilizer in clinical settings. Collectively, the present study illustrates integrative biological mechanisms for sensorimotor gating, underscoring the cross-disease nature of this behavioral dimension and translational utility of the findings under the era of precision medicine in brain disorders.
PTBP2-dependent alternative splicing regulates protein transport and mitochondria morphology in post-meiotic germ cells.
Authors: Hannigan Molly M , Fujioka Hisashi , Brett-Morris Adina , Mears Jason A , Licatalosi Donny D
Published: December 2018

The RNA binding protein PTBP2 (polypyrimidine tract binding protein 2) is a key regulator of tissue-specific alternative RNA splicing. In the testis, PTBP2 is expressed in meiotic and post-meiotic germ cells (spermatocytes and spermatids, respectively). In these cells, PTBP2 is required for proper alternative mRNA splicing for over 200 genes, disproportionately affecting genes encoding proteins involved in protein trafficking via transport vesicles. In this study, we used electron microscopy to test the hypothesis that protein trafficking is impaired in the absence of PTBP2, and to further investigate why spermatogenesis abruptly halts in PTBP2-deficient spermatids. Ultrastructural analysis shows that protein trafficking in spermatids is aberrant in the absence of PTBP2. Unexpectedly, we also found that mitochondria morphology and number are significantly altered in PTBP2-deficient spermatids, consistent with increased mitochondria fission. Furthermore, we show that genes with key roles in mitochondria dynamics and function are post-transcriptionally regulated by PTBP2 and in different stages of spermatogenesis. Collectively, the data provide ultrastructural evidence that alternative splicing regulation by PTBP2 during spermatogenesis is critical for proper regulation of protein trafficking and mitochondria morphology.
Evaluating the Efficiency of Primer Extension Capture as a Method to Enrich DNA Extractions,
Authors: Winters Misa , Monroe Cara , Barta Jodi Lynn , Kemp Brian M.
Published: December 2018

In this study, we sought to document the efficiency of primer extension capture (PEC) as a method to enrich DNA eluates of targeted DNA molecules and remove nontarget molecules from pools containing both. Efficiency of the method was estimated by comparing number of “copies in” to “copies out” by quantitative polymerase chain reaction. PEC retention of DNA targets ranging 109‐288 base pairs (bps) in length was 15.88–2.14% (i.e., loss of 84.12–97.86% of target molecules). Experimental modifications of the PEC method resulted in no significant improvements. However, the benefit of PEC was revealed in its ability to remove most nontarget DNA molecules (99.99%). We also discovered that many (56.69%) of the target molecules are “lost” prior to their immobilization on the streptavidin‐coated beads. These estimates of methodological efficiency are directly comparable to previous ones observed following “fishing” for DNA, an alternative method for DNA enrichment.
Initial public offering prospectus forecast errors and mandatory explanations: evidence from New Zealand
Authors: Chen Li , Hay David , Zhuang Jingyuan
Published: December 2018

This paper examines management forecast errors in initial public offering (IPO) prospectuses of New Zealand firms and subsequent management explanations for earnings forecast errors in recent years. New Zealand has several unique features and recent changes that are worthy of research, including the requirement for management to make forecasts; a requirement to explain differences between forecast and actual; and a recent change that provides the voluntary opportunity to obtain a negative assurance opinion on forecasts. Using hand‐collected IPO data between 1998 and 2014, we find that firms that include a negative assurance opinion on the prospective financial information in the prospectus have more accurate earnings and cash flow forecasts. We investigate the subsequent explanations for forecast errors, which are mandated by a financial reporting standard. We show that management tends to attribute negative and large forecast errors to external causes rather than their own actions. Our findings have implications for regulators and investors in New Zealand and other settings.
Patterns of altered regional brain glucose metabolism in borderline personality disorder and bipolar II disorder
Authors: Bøen E. , Hjørnevik T. , Hummelen B. , Elvsåshagen T. , Moberget T. , Holtedahl J. E. , Babovic A. , Hol P. K. , Karterud S. , Malt U. F.
Published: December 2018

Objective

The relationship between borderline personality disorder (BPD) and bipolar II disorder (BIP‐II) is disputed but understudied. Here, we investigated brain glucose metabolism in these patient groups and healthy control subjects (HCs).

Methods

Sixty‐five subjects, 22 BPD (19 females), 22 BIP‐II (17 females), and 21 HC (14 females), were examined using 2‐deoxy‐2[18F]‐fluoro‐d‐glucose positron‐emission tomography (PET) scanning. Only patients without reciprocal comorbidity were recruited; BPD participants without bipolar spectrum pathology; BIP‐II participants without cluster A/B personality pathology. Groups were compared pairwise. Associations with mood state and childhood trauma were analyzed.

Results

Both patient groups exhibited hypometabolism compared with HCs in insula, brainstem, and frontal white matter. Additionally, BPD patients showed hypometabolism in hypothalamus, midbrain, and striatum; BIP‐II patients in cerebellum. Uncorrected analyses showed cortical areas of higher metabolism in BIP‐II than BPD, and associations with clinical variables differed between the groups.

Conclusion

Reduced metabolism in the insula regions was shown in both disorders, suggesting shared pathophysiological mechanisms. The observed patterns of altered metabolism specific to each patient group, as well as the uncorrected results, may also suggest differential pathophysiology. However, these latter findings must be interpreted cautiously given the non‐significant corrected results in the direct comparison between the disorders.
THE LABOR MARKET CONSEQUENCES OF TEENAGE CHILDBEARING
Authors: Silles Mary A.
Published: December 2018

This paper provides estimates of the impact of an unanticipated child during adolescence on labor supply and earnings using data for women who gave birth between 1976 and 2015 drawn from 1990 and 2000 censuses and the American Community Surveys. Twins at first birth are used as an instrument to avoid the problems of fertility endogeneity. Estimates from our instrumental variable models indicate that the arrival of a second‐born twin had severe economic consequences for adolescent women over most of our data. (JEL J13, J31, J16)
How I do it: Flexible 3‐D endoscope for endoscopic submucosal dissection
Authors: Chiu Philip W. Y. , Yip Hon Chi , Xia Xian Feng , Chan Shannon M. , Ng Enders K. W. , Lau James Y. W.
Published: December 2018

Endoscopic submucosal dissection (ESD) is technically challenging as a result of a lack of depth perception. The present article investigated the 3‐D endoscope for carrying out ESD and translated the technique from bench to clinical use. In a preclinical porcine experiment, ESD using a 3‐D endoscope was compared between an experienced and a novice endoscopist. All ESD were completed without perforation. Median operative time per surface area was significantly lower for the experienced endoscopist than for the novice (197.9 s/cm2 vs 434.7 s/cm2; P = 0.05). The second part was a prospective clinical experience to evaluate use of the 3‐D endoscope for carrying out ESD. Ten patients received ESD using the 3‐D endoscope. Four patients had gastric ESD, two had duodenal ESD and four had sigmoid and rectal ESD. There were no complications, whereas ESD failed in one patient who had gastric neoplasia at anastomosis. Mean operative time was 99.4 min, and operative time per surface area resection was 391 s/cm2. The operating endoscopist did not complain of motion sickness, whereas the assistants had some dizziness upon prolonged ESD procedure. This study showed that carrying out ESD was safe and effective using a 3‐D endoscope with an excellent 3‐D view enhancing depth perception. Future study should be conducted to compare 3‐D against 2‐D endoscopes for ESD.
Depressive symptoms and cerebral microvascular disease in adults with Type 1 diabetes mellitus
Authors: Nunley K. A. , Karp J. F. , Orchard T. J. , Costacou T. , Aizenstein H. J. , Jennings J. R. , Rosano C.
Published: December 2018

Aim

To assess the prevalence of, and risk factors for, depressive symptoms, comparing a sample of middle‐aged adults with and without juvenile‐onset Type 1 diabetes mellitus, and to determine if depressive symptoms were associated with white matter hyperintensity volume among those with Type 1 diabetes.

Methods

Depressive symptoms and white matter hyperintensities were compared between adults (age range 30–65 years) with juvenile‐onset Type 1 diabetes (n=130) and adults without Type 1 diabetes (n=133). The association of Type 1 diabetes with depression was computed before and after adjustment for white matter hyperintensities. Among the Type 1 diabetes group, the primary associations of interest were between depressive symptoms (Beck Depression Inventory score ≥10) and white matter hyperintensities (n=71), hyperglycaemia and physical activity. Associations between depressive symptoms and diabetes‐related complications, cognitive impairment, smoking and self‐reported disability were examined. Analyses were controlled for education, sex, age and antidepressant use.

Results

Depressive symptoms were more prevalent among those with vs those without Type 1 diabetes (28% vs 3%; P<0.001). White matter hyperintensities explained 40% of the association of Type 1 diabetes with depressive symptoms, while Type 1 diabetes had a direct effect of 68% on depressive symptoms. Among those with Type 1 diabetes, depressive symptoms were related to white matter hyperintensity volume, a 16‐year average HbA1c ≥58 mmol/mol (7.5%), and lower physical activity levels. Associations with other characteristics were not significant.

Conclusion

These findings suggest a cerebrovascular origin for depressive symptoms in adults with Type 1 diabetes, perhaps triggered by hyperglycaemia. Future longitudinal studies should investigate whether targeting hyperglycaemia and physical inactivity alleviates depressive symptoms, possibly by slowing the development of cerebral microvascular disease, in people with Type 1 diabetes.
Comparative effectiveness and harms of long‐acting insulins for type 1 and type 2 diabetes: A systematic review and meta‐analysis
Authors: Holmes Rebecca S. , Crabtree Elizabeth , McDonagh Marian S.
Published: December 2018

Aim

To review evidence comparing benefits and harms of long‐acting insulins in patients with type 1 and 2 diabetes.

Methods

MEDLINE and two Cochrane databases were searched during February 2018. Two authors selected studies meeting inclusion criteria and assessed their quality. Comparative studies of adult or paediatric patients with diabetes treated with insulin degludec, detemir or glargine were included. Meta‐analysis was used to combine results of similar studies, and the I2 statistic calculated to assess statistical heterogeneity.

Results

Of 2534 citations reviewed, 70 studies met the inclusion criteria. No statistically significant differences in HbA1c were seen between any two insulins or formulations. Hypoglycaemia was less probable with degludec than with glargine, including nocturnal hypoglycaemia in type 1 (rate ratio 0.68, 95% CI 0.56‐0.81) and type 2 diabetes (rate ratio 0.73, 95% CI 0.65‐0.82), and severe hypoglycaemia in type 2 diabetes (relative risk 0.72, 95% CI 0.54‐0.96). Patients with type 2 diabetes had higher rates of withdrawal because of adverse events when treated with detemir compared with glargine (relative risk 2.1, 95% CI 1.4‐3.3). Adults taking detemir gained about 1 kg less body weight than those taking degludec (type 1) or glargine (type 2).

Conclusions

No differences in glycaemic control were seen between insulin degludec, detemir and glargine. Hypoglycaemia was less probable with degludec than glargine, and patients taking detemir gained less body weight than those given degludec or glargine. In type 2 diabetes, withdrawals as a result of adverse events were more probable with detemir than glargine.
Underestimated ecosystem carbon turnover time and sequestration under the steady state assumption: A perspective from long‐term data assimilation
Authors: Ge Rong , He Honglin , Ren Xiaoli , Zhang Li , Yu Guirui , Smallman T. Luke , Zhou Tao , Yu Shi‐Yong , Luo Yiqi , Xie Zongqiang , Wang Silong , Wang Huimin , Zhou Guoyi , Zhang Qibin , Wang Anzhi , Fan Zexin , Zhang Yiping , Shen Weijun , Yin Huajun , Lin Luxiang
Published: December 2018

It is critical to accurately estimate carbon (C) turnover time as it dominates the uncertainty in ecosystem C sinks and their response to future climate change. In the absence of direct observations of ecosystem C losses, C turnover times are commonly estimated under the steady state assumption (SSA), which has been applied across a large range of temporal and spatial scales including many at which the validity of the assumption is likely to be violated. However, the errors associated with improperly applying SSA to estimate C turnover time and its covariance with climate as well as ecosystem C sequestrations have yet to be fully quantified. Here, we developed a novel model‐data fusion framework and systematically analyzed the SSA‐induced biases using time‐series data collected from 10 permanent forest plots in the eastern China monsoon region. The results showed that (a) the SSA significantly underestimated mean turnover times (MTTs) by 29%, thereby leading to a 4.83‐fold underestimation of the net ecosystem productivity (NEP) in these forest ecosystems, a major C sink globally; (b) the SSA‐induced bias in MTT and NEP correlates negatively with forest age, which provides a significant caveat for applying the SSA to young‐aged ecosystems; and (c) the sensitivity of MTT to temperature and precipitation was 22% and 42% lower, respectively, under the SSA. Thus, under the expected climate change, spatiotemporal changes in MTT are likely to be underestimated, thereby resulting in large errors in the variability of predicted global NEP. With the development of observation technology and the accumulation of spatiotemporal data, we suggest estimating MTTs at the disequilibrium state via long‐term data assimilation, thereby effectively reducing the uncertainty in ecosystem C sequestration estimations and providing a better understanding of regional or global C cycle dynamics and C‐climate feedback.
Patients´ experiences and perspectives of challenges and needs related to nonmyeloablative stem cell transplantation: Involving patients in developing a targeted rehabilitation programme
Authors: Lindman Astrid , Krintel Petersen Annemette , Olesen Gitte , Handberg Charlotte
Published: December 2018

Aims and objectives

To explore patients’ experiences and perspectives of their challenges and needs regarding their return to everyday life after allogeneic nonmyeloablative haematopoietic stem cell transplantation (NMA‐HSCT).

Background

NMA‐HSCT can cure patients with malignant blood diseases, but during the following years, the majority of patients suffer from serious side effects and complications. Hence, it is a major challenge for patients treated with NMA‐HSCT to rehabilitate, maintain physical and psychosocial functioning and return to a life in restored balance.

Design

The design was qualitative using the interpretive description methodology, and the theoretical framework symbolic interactionism inspired the interview guide and analysis.

Methods

Between April to May 2017, five focus group interviews were conducted with 15 outpatients in a haematological ward in Denmark. The patients were treated with NMA‐HSCT 8–30 months prior to the interviews. The study adheres to the Consolidated Criteria for Reporting Qualitative Research guidelines.

Results

The impaired functioning was the overarching theme and seemed to be the trigger entailing rehabilitation needs related to the following main themes: realising decline, adapting to changes, the meaning of motivation and reliance on relations. These findings seemed to affect and influence the patients' struggle for a return to an everyday life like before being diagnosed or just before undergoing NMA‐HSCT.

Conclusion

This study adds to our understanding of important elements to consider when developing a targeted rehabilitation programme.

Relevance to clinical practice

Based on our findings, the rehabilitation programme should encompass: extensive variation regarding how to address the impaired functioning through individualised approaches, multimodal interventions, interventions through several months with varying intensity, an interdisciplinary team approach supporting motivation and visualisation of every progress by tangible goal setting, communication regarding hope and support, extended supportive care for patients living alone and finally increased adherence through social sessions with relatives and fellow patients.
Caring by telecare? A hermeneutic study of experiences among older adults and their family caregivers
Authors: Karlsen Cecilie , Moe Carl Erik , Haraldstad Kristin , Thygesen Elin
Published: December 2018

Aims and objectives

To obtain a deeper understanding of the persistent use of telecare for older adults and their family caregivers.

Background

Telecare is seen as part of the solution in home care services for ageing in place. Previous studies have shown that telecare is a complex intervention, and there is still a poor understanding of older adults’ and their family caregivers’ experience with the use of telecare.

Design

This study used a qualitative hermeneutic research approach.

Method

Interviews were conducted with 18 older adults and follow‐up interviews were conducted with 15 participants after 5–6 months of use. In addition, interviews were conducted with seven close family caregivers. The COREQ checklist was used.

Results

The older adults expressed increased safety, security and independence. Although some of them experienced challenges, they continued to use the services. Furthermore, the findings revealed needs that telecare could not cover. Family caregivers reported that telecare eased their concern for a time. However, they felt increased responsibility which led to ambivalent feelings between wanting to comply with the older adults’ desire to live at home and the stress and concern this caused.

Conclusion

Telecare does improve care offered by home care services. However, it must be considered in the context of assistance and other measures and be provided in response to each individual's specific needs. Family caregivers may benefit from telecare, but telecare may also add to their care burden.

Relevance to clinical practice

There is a need for increased knowledge and information about telecare and for follow‐up from home care services. Family caregivers are important for promoting sustainable use, but a support system and better cooperation with home care services is needed.