bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraperitoneal infusion of ex vivo-cultured allogeneic NK cells in recurrent ovarian carcinoma patients (a phase I study)
Authors: Hoogstad-van Evert Janneke , Bekkers Ruud , Ottevanger Nelleke , Schaap Nicolaas , Hobo Willemijn , Jansen Joop H. , Massuger Leon , Dolstra Harry
Published: January 2019

Introduction:

Recurrent ovarian carcinoma has dismal prognosis, but control of disease and prolonged survival are possible in some patients. The estimated 5-year survival is 46% for all stages of ovarian cancer, and only 28% for metastasized disease. Notably, the majority of women with ovarian cancer are diagnosed with stage III or IV disease with a high recurrence rate. As most women with relapsed or metastatic cancer will die of progressive disease, there is an urgent need for novel therapeutic strategies. The primary aim of our study is to evaluate safety and toxicity of intraperitoneal infusion of ex vivo-expanded natural killer cells (NK), generated from CD34+ umbilical cord blood (UCB) progenitor cells, with and without a preceding non-myeloablative immunosuppressive conditioning regimen in patients suffering from recurrent ovarian cancer. The secondary objectives are to compare the in vivo lifespan, expansion, and biological activity of intraperitoneally infused NK cell products with or without preparative chemotherapy, as well as evaluate effects on disease load.

Methods:

In this phase I safety trial, 12 patients who are suffering from recurrent ovarian cancer, detected by a significant rise in serum level of CA-125 on two successive time points, will be included. Prior to UCB-NK cell infusion, a laparoscopy is performed to place a catheter in the peritoneal cavity. The first cohort of three patients will receive a single intraperitoneal infusion of 1.5-3×109 UCB-NK cells, generated ex vivo from CD34+ hematopoietic progenitor cells obtained from an allogeneic UCB unit, without a preparative chemotherapy regimen. The second group of three patients will be treated with a similar dose of UCB-NK cells following a preparative four days non-myeloablative immunosuppressive conditioning regimen with cyclophosphamide and fludarabine (Cy/Flu). If no severe toxicity is seen in these 6 patients, an extension cohort of 6 patients will be included to answer the secondary objectives.

Discussion:

This study investigates the safety of a promising new cellular therapy in a group of patients with a poor prognosis. Demonstration of safety and in vivo expansion capacity of allogeneic UCB-NK cells in the absence of Cy/Flu pretreatment will provide rationale for UCB-NK cell infusion after regular second-line chemotherapy.
Medial malleolar stress fracture resulting from repetitive stress caused by lateral ankle instability
Authors: Lee Hong Seop , Lee Young Koo , Kim Hak Soo , Lee Dhong Won , Won Sung Hun , Jung Ki Jin , Kim Chang Hyun , Kim Woo Jong
Published: January 2019

Rationale:

Stress fractures are most commonly sustained in the lower extremities owing to the repetitive weight-bearing forces. They are overuse injuries that are seen often in athletes, but rare in the general population, so early diagnosis and proper treatment are important to enable athletes to return to activity. This is a rare example of successful treatment of a medial malleolar stress fracture with lateral ankle instability.

Patient concerns:

A 16-year-old athlete presented with acute-onset left ankle pain. He was a baseball pitcher who had previously sprained left ankle while training. Subsequently, the ankle pain worsened, and he had tenderness on the medial aspect of his left ankle. The symptoms were mild at rest, but increased upon walking and training. Three years previously, he had sprained his ankle several times during baseball training.

Diagnosis:

Plain standing radiographs of the left ankle showed a vertical fracture line in the medial malleolus. Computed tomography also showed the vertical fracture in the medial malleolus. Magnetic resonance imaging revealed mild bone marrow edema in the medial malleolar area and total rupture of the anterior talofibular ligament.

Interventions:

Surgery was performed under general anesthesia, and we checked the instability of his ankle using a C-arm image intensifier, and the varus talar tilt angle was increased (10.3°). The medial malleolus stress fracture was fixed using tension bend wiring, and an arthroscopic modified Broström procedure was done.

Outcomes:

Two months postoperatively, the patient started walking, and raised-heel squatting. The medial malleolar fracture was completely united at the 3 months postoperatively on plain radiography, and return to full activity was achieved by 3 months postoperatively. Then the hardware was removed 1-year after operation and both the anterior drawer and external rotation stress tests were negative.

Lessons:

Medial malleolar stress fractures are rare, so they can be overlooked. With these fractures, plain radiographs are frequently normal initially because the medial malleolus consists mainly of cancellous bone. Physicians require a high level of suspicion when taking the patient's history and doing the physical examination. Because most occur in athletes, early diagnosis and proper treatment are important for patients’ subsequent athletic performance.
Cone beam versus conventional computed tomography angiography volume measurement in partial splenic embolization
Authors: Ishikawa Toru , Imai Michitaka , Okoshi Marina , Tomiyoshi Kei , Kojima Yuichi , Horigome Ryoko , Nozawa Yujiro , Sano Tomoe , Iwanaga Akito , Honma Terasu , Yoshida Toshiaki
Published: January 2019

When performing partial splenic arterial embolization (PSE), it can be difficult to determine the embolization ratio based on 2-dimensional digital subtraction angiography (DSA) image diagnosis alone. Therefore, at our department, we conduct computed tomography (CT) imaging intraoperatively and postoperatively to determine whether the planned embolization has been achieved. In recent years, developments in interventional radiology devices have enabled diagnostic imaging using cone beam CT. Here, we investigated whether the embolization ratio could be predicted from volume measurement with cone beam CT in PSE.

We investigated correlations between volume measurement with conventional CT angiography (CTA) and volume measurement with cone beam CTA in 11 cases that underwent PSE with cone beam CT guidance (Allura Clarity FD20; Phillips, Amsterdam, The Netherlands) between December 2013 and May 2018.

The mean subject age was 65.0 ± 5.8 years (6 men, 5 women). The subjects had underlying liver disorders of hepatitis C virus infection (4 cases), nonalcoholic steatohepatitis (4 cases), and alcohol-related disease (3 cases). A positive correlation was noted between conventional CTA and cone beam CTA, with infarction rates of 61.28 ± 9.31% and 64.04 ± 9.24%, respectively. The correlation coefficient between the 2 variables was .772.

Because blood washout occurs rapidly in the spleen, contrast medium had to be continuously injected during imaging to enable dual-phase imaging with cone beam CT. However, we successfully performed imaging up to the second phase and volume measurement for the embolization ratio by inserting a catheter into the splenic artery and confirming the cone beam CT arrival time from the DSA images. The results were almost identical to those obtained from volume measurement with conventional CT based on CTA imaging. Thus, our results suggest that the splenic embolization ratio measurement obtained via cone beam CTA can be used to assess PSE treatment endpoints.
Treatment of diaphyseal pathological fractures in children with monostotic fibrous dysplasia using cortical strut allografts and internal plating
Authors: Zhang Peng , Kang Liangqi , Hu Qimiao , Xia Chenjie , Yu Huan , Wang Lei , Lian Kejian , Lin Dasheng
Published: January 2019

Children with fibrous dysplasia (FD) chronically suffer from pain, pathological fractures, and limb deformities. The most effective methods for managing the associated pathological fractures remain controversial. The purpose of this study was to evaluate the clinical results of the treatment of diaphyseal pathological fractures in children with monostotic fibrous dysplasia (MFD) using cortical strut allografts and internal plating.

We retrospectively analyzed outcomes in nine children (5 boys, 4 girls) with diaphyseal pathological fractures due to MFD, who were treated with cortical strut allografts and internal plating (6 femoral fractures and 3 humeral fractures) between July 2007 and November 2012. The median age of patients in our study was 10 years (range 6–14 years). The fracture healing time, pain, extremity function, refracture, graft resorption, and complications were recorded to evaluate treatment effects.

The median time of follow-up was 69 months (range 60–75 months). All patients had good postoperative fracture healing with a median healing time of 14 weeks (range 12–16 weeks). None experienced refracture, graft resorption, nerve injury, or limitation of extremity function or other complications. The fixation remained stable in all patients, with no evidence of loosening screws after surgery.

In pediatric patients, the described surgical approach is an effective and reliable treatment method for diaphyseal pathological fractures caused by MFD. Cortical strut allografts, which act as biological bone plates, can provide good mechanical support while increasing the rate of fracture union.
Low dose of apatinib in treating chemotherapy and EGFR-TKI refractory non-small cell lung cancer
Authors: Liu Jin , Zheng Yulong , Xu Nong
Published: January 2019

Rationale:

Lung cancer is the leading cause of cancer-associated deaths all over the world. Although the prognosis of lung cancer has improved over the past decade due to progression in surgical techniques and systematic treatments, the patients with advanced disease still suffer poor survival. There are no standard treatment strategies for patients who have failed to respond to at least 2 lines of chemotherapy in non-small cell lung cancer (NSCLC). Apatinib, one of the latest small-molecule oral anti-angiogenesis targeted agents developed first in China, has shown remarkable anti-tumor efficacy in a variety of solid tumor types.

Patient concerns:

A 72-year-old woman underwent radical resection of the left lung cancer in July 2011, but was found a recurrence of cancer after 2 years.

Diagnoses:

The histopathological examination of the resected specimen identified the lesion as lung adenocarcinoma.

Interventions:

She received gemcitabine and carboplatin regimen as adjuvant chemotherapy for 4 cycles following the surgery in August 2011. After the tumor relapsed, she received multiple lines of chemotherapy including paclitaxel, cisplatin, docetaxel, and gemcitabine from July 2013, but still suffered progressive disease in February 2017. Then apatinib alone was used to defend against the tumor at a dose of 250 mg/d orally till December 2017.

Outcomes:

The efficacy was assessed as partial response 1 month later in March 2017. And the use of apatinib was continued till the patient died of tumor progression, achieving a progression-free survival for 10 months. During the treatment with apatinib, the patient experienced hypertension of grade 1, which was well-tolerated and manageable.

Lessons:

Apatinib might be efficient and well-tolerated for patients with advanced NSCLC who have failed to respond to multi-line treatments, even at a low dose.
Diagnostic pitfalls in a cystic ectopic intrathyroidal parathyroid adenoma mimicking a nodular goiter
Authors: Chen Jianguo , Ma Zhiqiang , Yu Jianchun
Published: January 2019

Rationale:

Cystic parathyroid adenomas are rare and seldom arise in ectopically located glands which may be found within the carotid sheath, mediastinum, thymus, or thyroid grand. They cannot be detected consistently by any imaging methods. Unusual symptoms may bring about certain pitfalls and difficulties for the diagnosis of primary hyperparathyroidism (PHPT) caused by cystic parathyroid adenomas. Until now, there are no specific guidelines on the management of cystic ectopic intrathyroidal parathyroid adenoma (ETPA).

Patient concerns:

An 82-year-old male musician presented abrupt thyroid enlargement, hoarseness, and trachea compression when he was playing the clarinet. Thyroid and renal function tests were normal. Serum-free calcium and parathyroid hormone (PTH) were in high concentration. Thyroid ultrasonography (US) detected a giant and cystic nodule within right thyroid lobe, which is the very image of cystic nodular goiter. Parathyroid US was negative. The cystic nodule had a decreasing radioactive uptake of Technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI). At patient's request, the invasive fine-needle aspiration (FNA) was not conducted.

Diagnoses:

The patient was initially diagnosed as cystic nodular goiter and inconclusive PHPT.

Interventions:

Enucleation of solitary cystic intrathyroidal nodule was conducted.

Outcomes:

The cystic nodule strongly resembled a nodular goiter grossly, but it was proved cystic ETPA by histopathology. Postoperative follow-ups found that serum-free calcium and PTH decreased sharply into normal range, and hoarseness and trachea displacement were obviously improved.

Lessons:

The diagnosis of cystic ETPA is easily overlooked for its rarity. Diagnostic pitfalls, including atypical symptoms, inconclusive imaging manifestation, and unidentified gross specimen, are highlighted. They make the diagnosis of PHPT caused by cystic ETPA challenging. Patients would rather choose surgical excision directly than invasive FNA. Acute hemorrhage of the preexisting ETPA may account for the cystic degeneration.
Coronary artery spasm induced by carotid sinus stimulation during arthroscopic shoulder surgery
Authors: Chung Jinhun , Gong Hyung Youn , Park Jinsoo , Yoo Sie Hyeon , Kim Nan Seol , Jung Ho Soon , Seo Yong Han , Chun Hea Rim , Cho Ho Bum
Published: January 2019

Rationale:

Variant angina is characterized by coronary artery spasm irrespective of the presence of fixed stenotic coronary lesions. Perioperative coronary artery spasm may be induced by the supersensitivity of vascular smooth muscle cells caused by various stimuli, including stimulation of the parasympathetic nervous system.

Patient concerns:

A 57-year-old male patient was undergoing arthroscopic rotator cuff repair under combined interscalene brachial plexus block and general anesthesia in the lateral decubitus position. While compressing the right shoulder to remove residual irrigation fluid in the shoulder through the surgical site, ventricular fibrillation occurred without ST elevation.

Interventions:

The patient achieved a return of spontaneous circulation after chest compression, defibrillation, and an epinephrine infusion.

Diagnosis:

Postoperative coronary angiography showed no significant stenosis, but it did show that the right coronary artery contracted rapidly and was completely obstructed after an intravascular injection of ergonovine, and that the contracted area returned to its normal size after nitroglycerin was injected into the coronary artery. Based on these observations, the patient was diagnosed with variant angina.

Outcomes:

The patient was discharged on postoperative day 20 without any sequelae and is currently under follow-up in the Cardiology Department.

Lessons:

Surgeons should be vigilant and take relevant precautions, as compressing the shoulder to remove residual irrigation fluid during arthroscopic shoulder surgery in the lateral decubitus position may stimulate the carotid sinus and cause coronary artery spasm.
Pulmonary Embolism in Children
Authors: Navanandan Nidhya , Stein Jill , Mistry Rakesh D.
Published: January 2019

Pulmonary embolism is an uncommon but potentially life-threatening event in children. There has been increasing awareness of pulmonary embolism in children with improved survival in children with systemic disease and advancements in diagnostic modalities. However, literature regarding pulmonary embolism in children is sparse, and thus current guidelines for management of pulmonary embolism in children are extrapolated from adult literature and remain controversial. This article reviews the background and pathophysiology of venous thromboembolism, as well as current diagnostic approach and recommended management of pulmonary embolism in children.
Endometrial Endometrioid Carcinoma With Ovarian Metastasis Showing Morula-like Features in a Patient With Cowden Syndrome: A Case Report
Authors: Kuno Ikumi , Tate Keisei , Yoshida Hiroshi , Takahashi Kenta , Kato Tomoyasu
Published: January 2019

Cowden syndrome (CS) is a multiple hamartoma syndrome associated with the development of various tumors, including endometrial cancer. However, the histology of CS-associated endometrial cancer remains to be fully described. To our knowledge, this is the first report of a patient with CS having endometrial endometrioid carcinoma with ovarian metastasis demonstrating morula-like features. A 31-yr-old, nulliparous, Japanese woman presented with abnormal genital bleeding. Endometrial biopsy revealed endometrioid carcinoma with an extensive morular formation, partially resembling atypical polypoid adenomyoma (APAM). Moreover, she had a past history of bilateral breast cancer and a family history of juvenile breast cancer in her mother. Genetic testing revealed they shared the same pathogenic germline PTEN mutation. She underwent an abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node biopsy. Pathologic examination revealed endometrial endometrioid carcinoma with APAM-like histology. Furthermore, the solid components with morula-like morphology and immunophenotypes showed myometrial invasion and ovarian metastasis (FIGO stage IIIA/pT3aN0M0). The present case highlights the need for careful assessment of myometrial invasion and extrauterine spread for appropriate gynecologic treatment even if endometrial biopsy shows APAM-like histology. Moreover, characterization of CS-associated endometrial cancers is required.
Incidental Microscopic Granulosa Cell Proliferations: Tumorlet or Non-neoplastic?
Authors: Menon Preethi D. , Valente Philip , Nazarullah Alia
Published: January 2019

Microscopic granulosa cell proliferations are rare incidental findings in ovarian and extraovarian tissue, and can simulate granulosa cell tumors. We report a case of a 22-yr-old nulliparous woman with incidental microscopic granulosa cell proliferation in the wall of an endometriotic cyst. Excision of the cyst revealed extensive endometriosis and incidental microscopic nests and cords of granulosa cells measuring 1.5 mm and positive for inhibin A and calretinin. A rare Call-Exner body was noted. An extensive literature review of both ovarian and extraovarian granulosa cell proliferations were performed to determine their possible origin, variable morphologic features and differential diagnosis. Forty-seven cases were identified occurring in pregnant (26%) and nonpregnant (74%) settings. The nonpregnant cases reveal an association with endometriosis and endometrioid adenocarcinomas. Follow-up data is very limited, but no reports of subsequent granulosa cell tumors are reported. We hypothesize that possible anovulation may play a role in the development of these proliferations. Because of unknown pathogenesis and limited follow-up data being available, their clinical significance and risk of neoplasia remain unclear.
Predictors of Lifetime Suicide Attempts in Individuals With Attenuated Psychosis Syndrome
Authors: ZUSCHLAG ZACHARY D. , KORTE JEFFREY E. , HAMNER MARK
Published: January 2019

Background:

A strong association has been shown to exist between schizophrenia and suicide; however, research examining suicidality in the prodromal phase of psychotic disorders is limited. This study aimed to meet this need by examining potential risk factors for lifetime suicide attempts in a population of individuals with attenuated psychosis syndrome (APS), as defined in the fifth edition of theDiagnostic and Statistical Manual for Mental Disordersas a condition for further study.

Methods:

A retrospective chart review was conducted to identify individuals with APS during a 5-year period across a large medical university’s inpatient and outpatient settings. Sociodemographic and clinical factors were examined in relation to suicide attempts to identify risk factors for suicide attempts. χ2analyses were used to analyze dichotomous variables, andttest analyses were used to compare means of continuous predictors among those with versus without suicide attempts. Final analyses consisted of fitting multivariate logistic regression models to control for sociodemographic factors.

Results:

In total, 26.3% of the APS population had at least 1 lifetime suicide attempt. Six covariates were found to be statistically significant predictors of suicide attempts: Axis II disorders (P=0.006); history of trauma as a whole (P=0.022); the subcategory of sexual trauma (P=0.005); tobacco use (P=0.039); family history of nonpsychotic Axis I disorders (P=0.042); and number of hospitalizations (P=0.001).

Conclusions:

Suicidality is a prominent feature of APS, and a number of risk factors increase the likelihood of suicide attempts in this population.
Complex PTSD in ICD-11: A Case Report on a New Diagnosis
Authors: ROSENFIELD PAUL J. , STRATYNER ALEXANDRA , TUFEKCIOGLU SUMRU , KARABELL SUSAN , MCKELVEY JENNIFER , LITT LISA
Published: January 2019

The World Health Organization (WHO) has included complex post-traumatic stress disorder (C-PTSD) in the final draft of the 11th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), which was published in June, 2018 and is scheduled to be submitted to WHO’s World Health Assembly for official endorsement in 2019. Mental health providers will want to be informed about this diagnosis in order to provide effective treatment. Complex PTSD, or developmental PTSD as it is also called, refers to the constellation of symptoms that may result from prolonged, chronic exposure to traumatic experiences, especially in childhood, as opposed to PTSD which is more typically associated with a discrete traumatic incident or set of traumatic events. Although it has been a controversial diagnosis and is not included in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), lines of evidence support its distinct profile and utility. In this case study, we elucidate and discuss some aspects of the diagnosis and its treatment.
Emerging Psychotherapies for Psychosis
Authors: KNAUSS DANIEL , RIDENOUR JEREMY , HAMM JAY A.
Published: January 2019

Recent developments in the research and clinical literatures have highlighted the importance of focusing on higher-order cognitive processes in the treatment of psychotic disorders. A particular emphasis has been placed on how impairments in self-monitoring and the ability to form mental representations of others uniquely manifest in psychosis. At the same time, the recovery movement has influenced clinical innovations by emphasizing the importance of subjective domains of recovery that privilege the individual’s phenomenological experience. In this column, we outline 2 emerging approaches to the treatment of psychosis, Metacognitive Reflection and Insight Therapy and Mentalization-based Therapy for Psychosis, highlighting the ways that each approach targets higher-order cognitive processes as a focused point of intervention, while maintaining a collaborative treatment approach that values the patient’s agency.
The Potential Perils of a Suicide-specific Diagnosis
Authors: WORTZEL HAL S. , NAZEM SARRA , BAHRAINI NAZANIN H. , MATARAZZO BRIDGET B. , SILVERMAN MORTON M.
Published: January 2019

The clinical and scientific challenges inherent in treating and investigating suicide warrant novel approaches to this public health issue of paramount importance. The implementation of suicide-specific diagnoses has been proposed as one possible way to address this problem and was described in the first column of this special 2-part series. This second column explores potential unintended consequences related to such proposed diagnoses and alternative solutions that might afford greater benefits. The idea of suicide-specific diagnoses represents a novel approach, and one worthy of further discussion and consideration; the debate featured in this series represents a joint effort to advance the dialogue about suicide and to promote innovation.
Type A Aortic Dissection Complicated by Renal and Lower Extremity Malperfusion
Authors: Gargotta Hillary R.
Published: January 2019

Acute aortic dissection is a life-threatening condition with the potential for serious complications such as myocardial infarction, heart failure, stroke, paraplegia, renal failure, mesenteric ischemia, and limb ischemia. Emergency department clinicians must be aware of the potential ischemic complications of aortic dissection and act quickly to prevent irreversible organ damage and death. This article highlights a case of a 49-year-old man who developed renal and lower extremity malperfusion secondary to Stanford Type A aortic dissection. Important historical clues and objective findings characteristic of acute aortic dissection and end-organ ischemia are discussed with the purpose of increasing reader knowledge of aortic dissection and signs of organ malperfusion with the hope that better awareness results in improved patient outcomes.
Exploring Emergency Department Provider Experiences With and Perceptions of Weight-Based Versus Individualized Vaso-Occlusive Treatment Protocols in Sickle Cell Disease
Authors: Knight La'Kita M. J. , Onsomu Elijah O. , Bosworth Hayden B. , Crawford Regina D. , DeMartino Theresa , Glassberg Jeffrey , Paice Judith A. , Miller Christopher N. , Richardson Lynne , Tanabe Paula
Published: January 2019

Treatment of vaso-occlusive episodes (VOEs) is the most common reason for emergency department (ED) treatment of sickle cell disease (SCD). We (1) compared perceptions of the usability and ability to manage VOE pain between ED nurses and other ED provider types, ED sites, and VOE protocols (individualized vs. weight-based), and (2) identified ED nurse and other provider protocol suggestions. A secondary analysis of provider survey data collected immediately after caring for a patient enrolled in a randomized controlled trial comparing weight-based versus individualized opioid dosing for VOE. Research staff asked the ED nurses and other ED providers (nurse practitioners [NPs], physician assistants [PAs], residents, and attending physicians) 5 questions related to the protocol's ease of use and ability to manage pain. There were 236 surveys completed. Attending physicians (n = 15), residents (n = 88), PAs (n = 21), and NPs (n = l) were more satisfied than nurses (n = 111) with the clarity of the analgesic ordering (97.6% vs. 0%, p = 0.0001) and ability to manage the patient's VOE pain (91% vs. 0%, p = 0.0001). When comparing both protocols with the usual ED strategy in their ED to manage VOE, more nurses than other ED providers perceived the study patients' pain management protocol as better (100% vs. 35.2%, p = 0.0001). Other ED providers perceived the individualized versus weight-based protocol as better at managing pain than their usual ED strategy (70.3% vs. 59.5%, p = 0.04). The individualized protocol was perceived as better in managing VOE than the weight-based ED strategy. While physicians were satisfied with the clarity of the protocols, nurses were not. Improved protocol usability is required for widespread ED implementation.
Inoculum size effects in blaIMP-6 and plasmid-mediated quinolone resistance gene-positive Enterobacteriaceae in Japan
Authors: Ogawa Yoshihiko , Nakano Ryuichi , Kasahara Kei , Mizuno Tomoki , Hirai Nobuyasu , Nakano Akiyo , Suzuki Yuki , Kakuta Naoki , Masui Takashi , Yano Hisakazu , Mikasa Keiichi
Published: January 2019

The aim of this study was to examine the resistance genes in clinical isolates which produced IMP-6 type metallo-β-lactamase lactamase (MBL) and had mildly reduced susceptibilities to levofloxacin and/or amikacin. The inoculum size effect was also assessed. A total of 14 Enterobacteriaceae isolates (2 Escherichia coli and 12 Klebsiella pneumoniae) which produced IMP-6 MBL, and had mild increases in their MICs for levofloxacin and amikacin were examined. Thirteen out of 14 isolates harbored CTX-M-2, with the remaining isolate co-harboring CTX-M-2 and CTX-M-1 as ESBLs. All isolates carried one or more PMQRs; aac(6′)-Ib-cr was the most prevalent (92.8%), followed by oqxA (64.3%), qnrS (42.9%), oqxAB (21.4%), and qnrB (14.3%). The inoculum size effects were significant in all strains for meropenem, 13 for imipenem, 7 for levofloxacin, and 3 for amikacin. Conjugation was successfully performed with 8 isolates and 11 strains were obtained. Eleven of the experimental strains (100%), and 8 strains (72.7%) showed inoculum size effects for meropenem and imipenem, respectively. No inoculum size effect was seen for levofloxacin. Four strains harbored qnr genes and 2 strains harbored qnr genes and QRDR mutations concurrently. blaIMP-6 positive Enterobacteriaceae with mildly reduced susceptibilities to levofloxacin and/or amikacin also harbored at least one plasmid-mediated drug resistance gene. These represent an unrecognized threat, capable of compromising the in vitro activity of many classes of antimicrobial agents. We conclude that IMP-6 MBL plays an important role in decreasing the MIC for carbapenems, whereas qnr does not for levofloxacin.
Implication of HisF fromAcinetobacter baumanniiin persistence during a pneumonia infection
Authors: Martínez-Guitián Marta , Vázquez-Ucha Juan C. , Álvarez-Fraga Laura , Conde-Pérez Kelly , Vallejo Juan A. , Bou Germán , Poza Margarita , Beceiro Alejandro
Published: January 2019

ThehisFgene fromA. baumanniiATCC 17978 was found over-expressed during a murine pneumonia infection. A mutant strain lackinghisFshowed its involvement in virulence during mice pneumonia as well as in host inflammatory response, where the product of HisF may act as negative regulator in the production of pro-inflammatory cytokines. This work evaluates the role of HisF in theA. baumanniipathogenesis and suggests its potential as a new target for antimicrobial therapies.
Effect of nitrite on neural activity in the healthy brain
Authors: Franko Edit , Ezra Martyn , Crockett Douglas C , Joly Olivier , Pattinson Kyle
Published: January 2019

Background

Nitrite is a major intravascular store for nitric oxide. The conversion of nitrite to the active nitric oxide occurs mainly under hypoxic conditions to increase blood flow where it is needed the most. The use of nitrite is, therefore, being evaluated widely to reduce the brain injury in conditions resulting in cerebral hypoxia, such as cardiac arrest, ischaemic stroke or subarachnoid haemorrhage. However, as it is still unknown how exogenous nitrite affects the brain activity of healthy individuals, it is difficult to clearly understand how it affects the ischaemic brain.

Objective

Here we performed a double-blind placebo-controlled crossover study to investigate the effects of nitrite on neural activity in the healthy brain.

Methods

Twenty-one healthy volunteers were recruited into the study. All participants received a continuous infusion of sodium nitrite (0.6mg/kg/h) on one occasion and placebo (sodium chloride) on another occasion. Electroencephalogram was recorded before the start and during the infusion. We computed the power spectrum density within the conventional frequency bands (delta, theta, alpha, beta), and the ratio of the power within the alpha and delta bands. We also measured peripheral cardiorespiratory physiology and cerebral blood flow.

Results

We found no significant effect of nitrite on the power spectrum density in any frequency band. Similarly, the alpha-delta power ratio did not differ between the two conditions. However, nitrite infusion decreased the mean blood pressure and increased the methaemoglobin concentration in the blood.

Conclusion

Our study shows that exogenous sodium nitrite does not alter the electrical activity in the healthy brain. This might be because the sodium nitrite is converted to vasoactive nitric oxide in areas of hypoxia, and in the healthy brain there is no significant amount of conversion due to lack of hypoxia. However, this lack of change in the power spectrum density in healthy people emphasises the specificity of the brain’s response to nitrite in disease.
Sex differences in age- and performance-related patterns of brain activity during episodic encoding and retrieval of spatial contextual details
Authors: Subramaniapillai Sivaniya , Rajagopal Sricharana , Elshiekh Abdelhalim , Pasvanis Stamatoula , Ankudowich Elizabeth , Rajah M. Natasha
Published: January 2019

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. In the current task fMRI study, we tested the hypothesis that there are sex differences in the effect of age and memory performance on brain activity during episodic encoding and retrieval of face-location associations (spatial context memory). Forty-one women and 41 men between the ages of 21 to 76 years participated in this study. Between-group multivariate partial least squares (PLS) analysis of the fMRI data was conducted to directly test for sex-group differences and similarities in age-related and performance-related patterns of brain activity. Our behavioural analysis indicated no significant sex differences in retrieval accuracy on the fMRI tasks. In relation to performance effects, we observed similarities and differences in how retrieval accuracy related to brain activity in women and men. Both sexes activated dorsal and lateral prefrontal cortex (PFC), inferior parietal cortex (IPC) and left parahippocampal gyrus (PHG) at encoding and this supported subsequent memory performance. However, there were sex differences in retrieval activity in these same regions and in lateral occipital-temporal and ventrolateral PFC. In relation to age effects, we observed sex differences in the effect of age on memory-related activity within PFC, IPC, PHG and lateral occipital-temporal cortices. Overall, our findings suggest that the neural correlates of age-related spatial context memory decline differ in women compared to men.
Age- and reserve-related increases in fronto-parietal and anterior hippocampal activity during episodic encoding predict subsequent memory
Authors: Elshiekh Abdelhalim , Subramaniapillai Sivaniya , Rajagopal Sricharana , Pasvanis Stamatoula , Ankudowich Elizabeth , Rajah M. Natasha
Published: January 2019

Remembering associations between encoded items and their contextual setting is a feature of episodic memory. Although this ability deteriorates with age in general, there is substantial variability in how older individuals perform on episodic memory tasks. This variability may stem from genetic and/or environmental factors related to reserve, allowing some individuals to compensate for age-related decline through differential recruitment of brain regions. In this fMRI study, we tested predictions related to reserve and compensation in a large adult lifespan sample (N=154). We used multivariate Behaviour Partial Least Squares (B-PLS) analysis to examine how age, retrieval accuracy, and a proxy measure of reserve, impacted brain activity patterns during spatial and temporal context encoding and retrieval. Reserve modulated age-related compensatory brain responses in ventral visual, temporal, and fronto-parietal regions during memory encoding as a function of task demands. Activity in inferior parietal, medial temporal, and ventral visual regions were strongly impacted by age at encoding and retrieval, but were also related to individual differences in reserve. Our findings are consistent with the concepts of reserve and compensation and suggest that reserve may mitigate age-related decline by modulating compensatory brain responses in the aging brain.
Retrovirus insertion site analysis of LGL leukemia patient genomes
Authors: Li Weiling , Yang Lei , Harris Robert S. , Lin Lin , Olson Thomas L. , Hamele Cait E. , Feith David J. , Loughran Thomas P. , Poss Mary
Published: January 2019

Background

Large granular lymphocyte (LGL) leukemia is an uncommon cancer characterized by a sustained clonal proliferation of LGL cells. Antibodies reactive to retroviruses have been documented in the serum of patients with LGL leukemia. Culture or molecular approaches have to date not been successful in identifying a retrovirus.

Methods

Because a retrovirus must integrate into the genome of an infected cell, we focused our efforts on detecting a novel retrovirus integration site in the clonally expanded LGL cells. We present a new computational tool that uses long-insert mate pair sequence data to search the genome of LGL leukemia cells for retrovirus integration sites. We also utilize recently published methods to interrogate the status of polymorphic human endogenous retrovirus type K (HERV-K) provirus in patient genomes.

Results

While our analysis did not reveal any new retrovirus insertions in LGL genomes from LGL leukemia patients, we did identify four HERV-K provirus integration sites that are polymorphic in the human population and absent from the human reference genome, hg19. To determine if the prevalence of these or other polymorphic proviral HERV-Ks differed between LGL leukemia patients and the general population, we applied a recently developed approach that reports all sites in the human genome occupied by a proviral HERV-K. Using the 1000 genomes project (KGP) data as a reference database for HERV-K proviral prevalence at each polymorphic site, we show that there are significant differences in the number of polymorphic HERV-Ks in the genomes of LGL leukemia patients of European origin compared to individuals with European ancestry in the KGP data.

Conclusions

Our study confirms that the integration of a new infectious or endogenous retrovirus does not cause the clonal expansion of LGL cells in LGL leukemia, although we do not rule out that these cells could be responding to retroviral antigens produced in other cell types. However, it is of interest that the burden of polymorphic proviral HERV-K is elevated in LGL leukemia patient genomes. Our research emphasizes the merits of comprehensive genomic assessment of HERV-K in cancer samples and suggests that further analyses to determine contributions of HERV-K to LGL leukemia are warranted.
Temperament profile and its association with the vulnerability to smartphone addiction of medical students in Indonesia
Authors: Hanafi Enjeline , Siste Kristiana , Wiguna Tjhin , Kusumadewi Irmia , Nasrun Martina Wiwie
Published: January 2019

Temperament profiles of an individual with high novelty seeking and low harm avoidance have been reported to be related to substance addiction, but smartphone addiction could be different from substance addiction. Medical students have high exposure to smartphone use. Screening their risk of smartphone addiction based on the temperament profile may help in deciding best prevention approach. This research aimed to examine the temperament profile and its association with vulnerability to smartphone addiction of medical students in Jakarta, Indonesia. The research was conducted with cross sectional design and simple random sampling. The Temperament and Character Inventory and the Smartphone Addiction Scale were used to measure desired outcomes. Logistic regression analysis was performed to identify the relationship between demographic factors, pattern of smartphone use, temperament type, and vulnerability to smartphone addiction. Of the 185 samples, most subjects have low novelty seeking, high reward dependence, and high harm avoidance. The average smartphone usage in a day was 7.94 hours (SD 3.92) with the initial age of smartphone usage was 7.58 years (SD 2.43). The respondents used smartphone for communication and accessing social media. High harm avoidance temperament was significantly associated with risk of smartphone addiction with OR 2.035; 95% CI 1.119 to 3.701). This study shows that smartphone addiction has similarities with other behavior addictions. Harm avoidance temperament is associated with the risk of smartphone addiction. Screening on risk of smartphone addiction based on temperament type should be done on medical students.
Crystal structure of the co-crystal salt 2-amino-6-bromopyridinium 2,3,5,6-tetrafluorobenzoate
Authors: Bosch Eric
Published: January 2019

The asymmetric unit of the co-crystal salt 2-amino-6-bromopyridinium 2,3,5,6-tetrafluorobenzoate, C5H6BrN2
+·C7HF4O2
−, contains one pyridinium cation and one benzoate anion. In the crystal, the aminopyridinium cationic unit forms two hydrogen bonds to the benzoate oxygen atoms in an R
2
2(8) motif. Two pyridinium benzoate units are hydrogen bonded through self-complementary hydrogen bonds between the second amine hydrogen and a carboxylate O with a second R
2
2(8) motif to form a discrete hydrogen-bonded complex containing two 2-amino-6-bromopyridinium moieties and two 2,3,5,6-tetrafluorobenzoate moieties. The 2-amino-6-bromopyridinium moieties π-stack in a head-to-tail mode with a centroid–centroid separation of 3.7227 (12) Å and adjacent tetrafluorobenzoates also π-stack in a head-to-tail mode with a centroid–centroid separation of 3.6537 (13) Å.
Crystal structure of bromidopentakis(tetrahydrofuran-κO)magnesium bis[1,2-bis(diphenylphosphanyl)benzene-κ2
P,P′]cobaltate(−1) tetrahydrofuran disolvate
Authors: Girigiri Patience B. , Carpenter Stephanie H. , Brennessel William W. , Neidig Michael L.
Published: January 2019

Structural characterization of the ionic title complex, [MgBr(THF)5][Co(dpbz)2]·2THF [THF is tetrahydrofuran, C4H8O; dpbz is 1,2-bis(diphenylphosphanyl)benzene, C30H24P2], revealed a well-separated cation and anion co-crystallized with two THF solvent molecules that interact with the cation via weak C—H...O contacts. The geometry about the cobalt center is pseudotetrahedral, as is expected for a d
10 metal center, only deviating from an ideal tetrahedral geometry because of the restrictive bite angles of the bidentate phosphane ligands. Three THF ligands of the cation and one co-crystallized THF solvent molecule are each disordered over two orientations. In the extended structure, the cations and THF solvent molecules are arranged in (100) sheets that alternate with layers of anions, the latter of which show various π-interactions, which may explain the particular packing arrangement.
On researching activity tracking to support learning: a retrospective
Authors: Lee Victor R.
Published: January 2019

Purpose

This paper aims to discuss research and design of learning activities involving activity tracking and wearable activity tracking technology.

Design/methodology/approach

Three studies are summarized as part of a program of research that sought to design new learning activities for classroom settings. The first used data from a qualitative interview study of adult athletes who self-track. The second used video excerpts from a designed learning activity with a group of fifth grade elementary students. The third study draws largely on quantitative assessment data from an activity tracking unit enactment in a rural sixth grade class.

Findings

Activity tracking appears to provide opportunities for establishing benchmarks and calibration opportunities related to intensity of physical activities. Those features of activity tracking can be leveraged to develop learning activities where elementary students discover features of data and how data are affected by different distributions. Students can show significant improvement related to statistical reasoning in classroom instructional units that centralize the use of self-tracked data.

Originality/value

As activity tracking is becoming a more ubiquitous practice with increased pervasiveness and familiarity with mobile and wearable technologies, this paper demonstrates a topical intersection between the information and learning sciences, illustrates how self-tracking can be recruited for instructional settings, and it discusses concerns that have emerged in the past several years as the technology related to activity tracking begins to be used for educational purposes.
Refining a clinical practice framework to engage clients with brain injury in goal setting
Authors: Prescott Sarah , Fleming Jennifer , Doig Emmah
Published: January 2019

Background/aim

Client‐centred goal setting is fundamental to occupational therapy practice and has been increasingly embraced by all rehabilitation practioners. Goal setting in clinical practice is a highly individualised process and may be more challenging with people with acquired brain injury. However, research examining practice is limited. We developed the Client‐Centred Goal Setting Practice Framework to explain how client‐centred goals are developed in brain injury rehabilitation. This framework was based on interview data and may reflect practitioner's theoretical knowledge rather than goal setting processes used in routine practice. The aims of this study were to explore the application of the framework to every‐day practice, examine the extent to which goal setting was client‐centred and refine the framework.

Methods

A mixed methods approach was employed. Participants were community dwelling clients with ABI and their practitioners, drawn from a hospital outpatient service and community private practices. The communication exchange between practitioners and clients during routine goal setting was audio‐recorded, transcribed verbatim and analysed using framework analysis. Quantitative measures evaluated the client‐centredness of goals.

Results

A total of 65 goal setting sessions with 36 clients and 17 practitioners (n = 8 occupational therapists) were analysed. The three goal setting phases of the framework and associated processes and strategies were represented. The ‘establishing trust’ process was interwoven throughout all phases and an additional strategy, ‘social connection’ was identified.

Conclusion

The framework provides preliminary evidence about the core processes and strategies which uses establishing trust to engage clients with ABI in goal setting, and may be a useful tool to guide client‐centred goal setting practice in similar services.
Continued misuse of multiple testing correction methods in population genetics‐A wake‐up call?
Authors: Sethuraman Arun , Gonzalez Nicolette M. , Grenier Christy E. , Kansagra Khyati S. , Mey Ken K. , Nunez‐Zavala Stefany B. , Summerhays Bryce E. W. , Wulf Gwendalyn K.
Published: January 2019

Population geneticists often use multiple independent hypothesis tests of Hardy–Weinberg Equilibrium (HWE), Linkage Disequilibrium (LD), and population differentiation, to make broad inferences about their systems of choice. However, correcting for Family‐Wise Error Rates (FWER) that are inflated due to multiple comparisons, is sparingly reported in our current literature. In this issue of Molecular Ecology Resources, perform a meta‐analysis of 215 population genetics studies published between 2011 and 2013 to show (i) scarce use of FWER corrections across all three classes of tests, and (ii) when used, inconsistent application of correction methods with a clear bias towards less‐conservative corrections for tests of population differentiation, than for tests of HWE, and LD. Here we replicate this meta‐analysis using 205 population genetics studies published between 2013 and 2018, to show the same continued disuse, and inconsistencies. We hope that both studies serve as a wake‐up call to population geneticists, reviewers, and editors to be rigorous about consistently correcting for FWER inflation.