bluuebunny/crossref_metadata_2025 huggingface dataset:
Reading Ngũgĩ Reading Conrad
Authors: Wollaeger Mark
Published: December 2018

This chapter considers points of intersection between Ngũgĩ wa Thiong’o and Joseph Conrad. By Ngũgĩ’s own account, his rewriting of Conrad’s Under Western Eyes (1911) as A Grain of Wheat (1967) triggered a crisis of audience that ultimately led him to abandon English for his native Gikuyu. To further complicate the question of influence, Wollaeger also examines the relationship between two works of nonfiction: Conrad’s A Personal Record (1912) and Ngũgĩ’s Decolonizing the Mind (1986). At the heart of Ngũgĩ’s attempt to fashion premodern tribalism into a utopian space are two problems that still animate critical discussion. What is the status of the local and the indigenous? Does attention to influence reinstate a center-periphery model in postcolonial criticism? This chapter shows the extent to which Conrad and Ngũgĩ both anticipate and generate theoretical models later used to articulate modernism and postcolonialism as fields of inquiry.
Make It New
Authors: Bahri Deepika
Published: December 2018

In considering Arundhati Roy’s The God of Small Things (1997), the author observes that time is a central preoccupation in the novel. But how does postcolonialism situate itself in relation to a temporality whose structure, logic, and rhythm have been defined by the West and the experience of colonization? Roy responds to this problem by examining the figure of the Kathakali man, a native storyteller who uses dance, movement, and costume to relate stories derived from the Indian epics, the Mahabharata and Ramayana. Like the stories of the Kathakali man, Roy’s own narrative is disjunctive and recursive, generating a temporal scheme that is at once static and dynamic. Such a handling of time enables Roy to construct what the author calls a “postcolonial modernism,” which employs the formal devices of modernism to arrive at a more genuinely postcolonial engagement with the past and its historical traumas.
An image reconstruction method for an X-ray telescope system with an angular resolution booster
Authors: Morii Mikio , Ikeda Shiro , Maeda Yoshitomo
Published: December 2018

We propose an image reconstruction method for an X-ray telescope system with an angular resolution booster proposed by Maeda et al. (2018, PASJ, submitted). The system consists of double multi-grid masks in front of an X-ray mirror and an off-focused two-dimensional imager. Because the obtained image is off-focused, an additional image reconstruction process is assumed to be included. Our image reconstruction method is an extension of the traditional Richardson–Lucy algorithm with two regularization terms, one for sparseness and the other for smoothness. Such a combination is desirable for astronomical imaging because astronomical objects have a variety in shape, from point sources to diffuse sources to mixtures of both. The performance of the system is demonstrated with simulated data for point sources and diffuse X-ray sources such as Cas A and the Crab Nebula. The image resolution is improved from a few arcmin of focused image without the booster to a few arcsec with the booster. Through the demonstration, the angular resolution booster with the image reconstruction method is shown to be feasible.
Current Available Cellular and Tissue-Based Products for Treatment of Skin Defects
Authors: Liu Yukun , Panayi Adriana C. , Bayer Lauren R. , Orgill Dennis P.
Published: December 2018

The occurrence of diabetic foot ulcers and venous leg ulcers is increasing because of aging population trends as well as increases in the number of people with diabetes and obesity. New technologies have been developed to treat these conditions, whereas other technologies previously designed for burns and traumatic wounds have been adapted. This article reviews the development of selected skin replacement technologies, particularly cellular and tissue-based products, highlighting their effectiveness on diabetic foot ulcers, venous leg ulcers, and burns.
31st Annual APRN Legislative Update
Authors: Phillips Susanne J.
Published: December 2018

The Annual Legislative Update describes recent legislative and regulatory changes to practice, reimbursement, and prescriptive authority that have the most impact on NPs and other advanced practice registered nurses across the country.
Opioid and Cannabis Co-Use among Adults With Chronic Pain: Relations to Substance Misuse, Mental Health, and Pain Experience
Authors: Rogers Andrew H. , Bakhshaie Jafar , Buckner Julia D. , Orr Michael F. , Paulus Daniel J. , Ditre Joseph W. , Zvolensky Michael J.
Published: December 2018

Objectives:

Opioid misuse constitutes a significant public health problem and is associated with a host of negative outcomes. Despite efforts to curb this increasing epidemic, opioids remain the most widely prescribed class of medications. Prescription opioids are often used to treat chronic pain despite the risks associated with use, and chronic pain remains an important factor in understanding this epidemic. Cannabis is another substance that has recently garnered attention in the chronic pain literature, as increasing numbers of individuals use cannabis to manage chronic pain. Importantly, the co-use of substances generally is associated with poorer outcomes than single substance use, yet little work has examined the impact of opioid-cannabis co-use.

Methods:

The current study examined the use of opioids alone, compared to use of opioid and cannabis co-use, among adults (n = 450) with chronic pain on mental health, pain, and substance use outcomes.

Results:

Results suggest that, compared to opioid use alone, opioid and cannabis co-use was associated with elevated anxiety and depression symptoms, as well as tobacco, alcohol, cocaine, and sedative use problems, but not pain experience.

Conclusions:

These findings highlight a vulnerable population of polysubstance users with chronic pain, and indicates the need for more comprehensive assessment and treatment of chronic pain.
Medium- to Long-term Follow-up of Obstetric Anal Sphincter Injury
Authors: Turel Friyan D. , Langer Susan , Shek Ka Lai , Dietz Hans Peter
Published: December 2018

BACKGROUND:

Obstetric anal sphincter injury is the primary modifiable risk factor for anal incontinence in women. Currently, endoanal ultrasound is most commonly used to detect residual anal sphincter defects after childbirth. Translabial ultrasound has recently been introduced as a noninvasive alternative.

OBJECTIVES:

This study aimed to determine medium- to long-term outcomes in women after obstetric anal sphincter injuries diagnosed and repaired at delivery.

DESIGN:

This is a cross-sectional study.

SETTINGS:

This study was performed in a tertiary obstetric unit.

PATIENTS:

Between 2005 and 2015, 707 women were diagnosed with obstetric anal sphincter injuries; 146 followed an invitation for follow-up.

INTERVENTIONS:

Clinical examination, anal manometry, and translabial ultrasound were performed.

MAIN OUTCOME MEASURES:

The primary outcomes measured were the St Mark incontinence score and the evidence of sphincter disruption on translabial ultrasound.

RESULTS:

Of 372 contactable patients, 146 attended at a mean follow-up of 6.6 years (1.7–11.9), of which 75 (51%) reported symptoms of anal incontinence with a median “bother score” of 6 (interquartile range, 3–8). Median St Mark score was 3 (interquartile range, 2–5). Twenty-four (16%) had a score of ≥5. Women who had been diagnosed with a 3c/4th degree tear had more symptoms (58% vs 44%), significantly lower mean maximal resting pressure (p< 0.001), maximal squeeze pressure (p< 0.001), and more residual external (p< 0.001) and internal (p= 0.012) sphincter defects in comparison with those who had a 3a/3b tear. Women with residual external sphincter defects had lower mean maximal squeeze pressure (p= 0.02). Residual internal sphincter defects (p= 0.001) and levator avulsion (p= 0.048) are independent risk factors for anal incontinence on multivariate modeling.

LIMITATIONS:

This study was limited by the lack of predelivery data of bowel symptoms and BMI and incomplete intrapartum documentation of tear grade.

CONCLUSIONS:

Symptoms of anal incontinence were highly prevalent (51%), with a high bother score of 6. St Mark scores were associated with residual internal anal sphincter defects and levator avulsion. Women who had a higher tear grade showed a higher incidence of residual sphincter defects and lower manometry pressures. SeeVideo Abstractat http://links.lww.com/DCR/A824.
Rhinocerebral mucormycosis after functional endoscopic sinus surgery
Authors: Yeo Cha Dong , Kim Jong Seung , Kwon Sam Hyun , Lee Eun Jung , Lee Min Hee , Kim Su Geun , You Yeon Seok , Kim June Sun , Lee Jong Hwan , Ryu Ji Seob
Published: December 2018

Rationale:

Mucormycosis is a rare fungal infection which mainly develops in compromised hosts and the associated mortality rate is high.

Patient concerns:

We report a case of mucormycosis in a 59-year-old woman following routine endoscopic sinus surgery. The patient had a history of diabetes mellitus (DM) and bronchial asthma.

Diagnoses:

On follow-up 4 weeks after the first functional endoscopic sinus surgery (FESS), she complained of a severe headache and was readmitted for a second period. Endoscopic examination revealed bony erosion and a whitish discharge on the left middle turbinate, which was confirmed as mucormycosis by endoscopic biopsy.

Interventions:

Endoscopic debridement of the necrotic tissue and middle turbinectomy were performed and the patient was treated with intravenous amphotericin B for 3 months (3.5 mg/kg/day).

Outcomes:

About 1 month into the second period of hospitalization, left Bell's palsy had occurred. The facial palsy improved naturally after 2 months of hospitalization. One year after endoscopic debridement, follow-up endoscopy showed that there was no residual lesion.

Conclusion:

This is the first report of mucormycosis after routine endoscopic sinus surgery. We did not miss headache symptom after FESS surgery, and diagnosed mucormycosis through early endoscopic biopsy, which played an important role in curing the patient. In addition to the importance of medical therapy such as DM control for patients, emotional support and psychiatric treatment are also important factors as these patients require hospitalization for a long period, 3 months in the case of this patient.
Efficacy of risedronate in improving bone mineral density in patients undergoing total hip arthroplasty
Authors: Su Jing , Wei Yi , Li Xiao Ming , Diao Yan-Ping , Liu Huai-Gang , Zhang Liang
Published: December 2018

Background:

Risedronate is widely used in the therapy of osteoporosis and other metabolic bone diseases. This meta-analysis was aimed to assess whether administration risedronate could increase the bone mineral density (BMD) in patients undergoing primary total hip arthroplasty (THA).

Methods:

Electronic databases: PubMed, EMBASE, Web of Science, Cochrane Library, and Chinese Wanfang database were searched for all relevant studies. Inclusion criterion was that patients prepared for THA and use risedronate as intervention group and placebo as control group. BMD change in Gruen zone 1 and 7 were primary outcomes. Meta-analysis was performed using Stata 12.0 software.

Results:

Six RCTs were finally included in this meta-analysis. Compared with control group, risedronate has a beneficial role in increasing BMD in Gruzen 1, 2 6, and 7 at 3 months (P < .05). Oral risedronate has a beneficial role in preservation of BMD in all of the Gruen zones at 6 and 12 months (P < .05). Moreover, oral risedronate could significantly increase the Harris hip scores and bone alkaline phosphatase than control group (P < .05).

Conclusion:

Oral risedronate has an effect on the preservation of periprosthetic BMD in proximal regions (Gruen zone 1, 2, 3, and 7) at 3 months and all of the regions at 6 and 12 months after THA.
Transurethral procedures in the treatment of benign prostatic hyperplasia
Authors: Sun Feng , Sun Xincheng , Shi Qinglu , Zhai Yuzhang
Published: December 2018

Background:

With the progress of surgical techniques and instruments, various minimally invasive surgical therapies were developed to treat benign prostatic hyperplasisa (BPH). However, the efficacy and safety of different transurethral procedures for the treatment of BPH are still undefined.

Method:

A systematic search was performed for all randomized controlled trials (RCTs), which compared the transurethral procedures for BPH from 1995 to 2016. The clinical baseline characteristics, International Prostate Symptom Score (IPSS), quality of life (QoL), postvoid residual (PVR), maximum flow rate (Qmax), short-term and long-term complications were analyzed using RevMan and ADDIS software.

Result:

Eighty-eight randomly controlled trials and fifteen procedures were included in the network meta-analysis. HoLEP greatly inproved PVR. TmLRP had the best efficacy in improving QoL score. Diode laser vaporization of prostate was superior in improving IPSS and Qmax. Diode laser through vaporization required the shortest time in catheterization, while Nd:YAG was the longest procedure. For the hospitalization time, TUR was the longest and HoLEP was the shortest. TmLRP was related to the lowest postoperative hemoglobin decrease. TmLEP had the least rates of occurrence of hematuria, reoperation and erectile dysfunction. HoLEP was the best choice to reduce the incidence of recatheterization, urinary retention, urinary tract infection, stress urinary incontinence and retrograde ejaculation. The complications such as blood transfusion, urethral stricture, bladder neck contracture were relatively rare in the patients who underwent diode laser vaporization of prostate.

Conclusion:

Compared with other transurethral procedures, thulium, holmium and diode lasers were associated with better efficacy and fewer complications.
A case report of left atrial myxoma-induced acute myocardial infarction and successive stroke
Authors: Wang Qiushuang , Yang Feifei , Zhu Fei , Yao Cunshan
Published: December 2018

Rationale:

Left atrial myxoma is a common primary cardiac tumor, however, due to poor image quality or atypical myxoma images, it is often misdiagnosed by echocardiograph. A case of left atrial myxoma being misdiagnosed as a thrombus, which successively caused acute myocardial infarction (AMI) and stroke, is very rare. Contrast-enhanced echocardiography can play an important role in definitive diagnosis.

Patient concerns:

A 44-year-old woman was diagnosed AMI because of chest pain with no significant stenosis in the coronary arteries. One month later, the patient was suddenly found unconscious, magnetic resonance imaging (MRI) showed acute multiple cerebral infarctions in the left cerebral hemisphere.

Diagnoses:

Left atrial myxoma, acute myocardial infarction, and stroke.

Interventions:

The patient was given a cardiac surgery for tumor resection, the mass was surgically removed and histopathologic findings showed myxoma.

Outcomes:

After several weeks of rehabilitation, the patient was able to resume daily activities without chest discomfort or dyspnea. One year later, echocardiography showed no recurrence of left atrial myxoma. The patient generally was in good condition.

Lessons:

Although myxoma is mostly benign, this patient occurred AMI and stroke because of misdiagnosis. Comprehensive assessments should be performed with multiple imaging methods for cardiac masses. If necessary, contrast-enhanced echocardiography should be used to clarify, so as not to delay the timing of surgery and bring potential risk of death to patients.
Hemolytic jaundice induced by pharmacological dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency
Authors: Wu Shuxie , Wu Gao , Wu Hanbin
Published: December 2018

Rationale:

Hemolysis induced by high dose ascorbic acid (AA) in patients with G6PD deficiency has been reported, but is rare. To our knowledge, this is the first reported case of a male with G6PD deficiency, coexpressed with cholecystolithiasis and cholecystitis, who developed extreme hemolysis and hyperbilirubinemia after receiving pharmacological doses ascorbic acid infusion.

Patient concerns:

A 27-year-old man history with glucose-6-phosphate dehydrogenase deficiency was admitted to our hospital because of cholecystolithiasis and cholecystitis. He appeared with scleral jaundice and very deep colored urine after receiving pharmacological doses ascorbic acid infusion.

Diagnoses:

Clinical findings when combined with his medical history and various laboratory results confirmed the diagnosis as hemolysis and hyperbilirubinemia induced by ascorbic acid.

Interventions:

The patient was treated with steroids, hepatoprotective drugs, and folic acid in addition avoidance of agents with known hemolysis risk (such as vitamin C).

Outcomes:

As a result, the patient's symptoms from hemolytic jaundice improved, hemoglobin remained stable, and the patient was discharged 11 days later.

Lessons:

Clinicians should bear in mind the possibility that vitamin C exposure may result in hemolysis in patients with G6PD deficiency, especially in those with known severe disease.
Tea consumption is associated with decreased risk of oral cancer
Authors: Zhou Hao , Wu Weiwei , Wang Fengqin , Qi Huizhong , Cheng Zhigang
Published: December 2018

The associations of tea consumption with risk of oral cancer remain not clear. The present meta-analysis aims to clarify the real relationship between tea intake and the risk of oral cancer and quantifies the potential dose-response relationship between them.

A Web search was performed within Pubmed, Embase, and Web of Science databases to identify potential studies that evaluated the relationship between tea consumption and the risk of oral cancer on Mar 21th, 2018 without language restriction. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and combined to evaluate the strength of associations. Dose-response analysis was performed to quantitate the relationship between tea intake and risk of oral cancer.

Total 14 articles were included in the final analysis. The pooled OR for evaluating the risk of oral cancer and tea intake was 0.700 (95% CI = 0.609–0.805, P <.001). The linearity model of dose-response analysis indicated that with increased 1 cup daily, the risk of oral cancer decreased by 6.2% degree (OR = 0.938, 95% CI = 0.922–0.955, P <.001). Subgroup analysis indicated an inverse association between tea intake and the risk of oral cancer except subgroup analysis of black tea and American people.

These results suggest tea intake provides protection against oral cancer carcinogenesis. Additionally, more large-scale pooling and high-quality studies are necessary for detecting the precise relationship between tea intake and oral cancer risk in the future.
Primary iliopsoas abscess combined with rapid development of septic shock
Authors: Deng Yingying , Zhang Yanlong , Song Lianxin , Zhang Xuebin , Shen Zheyuan , Li Zhengqiang , Zhang Lichuang , Peng Aqin
Published: December 2018

Rationale:

Primary iliopsoas abscess (IPA), an uncommon clinical entity, often has no specific clinical features, and advanced imaging techniques are often required for diagnosis.

Patient Concerns:

We successfully treated 3 patients with primary IPA complicated by rapid development of septic shock within 2 months.

Diagnosis:

All patients were in shock at the time of admission and were diagnosed with primary IPA by history, clinical examination and imaging findings.

Interventions:

All patients were treated by surgical drainage and sensitive antibiotics based on culture results.

Outcomes:

The patients eventually recovered and were discharged within 2 months.

Lessons:

An IPA may not be diagnosed in a timely manner because it has no specific symptoms or signs. Therefore, special attention must be given to patients with sudden onset of abdominal pain, hip pain, or high fever without an obvious cause, a primary IPA should be highly suspected in such patients.
An unusual case of intraosseous mucoepidermoid carcinoma of the mandible
Authors: Li Xiang , Wang Feng , Wang Yufan , Sun Shuai , Yang Hongyu
Published: December 2018

Rationale:

Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy. Ectopic MEC can occur in any part of the body, however, only 2% to 4% of MEC could be detected in the jaw, which is named intraosseous mucoepidermoid carcinoma (IMC). IMC is usually a low-grade carcinoma. Uni- or multilocular radiographic lesions should be differential diagnosed with ameloblastoma, odontogenic cysts, and glandular odontogenic cyst (GOC). Radical surgery may prefer for a favorable prognosis. Whereas IMC can recur long after the operation, a long-term follow-up system should be implemented. Owing to its rarity and controversial issues, we report a case report and review the literature to discuss its clinical features, treatments, radiological, and histological characteristics.

Patient concerns:

The patient presented with a 2-month history of mild pain in the lower left posterior jaw without history of surgery or trauma to the mandible.

Diagnoses:

Routine postoperative pathology showed that the mass was consistent with a mandibular mucoepidermoid carcinoma.

Intervention:

Radical surgery and digital mandibular reconstruction were performed.

Outcome:

Postoperative imaging showed that the height of the mandible and the symmetry of the mandible were satisfactory. The patient was also satisfied with her appearance. Follow-up has been established.

Lessons:

Effective surgical treatment allows patients to have a favorable prognosis. A long-term follow-up system should be practiced, because local recurrences and regional metastasis could happen even after decades.
The changes and prognostic value of liver function in young adults with severe burn
Authors: Gong Yan , Long Xianming , Xu Hua , Yang Xinjing , Guo Qiang
Published: December 2018

To analyze the changes in liver functions and the relationship between alterations in liver function and mortality risk in young adults with third-degree burn wounds on over 90% of the total body surface area (TBSA).

A total of 23 fatally burned factory workers in an inflammable dust explosion and fire were enrolled from 2 intensive care units. Clinical data, particularly the laboratory tests for liver function, were retrospectively analyzed and compared between the survivor and non-survivor groups.

Compared to survivors, non-survivors had significantly higher total bilirubin (TBIL), glutamate-pyruvate transaminase (GPT), glutamic-oxaloacetic transaminase, alkaline phosphatase, prothrombin time, and activated partial thromboplastin time (APTT) at the terminal point of this study (P <.05). In addition, the peak values of TBIL, GPT, and longer APTT were higher in non-survivors than in survivors during hospital course, and the peak values of TBIL was one of major prognostic factors for mortality risk. Furthermore, at the first 2 weeks, the cumulative survival rates were significantly lower in patients with liver dysfunction than those without liver dysfunction (P <.01).

Our findings show that the great changes in liver function occurred in first 2 weeks after severe burns. Liver dysfunction may have an effect on clinical outcomes of post-burn. Measures to protect liver function and prevent from deterioration could be beneficial in improvement survival rate, especially during the first 2 weeks.
Delayed recovery of pediatric sudden sensorineural hearing loss treated with acupuncture
Authors: Kim Min Hee , Kim Bong Hyun , Kang Minseo , Choi Inhwa
Published: December 2018

Rationale:

The rate of spontaneous recovery of sudden sensorineural hearing loss (SSNHL) has been reported to be as high as 32% to 65%. Although the majority of spontaneous recoveries occur within 2 weeks, treatment of refractory SSNHL failing conventional therapy is difficult. In particular, it is more difficult to treat children—who have a worse prognosis than adults—with SSNHL refractory to conventional therapy. No studies reported delayed recovery of pediatric SSNHL later than 3 months after onset, or delayed recovery treated with acupuncture.

Patient concerns:

A 15-year-old girl experienced hearing loss after acquiring a cold.

Diagnosis:

She did not undergo audiometry and only took medicine for a common cold after diagnosis by an internal medicine doctor. Ninety-three days after onset, she visited an otorhinolaryngology clinic and was diagnosed with SSNHL. Seven rounds of intratympanic steroid (ITS) treatment were performed 93 to 135 days after onset; audiogram at 149 days did not demonstrate improvement.

Interventions:

Two-hundred sixty-six days after onset, she visited to TKM hospital and was admitted for 21 days and received outpatient treatment for 1 month after discharge. She was treated acupuncture, transcutaneous electrical nerve stimulation, and moxibustion.

Outcomes:

She experienced improvement in experienced improvement in pure tone average, speech recognition threshold, and word recognition scores after acupuncture treatment. Delayed ITS treatment at 93 to 135 days after onset did not improve the patient's hearing loss. However, slight recovery was achieved at the conclusion of treatment. Lessons: Acupuncture may be a therapeutic option for individuals who do not experience improvement after the use of steroids or miss early treatment.
Giant sacrococcygeal chordoma
Authors: Xu Qiang , Gu Houyun , Liu Xuqiang , Liu Hucheng , Zhou Yibiao , Chen Guiping , Dai Min , Zhang Bin
Published: December 2018

Rationale:

Chordoma is a relatively rare tumor that accounts for 1% to 4% of all malignant bone tumors, with an annual incidence of <0.1 per 100,000 people. Although chordoma is aligned with the axis of the spine and most commonly develops in the sacrum, to the best of our knowledge, giant sacrococcygeal chordoma is extremely rare.

Patient concerns:

A 61-year-old Chinese man presented with a massive dorsal sacral mass. The patient's primary complaint was that, during the last two months, the mass had been increasing in size and his right lower extremity was uncomfortable while he was sitting, although the discomfort was relieved when he was standing.

Diagnoses:

Based on the imaging findings, we suspected that the sacrococcygeal mass was a chordoma, and a postoperative pathological examination confirmed the diagnosis of a sacral chordoma.

Intervention:

The patient underwent extensive open surgery to achieve complete resection of the sacrococcygeal mass. An occlusion balloon catheter was used in the abdominal aorta to minimize intraoperative bleeding and maintain a clear surgical field.

Outcomes:

The patient was discharged without complications at 27 days after surgery. The 3-month follow-up revealed that the patient had recovered well, the discomfort in his right lower extremity while standing had completely resolved and that there was no evidence of recurrence.

Lessons:

The development of chordoma is not associated with clear symptoms, although early diagnosis and treatment are needed to prevent invasion of the nearby tissues and organs. Therefore, we believe that surgical treatment of sacral chordoma is effective, although care must be taken to completely remove all residual tumor tissue and reduce the risk of recurrence. Besides, This report adds to our limited understanding of the rare giant sacrococcygeal chordoma.
Case report of a novel PCDH19 frameshift mutation in a girl with epilepsy and mental retardation limited to females
Authors: Zhang Xinying , Chen Na , Ma Aihua , Wang Xueyu , Sun Wenxiu , Gao Yuxing
Published: December 2018

Rationale:

Epilepsy with mental retardation limited to females (EFMR) is a rare type of X-linked epilepsy disorder, affecting heterozygous females disproportionately. The pathogenesis of EFMR has been identified as mutations in the protocadherin 19 (PCDH19) gene. To data, more than 60 different mutations in PCDH19 have been identified. Most of them are located at exon 1, but we describe a novel deletion mutation c.2468delT at exon 3 of PCDH19.

Patient concerns:

The patient was an 11-year-old girl with onset of seizures at the age of 18 months and followed by progressive intellectual disability (ID) later.

Diagnosis:

The girl was diagnosed as EFMR when a novel deletion mutation c.2468delT at exon 3 of PCDH19 was found. The deletion mutation c.2468delT was predicted to have caused a frameshift mutation of amino acid at position 823 (p.L823fs). There was no family history of seizures or ID. Her father was asymptomatic, but the mutation screening shows that he had a hemizygous mutation c.2468delT at the same site of PCDH19. The secondary structure of PCDH19 (wide type) showed that the sequences undergoing frameshift mutations were located in the cytoplasm and contain 9 phosphorylation sites. The p.L823fs mutation caused a totally different amino sequence after position of 823, thereby resulting in the disappearance of phosphorylation sites. The frameshift mutation of amino acid at position 823 might affect its binding capability with GABAA receptor and results in migration and morphological maturation of hippocampal neurons.

Interventions:

The patient has received antiepileptic treatments, including sodium valproate, carbamazepine, levetiracetam, topiramate and clonazepam et al.

Outcomes:

The antiepileptic treatment effects were limited.

Lessons:

This case report describes a novel PCDH19 gene mutation (c.2468delT) at exon 3 in a girl suffering from EFMR. The deletion mutation was predicted to cause a frameshift mutation-p.L823fs, which is highly conserved across different species.
The clinical effects of probiotics for inflammatory bowel disease
Authors: Jia Kai , Tong Xin , Wang Rong , Song Xin
Published: December 2018

Background:

As the exact pathogenesis of inflammatory bowel disease (IBD) is not known, there is increasing evidence of clinical trials and animal models that indicate the beneficial effects of probiotics.

Methods:

Multiple databases were adopted to search for the relevant studies involving the comparison between probiotics and control groups. Review Manager 5.0 was used to assess the efficacy among included articles. Risk of bias for the articles included was also conducted.

Results:

Finally, 10 studies eventually met the inclusion criteria and 1049 patients were included. The meta-analyses showed that no significant differences of remission, relapse, and complication rate between Escherichia coli Nissle 1917 and mesalazine groups (RR = 0.94, 95%CI [0.86, 1.03], P = .21; RR = 1.04, 95%CI [0.82, 1.31], P = .77; RR = 1.12, 95%CI [0.86, 1.47], P = .39, respectively). Despite the fact that no significant differences of remission, relapse, and complication rate were observed in overall meta-analysis results between probiotics and placebo group, the subgroup analyses suggested that VSL#3 presented a higher remission rate and lower relapse rate (RR = 1.67, 95%CI [1.06, 2.63], P = .03; RR = 0.29, 95%CI [0.10, 0.83], P = .02, respectively).

Conclusion:

Some types of probiotics, such as E coli Nissle 1917 and VSL#3, could be used as alternative therapy for patients with IBD.
Evaluation of the effectiveness and safety of a daily dose of 5 mg of tadalafil, over an 8-week period, for improving quality of life among Korean men with andropause symptoms, including erectile dysfunction
Authors: Lee Joong Gyo , Kim Byung Duk , Han Chang Hee , Lee Kang Kon , Yum Keun Sang
Published: December 2018

Background:

The primary aim of this study was to evaluate the effects of a once-a-day 5 mg dose of tadalafil, prescribed for 8 weeks, on the quality of life (QoL) of South Korean men with andropause symptoms, including erectile dysfunction (ED), using a single group, open-labeled, before-and-after preliminary trial. The secondary objective was to evaluate the effectiveness and safety of tadalafil for ED.

Methods:

Forty South Korean men (>35 years of age) with andropause symptoms including ED were enrolled into our trial. Andropause syndrome was defined using the androgen deficiency in aging males (ADAM) questionnaire and other screening tests, including testosterone levels. The following outcome measures were obtained at baseline and at 4 and 8 weeks of tadalafil treatment: physical examination, adverse effects, Short Form 12 Health Survey (SF-12) score, International Index of Erectile Function (IIEF-5) score, bioelectrical impedance analysis (BIA), and free radical testing.

Results:

Treatment increased the SF-12 Mental component score, used as a proxy measure of quality of life, from baseline to at 4 and 8 weeks (P < .05). In addition, the mean IIEF-5 score, which assesses sexual function, increased from baseline at 4 and 8 weeks (P < .05), with this increase being significant at both time points. No adverse effects were noted.

Conclusion:

Tadalafil (5 mg dose, once daily) is a safe and effective treatment to improve ED, and overall QoL, among Korean men with andropause symptoms, including ED.
Reverse turnover pedicled latissimus dorsi muscle flap for lower back reconstruction
Authors: Kang Soo Hwan , Kim Yoo Chang , Sur Yoo Joon
Published: December 2018

Rationale:

Large soft tissue defects on the lower back represent a treatment challenge. Among a variety of reconstructive procedures, the latissimus dorsi (LD) muscle or musculocutaneous flap is one of most frequently used pedicled flaps. However, the pedicled LD flap carries a bulky pivot point and a short arc of rotation. If a pedicled LD muscle flap is transferred using a reverse turnover pattern, theses drawbacks can be avoided.

Patient concerns:

The first patient was a 56-year-old man with hepatocellular carcinoma and multiple bone metastases involving D11-L4 vertebral bodies. A chronic ulcer was developed on his lower back area after palliative radiation therapy for bone metastases. The second patient was a 41-year-old man with a soft tissue mass on his lower back, which was diagnosed as dermatofibrosarcoma protuberans via previous incisional biopsy. A large soft tissue defect was developed on his lower back as a result of a wide resection.

Diagnosis:

Both patients were referred to our department for the treatment of a large soft tissue defect on lower back.

Interventions:

They underwent the reverse turnover pedicled LD muscle flap and split-thickness skin graft.

Outcomes:

At postoperative 6-month follow-up, both patients remained free of wound problem.

Lessons:

The reverse turnover pedicled LD muscle flap is quite straightforward. Even if a soft tissue defect in the lower back is large or complicated by infection or radiation therapy, perfusion of LD by posterior intercostal arteries is likely to be preserved. We recommend the reverse turnover pedicled LD muscle flap as an effective alternative for reconstruction of soft tissue defects involving the lower back.
Disease-specific Hospitalizations Among 5-Year Survivors of Hepatoblastoma: A Nordic Population-based Cohort Study
Authors: Bonnesen Trine G. , Asdahl Peter H. , de Fine Licht Sofie , Gudmundsdottir Thorgerdur , Holmqvist Anna S. , Madanat-Harjuoja Laura-Maria , Tryggvadottir Laufey , Winther Jeanette F. , Hasle and Henrik
Published: December 2018

Introduction:

The long-term risk of somatic disease in hepatoblastoma survivors has not been thoroughly evaluated in previous studies. In this population-based study of 86 five-year HB survivors, we used inpatient registers to evaluate the risk for a range of somatic diseases.

Methods:

In total, 86 five-year survivors of hepatoblastoma were identified in the Nordic cancer registries from 1964 to 2008 and 152,231 population comparisons were selected. Study subjects were followed in national hospital registries for somatic disease classified into 12 main diagnostic groups. Standardized hospitalization rate ratios (RRs) and absolute excess risks were calculated.

Results:

After a median follow-up of 11 years, 35 of the 86 five-year hepatoblastoma survivors had been hospitalized with a total of 69 hospitalizations, resulting in an RR of 2.7 (95% confidence interval [CI], 2.2-3.5) and an overall absolute excess risk of 4.2 per 100 person-years. Highest risk was seen for benign neoplasms (RR=16) with 6 hospitalizations for benign neoplasms in the colon and one in rectum.

Conclusions:

The pattern of hospitalizations found in this first comprehensive follow-up of hepatoblastoma survivors seems reassuring. Less than 50% of the 5-year survivors had been hospitalized and often for diseases that were not severe or life-threatening.
Clinicopathologic and Molecular Features of Metastatic Follicular Thyroid Carcinoma in Patients Presenting With a Thyroid Nodule Versus a Distant Metastasis
Authors: Cracolici Vincent , Kadri Sabah , Ritterhouse Lauren L. , Segal Jeremy P. , Wanjari Pankhuri , Cipriani Nicole A.
Published: December 2018

Metastatic follicular thyroid carcinoma (FTC) is rare. The aim of this study was to determine the clinical, histologic, and molecular differences between patients with metastatic FTC who present with distant metastatic (DM) disease versus those who present with a primary thyroid nodule (PT). Clinical and pathologic information was extracted from the medical record and surgical pathology report. When available, slides were reviewed. Molecular testing was performed on available primary and/or metastatic lesions. Thirty-six patients with metastatic FTC were identified: 15 DM and 21 PT. DM patients were significantly older than those with PT (P=0.0001). In DM patients, bone was the most common site of initial metastasis (P=0.03), compared with lung in PT patients (P=0.03). Unique to primary carcinomas in DM patients was extensive intratumoral fibrosis (50%), occasionally reaching such a degree as to obscure histologic features of malignancy (2 cases). Oncocytic features were more common in those who presented with PT (P=0.03). Pathogenic mutations were identified in 85% of cases, most commonly in RAS (55%) and TERT promoter (45%); of these, combined RAS and TERT was present in 30%. Pathogenic PTEN, NF1, RET, and BRCA2 mutations were also identified. The prevalence and type of pathogenic mutations did not differ between DM and PT patients. The acquisition of a pathogenic mutation in the metastatic focus that was not present in the primary carcinoma was rare (1 case). In summary, FTC presenting with DM compared with PT was more likely to be present in an older age group, to metastasize to bone, and to demonstrate extensive fibrosis possibly representing histologic regression.
Effective Connectivity in Subjects With Mild Cognitive Impairment as Assessed Using Functional Near-Infrared Spectroscopy
Authors: Bu Lingguo , Huo Congcong , Qin Yuexia , Xu Gongcheng , Wang Yonghui , Li Zengyong
Published: December 2018

Objective

This study aimed to reveal the physiological mechanism in subjects with mild cognitive impairment based on effective connectivity method.

Methods

Effective connectivity was assessed by dynamic Bayesian inference of the oxygenated hemoglobin concentration signals measured through functional near-infrared spectroscopy. The oxygenated hemoglobin concentration signals were recorded from the left prefrontal cortex, right prefrontal cortex, left motor cortex, right motor cortex, left occipital lobe, and right occipital lobe of 26 subjects with mild cognitive impairment (mild cognitive impairment group) and 28 healthy elderly subjects (control group) at resting state.

Results

The coupling strength of right prefrontal cortex to left prefrontal cortex (F = 7.964, P = 0.007) and left prefrontal cortex to right occipital lobe (F = 4.278, P = 0.044) in interval III as well as left prefrontal cortex to left occipital lobe (F = 5.637, P = 0.021), right occipital lobe to left prefrontal cortex (F = 4.762, P = 0.034), and right prefrontal cortex to left occipital lobe (F = 4.06, P = 0.049) in interval IV in the mild cognitive impairment group were significantly lower than those in the control group.

Conclusions

The decreased effective connectivity levels among brain regions may be a marker of impaired cognitive function in the mild cognitive impairment group. The constructed effective connectivity network based on functional near-infrared spectroscopy provide a noninvasive method to assess mild cognitive impairment.
Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5
Authors: Johnston Keira J.A. , Adams Mark J. , Nicholl Barbara I. , Ward Joey , Strawbridge Rona J , McIntosh Andrew , Smith Daniel J. , Bailey Mark E.S.
Published: December 2018

Chronic pain is highly prevalent worldwide, with a significant socioeconomic burden, and also contributes to excess mortality. Chronic pain is a complex trait that is moderately heritable and genetically, as well as phenotypically, correlated with major depressive disorder (MDD). Use of the Conditional False Discovery Rate (cFDR) approach, which leverages pleiotropy identified from existing GWAS outputs, has been successful in discovering novel associated variants in related phenotypes. Here, genome-wide association study outputs for both von Korff chronic pain grade as a quasi-quantitative trait and for MDD were used to identify variants meeting a cFDR threshold for each outcome phenotype separately, as well as a conjunctional cFDR (ccFDR) threshold for both phenotypes together. Using a moderately conservative threshold, we identified a total of 11 novel single nucleotide polymorphisms (SNPs), six of which were associated with chronic pain grade and nine of which were associated with MDD. Four SNPs on chromosome 14 were associated with both chronic pain grade and MDD. SNPs associated only with chronic pain grade were located within SLC16A7 on chromosome 12. SNPs associated only with MDD were located either in a gene-dense region on chromosome 1 harbouring LINC01360, LRRIQ3, FPGT and FPGT-TNNI3K, or within/close to LRFN5 on chromosome 14. The SNPs associated with both outcomes were also located within LRFN5. Several of the SNPs on chromosomes 1 and 14 were identified as being associated with expression levels of nearby genes in the brain and central nervous system. Overall, using the cFDR approach, we identified several novel genetic loci associated with chronic pain and we describe likely pleiotropic effects of a recently identified MDD locus on chronic pain.

Author Summary

Genetic variants explaining variation in complex traits can often be associated with more than one trait at once (‘pleiotropy’). Taking account of this pleiotropy in genetic studies can increase power to find sites in the genome harbouring trait-associated variants. In this study we used the suspected underlying pleiotropy between chronic pain and major depressive disorder to discover novel variants associated with chronic pain, and to investigate genetic variation that may be shared between the two disorders.
Performance - Based Clustering Enables the Study of Physiological Features Supporting Sustained Attention Capacities
Authors: Marques-Carneiro José Eduardo , Staub Bérengère , Bonnefond Anne
Published: December 2018

In the present study, we investigated different sustained attention performance profiles in the general adult population and if age is a determinant factor among these profiles. We also reported some specificities in terms of brain oscillations. The sustained attention to response task was applied combined with electrophysiological recordings in 59 adults, aged from 19 to 86 years. We used a hierarchical cluster analysis to group individuals based on similarity of levels and patterns of performance across variables of interest. We focused on the most common attentional–related variables, which allowed us to identify four distinct clusters showing specific sustained attention profiles. Furthermore, our analysis clearly revealed that age was not the determinant factor of these profiles. Finally, we highlighted specificities in terms of brain oscillations. Subjects from cluster 1– the “high-performers” – demonstrated a globally increased theta-gamma coupling maintained over time and an increase of theta activity at the FC6 and F8 electrodes. Subjects from cluster 2, who adopted a more cautious response strategy, presented a higher level of modulation exerted by the electrode FT7 over Oz and a higher theta-gamma coupling at the Oz. This result suggests that cluster-based method to useful in understanding specific mechanisms underlying sustained attention features.
Parallel genomic evolution of parasite tolerance in wild honey bee populations
Authors: Bozek Katarzyna , Rangel Juliana , Arora Jatin , Tin Mandy , Crotteau Emily , Loper Gerald , Fewell Jennifer , Mikheyev Alexander
Published: December 2018

Sudden biotic pressures, such as those from novel diseases and pathogens, require populations to respond rapidly or face potential extinction. How this response process takes place remains poorly understood, particularly in natural environments. In this study we take advantage of unique decade-long data sets of two wild honey bee (Apis mellifera) populations in the United States to reconstruct the evolution of tolerance to a novel parasite, the ectoparasitic mite Varroa destructor. Upon the arrival of Varroa, the two geographically isolated populations simultaneously suffered massive Varroa-induced mortality, but stabilized within two years. Here we sequenced and phased genomes of 465 bees sampled from both populations annually over the decade that spanned Varroa's arrival. Remarkably, we found that genetic changes were strongly correlated between the populations, suggesting parallel selective responses to Varroa parasitization. The arrival of Varroa was also correlated with an influx of genes of African origin into both populations, though surprisingly it did not substantially contribute to the overall similarity of the evolutionary response between them. Genes involved in metabolic, protein processing and developmental pathways were under particularly strong selection. It is possible that interactions among highly connected gene groups in these pathways may help channelize selective responses to novel parasites, causing completely unrelated populations to exhibit parallel evolutionary trajectories when faced with the same biotic pressure. Our analyses illustrate that ecologically relevant traits emerge from highly polygenic selection involving thousands of genes contributing to complex patterns of evolutionary change.
A Benchmark of Computational CRISPR-Cas9 Guide Design Methods
Authors: Bradford Jacob , Perrin Dimitri
Published: December 2018

The popularity of CRISPR-based gene editing has resulted in an abundance of tools to design CRISPR-Cas9 guides. This is also driven by the fact that designing highly specific and efficient guides is a crucial, but not trivial, task in using CRISPR for gene editing. Here, we thoroughly analyse the performance of 17 design tools. They are evaluated based on runtime performance, compute requirements, and guides generated. To achieve this, we implemented a method for auditing system resources while a given tool executes, and tested each tool on datasets of increasing size, derived from the mouse genome. We found that only five tools had a computational performance that would allow them to analyse an entire genome in a reasonable time, and without exhausting computing resources. There was wide variation in the guides identified, with some tools reporting every possible guide while others filtered for predicted efficiency. Some tools also failed to exclude guides that would target multiple positions in the genome. We also considered a collection of over a thousand guides for which experimental data is available. For the tools that attempt to filter based on efficiency, 65% to 85% of the guides they reported were experimentally found to be efficient, but with limited overlap in the sets produced by different tools. Our results show that CRISPR-Cas9 guide design tools need further work in order to achieve rapid whole-genome analysis and that improvements in guide design will likely require combining multiple approaches.