bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic effect of minimally invasive catheter drainage and local chemotherapy for the lumbosacral tuberculosis without neural symptoms
Authors: Li Tian-qing , Ma Zhen-sheng , Zhang Yang , Xu Hui-fa , Lei Wei
Published: June 2019

Increasing number of studies have shown growing incidence of lumbosacral tuberculosis and its complications. However, the treatment options for this disorder are still limited.

To evaluate the long-term therapeutic effect and prognosis of minimally invasive puncture catheter drainage and Isoniazid local chemotherapy for the treatment of lumbosacral tuberculosis without neural symptoms under the guidance of computed tomography (CT).

A total of 45 patients with asymptomatic lumbosacral tuberculosis were treated by minimally invasive catheter drainage under CT guidance. Forty-two cases had been followed up, which included 22 women and 20 men with an average age of 36.45 years old. Isoniazid was injected locally and antituberculotic drugs were administered for postoperative treatment. Oswestry Disability Index (ODI), visual analogue scale (VAS) evaluation and Cobb angle were recorded before and after operation.

Forty-two patients had been followed up and the follow-up term was from 1.2 to 8.5 years (average 60 months). All patients were healed without recurrent cases. The ODI were improved from 14.86 ± 2.02 before operation to 1.48 ± 1.55 after operation. The post-operative (4.19 ± 1.17) VAS score was improved compared to the pre-operative VAS score (0.55 ± 0.55). The post-operative Cobb angle (6.19° ± 3.85°) was also improved relatively to the preoperative Cobb angle (5.90° ± 3.71°).

Minimally invasive puncture catheter drainage combined with Isoniazid local chemotherapy is an effective method for lumbosacral tuberculosis without neural symptom. Meanwhile, it can be applied for the treatment of spinal tuberculosis before open surgery.
Epidemiologic characteristics and risk factors in patients with ketamine-associated lower urinary tract symptoms accompanied by urinary tract infection
Authors: Liu Weihua , Wu Weiwei , Wei Yongbao , Wu Jinfeng , Li Tao , Zhu Qingguo , Ye Liefu , Hong Fuyuan , Gao Yunliang , Yang Jinrui
Published: June 2019

Young adults with longstanding ketamine abuse present with lower urinary tract symptoms (LUTSs), which may be accompanied by urinary tract infection (UTI). However, the morbidity and risk factors for ketamine-associated LUTS accompanied by UTI (KALAUTI) are still unknown. To ascertain these, we surveyed patients with a history of ketamine abuse and LUTS at the time of their initial presentation.

One hundred untreated patients with ketamine-associated LUTS were initially surveyed at 3 medical institutions. The patients’ basic demographic and clinical information, KALAUTI status, and possible risk factors were obtained via a questionnaire and analyzed.

Eighty-one patients were finally enrolled. Eight patients (9.88%) had a definitive diagnosis of KALAUTI and 16 (19.75%) had suspected KALAUTI. The diagnosis of KALAUTI was ruled out in the remaining 57 patients (70.37%). Patients with upper urinary tract involvement, longer duration of drug use, or more severe LUTS (P < .05), were more prone to KALAUTI. Frequent urine culture and a higher voiding symptom score (VSS) were risk factors for KALAUTI (P < .05), increasing the risk of KALAUTI by 44.241- and 1.923-fold, respectively.

The study indicates that frequent urine culture and severe VSS are risk factors for KALAUTI. The possibility of UTI should be considered in ketamine abusers with LUTS in the clinical setting.
Perceived stress and psychological distress among chinese physicians
Authors: Wang Yan , Wang Ping
Published: June 2019

Although the association between perceived stress and psychological distress has been demonstrated, the mechanism behind the association is not well understood in physicians. The purpose of this study was to examine how coping styles (positive and negative) mediated the association between perceived stress and psychological distress among Chinese physicians.

A cross-sectional survey was conducted in Liaoning Province, China, between October and December 2017. Self-administered questionnaires, including the General Health Questionnaire to assess psychological distress, the Stress Reaction Questionnaire to assess perceived stress, and the Trait Coping Style Questionnaire to assess coping style, as well as surveys of demographic and occupational characteristics, were distributed to 1120 physicians employed in large general hospitals. The final sample consisted of 1051 participants. Asymptotic and resampling strategies were used to examine how coping style mediated the association between perceived stress and psychological distress.

Perceived stress was significantly and positively associated with psychological distress among physicians. Both positive and negative coping significantly mediated the association between perceived stress and psychological distress. For psychological distress and its 3 dimensions (depression, anxiety, and reduced self-affirmation), the proportions of mediating roles of coping styles were 26.1%, 29.9%, 24.8%, and 22.7%, respectively.

Perceived stress had positive effects on psychological distress, and coping style was a mediator in this relationship among Chinese physicians. In addition to reducing stress in clinical practice, appropriate coping styles should be adopted in psychological distress prevention and treatment strategies.
Three-dimensional pseudocontinuous arterial spin labeling and susceptibility-weighted imaging associated with clinical progression in amnestic mild cognitive impairment and Alzheimer's disease
Authors: Huang Qingling , Cao Xuan , Chai Xue , Wang Xiao , Xu Ligang , Xiao Chaoyong
Published: June 2019

Background:

This study aimed to evaluate the value of 3-dimensional pseudocontinuous arterial spin labeling (3D-pcASL) and susceptibility-weighted imaging (SWI) for the early disease-sensitive markers of conversion from amnestic MCI (aMCI) to Alzheimer disease (AD) in this process.

Methods:

Forty patients with aMCI and AD respectively were recruited in the study, and 40 healthy subjects were taken as controls. Data were recorded using 3T MR scanner. We assessed the cerebral blood flow (CBF) in 11 different regions of interest, and counted number of microhemorrhages (MB) in 3 regions of brain lobes, bilateral basal ganglia/thalamus, and brain stem/cerebellum, and then investigated correlations between Montreal Cognitive Assessment (MoCA) scores, CBF, and susceptibility-weighted imaging (SWI) features in these 3 groups.

Results:

The results revealed that for AD patients, the MoCA scores and CBF values in frontal gray matter (FGM), occipital gray matter (OGM), temporal gray matter (TGM), parietal gray matter (PGM), hippocampus, anterior cingulate cortex (ACC), precuneus, posterior cingulate cortex (PCC), precuneus, basal ganglia and thalamus decreased compared with aMCI patients and control group, and significant difference was revealed among the 3 groups. While in cerebellum, statistical significance was only found between AD patients and control group. On SWI, the average numbers of hemorrhage in regions of lobes for AD patients were significantly higher than aMCI patients and control group. The same results occurred in the bilateral basal ganglia/thalamus. We further found the MoCA score was positively correlated with CBF, but negatively correlated with hypointense signal on SWI.

Conclusion:

3D-pCASL and SWI have promising potential to be biomarkers for conversion from aMCI to AD in this process.
Quality of life in patients who undergo conventional or robotic-assisted total laparoscopic hysterectomy
Authors: Rodrigues Rodrigo Corvino , Rodrigues Meline Rossetto Kron , Freitas Noélle de Oliveira , Rudge Marilza Vieira Cunha , Lima Silvana Andréa Molina
Published: June 2019

Background:

Hysterectomy for benign gynecologic diseases, especially dysfunctional uterine bleeding, is one of the most common gynecologic interventions. The uterus can be removed using abdominal, vaginal, laparoscopic, or robotic-assisted laparoscopic hysterectomy. In a robotic-assisted procedure, the surgeon directs the robot while seated at a console in the operating room. This differs from laparoscopic hysterectomy because a “robot” performs the operation, while the surgeon watches a monitor. This systematic review will compare quality of life (QOL) in patients who undergo total robotic-assisted laparoscopic hysterectomy for benign indications and those who undergo conventional laparoscopic surgery.

Methods:

We will perform a systematic review according to the Cochrane Methodology for randomized controlled trials. The review will include studies reporting use of QOL metrics to assess patients who undergo total hysterectomy for benign indications using robotic-assisted technique or conventional laparoscopic surgery. QOL will be the primary outcome and will be measured using validated instruments. An overall search strategy will be developed and adapted for Embase, MEDLINE, LILACS, and CENTRAL databases. Two reviewers will independently select the eligible studies, assess the risk of bias, and extract the data from included studies. Similar outcomes measured in at least 2 trials will be plotted in the meta-analysis using Review Manager 5.3. The quality of evidence will be determined using the GRADE approach.

Results:

This systematic review is designed to provide high quality evidence on QOL in patients undergoing total hysterectomy for benign indications using either robotic-assisted or conventional laparoscopic surgery.

Conclusion:

It is expected that high-quality evidence on QOL can be used to guide decision-making by institutions and clinicians to improve health care; the evidence can also be used in future studies.

PROSPERO registration number:

PROSPERO CRD 42019129913
A retrospective study of patients with systemic lupus erythematosus combined with Pneumocystis jiroveci pneumonia treated with caspofungin and trimethoprim/sulfamethoxazole
Authors: Wang Zhi-Guo , Liu Xue-Ming , Wang Qian , Chen Nan-Fang , Tong Sheng-Quan
Published: June 2019

Systemic lupus erythematosus (SLE) complicated with Pneumocystis jiroveci pneumonia (PCP) is a clinical complex with unsatisfying treatment efficacy and poor prognosis which is difficult to be diagnosed at early stage. The present study aimed to investigate the clinical features of SLE with PCP, recognize the early onset indicating factors, and evaluate the treatment efficacy of combined caspofungin and trimethoprim/sulfamethoxazole (coSMZ).

We reviewed data of 9 patients admitted with SLE-PCP and treated with caspofungin combined with coSMZ at Tangshan Gongren Hospital from January 2013 to December 2017. Patients’ clinical manifestation and laboratory data [leucocyte, lymphocyte, cluster of differentiation 4 (CD4)+T cell, lactate dehydrogenase (LDH), blood gas, etc] were compared before and after treatments. And the early onset factors of SLE-PCP, treatment efficacy of combined caspofungin and CoSMZ were analyzed.

Among these 9 patients, 8 patients suffered renal impairment, and all of them had been taking prednisone in the past 3 months at an average dose of 29.4 ± 13.6 mg/day. In addition, they had taken at least one kind of immunosuppressants. Laboratory data (leucocyte, lymphocyte, CD4+T cell, PaO2, LDH) were remarkably abnormal at hospital admission, but they were improved significantly after 2 weeks of treatment, which is also statistically significant (P < .05), except that leukocyte had no significance change to the value at admission (P = .973). In addition, none of the studied patients died.

The results of the study indicated that long-term use of glucocorticoids and immunosuppressants, low CD4+T cell count, and renal impairment are the early-onset factors for SLE-PCP, caspofungin, when combined with CoSMZ, it could be a promising and effective strategy to treat SLE with PCP.
Efficacy and safety assessment of S-1-based regimens comparing to intravenous fluorouracil-based ones in Asian patients with metastatic colorectal carcinoma
Authors: Chen Jianxin , Wang Junhui
Published: June 2019

Background:

We performed the present systematic review and meta-analysis to evaluate the efficacy and safety for S-1-based regimens comparing to intravenous fluorouracil-based ones in Asian patients with metastatic colorectal carcinoma (mCRC).

Methods:

Eligible prospective and controlled randomized clinical trials (RCT) were included, of which data were extracted by inclusion criteria and exclusion ones. Odds ratio (OR) and Hazard ratio (HR) of outcomes including objective response rate (ORR), disease control rate (DCR), progressive-free survival (PFS), overall survival (OS), and adverse events (AEs) were explored for the final analysis between the 2 groups.

Results:

A total of 23 eligible prospective, controlled RCTs including 2269 patients were enrolled for the pooled analysis. With the meta-analysis of available data, the results of the present research showed that there was no statistical difference on short-term efficacy including ORR (HR = 0.85, 95% CI: 0.71–1.01; P = .07) or DCR (HR = 0.88, 95% CI: 0.69–1.11; P = .27), as well as long-term efficacy including PFS (HR = 1.00, 95% CI: 0.90–1.11; P 
= .98) or OS (HR = 0.95, 95% CI: 0.82–1.10; P 
= .50). In addition, the incidences of AEs including leucopenia, neutropenia, and vomiting were statistically lower in S-1-based regimens comparing to intravenous fluorouracil-based ones, regardless of all grade or high grade (all P <.05). However, there were no significant differences detected among other AEs including anemia, thrombocytopenia, increased alanine aminotransferase concentration, stomatitis, anorexia, diarrhea, hand–foot syndrome (HFS), or sensory neuropathy among the 2 groups (all P >.05).

Conclusions:

The present meta-analysis revealed that S-1-based regimens might be associated with comparable efficacy, as well as lower risk of leucopenia, neutropenia, and vomiting at all/high grade comparing to intravenous fluorouracil-based ones in Asian patients with mCRC.
Implementation of a Weight-Based Protocol for the Management of Steroid-Induced Hyperglycemia
Authors: Myers Alyson K. , Khan Mahmuda , Choi Sebastian , Garnica Patricia , Stoffels Guillaume , Lin Amanda
Published: June 2019

Background:

Hyperglycemia is a recognized complication of supraphysiological steroid dosing. There are no consensus guidelines on optimal treatment of steroid-induced hyperglycemia. We assessed the safety of a weight-based insulin protocol for persons treated with supraphysiological doses of steroids to examine the efficacy of using this protocol in patients with diabetes treated with prednisone or methylprednisolone.

Areas of Uncertainty:

There is uncertainty about the optimal dosing of insulin to manage steroid-induced hyperglycemia; thus, a weight-based protocol was created with the goal of reaching euglycemia faster than current practice in persons with diabetes. Variables such as steroid dosing, baseline glycemic control, and duration of steroid use further complicated the ability to manage these patients.

Innovations:

The interdisciplinary team of diabetes providers and pharmacists worked together to devise a protocol to manage steroid-induced hyperglycemia with the goal of reducing hyperglycemia while avoiding hypoglycemia, as well as to allow for less reliance on endocrine consultation. The protocol used weight, insulin naivety, renal function, blood glucose measurements, and steroid dosing to determine the insulin dose. There was some evidence to suggest the proportion of blood glucose levels more than 200 mg/dL was lower after protocol initiation compared with before protocol initiation (P = 0.053). Several factors decreased the rate of successful outcomes, including minimal primary team participation, accurate completion of calculations based on the protocol, and initiation of the protocol after several days of hyperglycemia.
Updates on antiviral drugs for cytomegalovirus prevention and treatment
Authors: Kotton Camille N.
Published: June 2019

Purpose of review

Cytomegalovirus (CMV) is the most common infection after organ transplant. In addition to causing a viral syndrome and infection, it also increases the risk for complications in the organ transplant, along with higher overall morbidity and mortality. Prevention and ideal treatment of CMV is paramount for optimal outcomes, both for individuals as well as for transplant programs. New guidelines and novel therapies are changing the way we manage disease.

Recent findings

Several new antiviral agents have emerged in recent times, including letermovir, maribavir, and brincidofovir, enhancing our ability to prevent and treat CMV. Recent data on novel agents will be reviewed, with an emphasis on recent guidelines and best practices.

Optimal treatment, influenced by recent advances in the field, including management of resistant virus, results in better outcomes with this significant and virulent virus.
Antimicrobials and Antiepileptics Are the Leading Causes of Idiosyncratic Drug‐induced Liver Injury in American Children
Authors: DiPaola Frank , Molleston Jean P. , Gu Jiezhun , Cirulli Elizabeth T. , Chalasani Naga , Barnhart Huiman , Kleiner David E. , Hoofnagle Jay H. , Fontana Robert J. ,   US Drug Induced Liver Injury Network
Published: June 2019

Objectives:

The aim of this study was to provide an overview of the presenting features, etiologies, and outcomes of children enrolled in the Drug‐induced Liver Injury Network (DILIN) prospective and retrospective studies.

Methods:

Consecutive definite, highly likely, or probable cases in children enrolled into the ongoing DILIN prospective and retrospective studies between September 2004 and February 2017 were reviewed.

Results:

Fifty‐seven cases were adjudicated as definite (14), highly likely (30), or probable (13) DILI. Median age was 14.3 years (1.7–17.9), 67% female, and 82% Caucasian. At DILI onset, 82% had hepatocellular injury with a median alanine aminotransferase of 411 U/L (33–4185), alkaline phosphatase 203 U/L (62–1177), and total bilirubin 3.3 mg/dL (0.2–33.9). The median duration of suspect medication use was 55 days (1–2789) and the most frequently implicated individual agents were minocycline (n = 11) and valproate (n = 6). Sixty‐three percent were hospitalized and 3 (5%) underwent liver transplant within 1 month of DILI onset. Among 46 children followed for at least 6 months, 8 (17%) met criteria for chronic DILI with 6 of them having persistent liver injury at 24 months of follow‐up. A genome‐wide association study in 39 Caucasian children focusing on regions associated with pediatric cholestatic liver disease failed to demonstrate any single nucleotide polymorphism associated with DILI susceptibility or outcome.

Conclusions:

Antimicrobials (51%) and antiepileptic drugs (21%) are the most frequently implicated agents in pediatric DILI patients. Although the majority of cases are self‐limited, there is potential for serious morbidity including acute liver failure, chronic liver injury, and death.
Changes in Anesthetic and Postoperative Sedation–Analgesia Practice Associated With Early Extubation Following Infant Cardiac Surgery: Experience From the Pediatric Heart Network Collaborative Learning Study*
Authors: Amula Venu , Vener David F. , Pribble Charles G. , Riegger Lori , Wilson Elizabeth C. , Shekerdemian Lara S. , Ou Zhining , Presson Angela P. , Witte Madolin K. , Nicolson Susan C.
Published: June 2019

Objectives:

The Pediatric Heart Network sponsored the multicenter Collaborative Learning Study that implemented a clinical practice guideline to facilitate early extubation in infants after repair of isolated coarctation of the aorta and tetralogy of Fallot. We sought to compare the anesthetic practice in the operating room and sedation-analgesia management in the ICU before and after the implementation of the guideline that resulted in early extubation.

Design:

Secondary analysis of data from a multicenter study from January 2013 to April 2015. Predefined variables of anesthetic, sedative, and analgesia exposure were compared before and after guideline implementation. Propensity score weighted logistic regression analysis was used to determine the independent effect of intraoperative dexmedetomidine administration on early extubation.

Setting:

Five children’s hospitals.

Patients:

A total of 240 study subjects who underwent repair of coarctation of the aorta or tetralogy of Fallot (119 preguideline implementation and 121 postguideline implementation).

Interventions:

None.

Measurements and Main Results:

Clinical practice guideline implementation was accompanied by a decrease in the median total intraoperative dose of opioids (49.7 vs 24.0 µg/kg of fentanyl equivalents, p < 0.001) and benzodiazepines (1.0 vs 0.4 mg/kg of midazolam equivalents, p < 0.001), but no change in median volatile anesthetic agent exposure (1.3 vs 1.5 minimum alveolar concentration hr, p = 0.25). Intraoperative dexmedetomidine administration was associated with early extubation (odds ratio 2.5, 95% CI, 1.02–5.99, p = 0.04) when adjusted for other covariates. In the ICU, more patients received dexmedetomidine (43% vs 75%), but concomitant benzodiazepine exposure decreased in both the frequency (66% vs 57%, p < 0.001) and cumulative median dose (0.5 vs 0.3 mg/kg of ME, p = 0.003) postguideline implementation.

Conclusions:

The implementation of an early extubation clinical practice guideline resulted in a reduction in the dose of opioids and benzodiazepines without a change in volatile anesthetic agent used in the operating room. Intraoperative dexmedetomidine administration was independently associated with early extubation. The total benzodiazepine exposure decreased in the early postoperative period.
Detrimental Effects of Psychotropic Medications Differ by Sex in Aging People With HIV
Authors: Mathur Swati , Roberts-Toler Carla , Tassiopoulos Katherine , Goodkin Karl , McLaughlin Milena , Bares Sara , Koletar Susan L. , Erlandson Kristine M. ,   for the ACTG A5322 Study Team
Published: June 2019

Background:

Mental health conditions are common among persons with HIV (PWH). An understanding of factors associated with prescription medication use for these conditions and clinical impact of the prescription medications may improve care of mental health disorders in PWH.

Methods:

Psychotropic medication use was examined among PWH within the AIDS Clinical Trials Group A5322 (HAILO) study. Multivariable logistic models and Cox regression models estimated the association between psychotropic medications (any/none) with baseline and incident slow gait (>1 s/m) and neurocognitive impairment (NCI) for more than 4 years.

Results:

Of 1035 participants, the median age was 51 years.81% were men, 30% black, non-Hispanic, and 20% Hispanic. Psychotropic medication use was similar between men (34%) and women (38%; P = 0.19). PWH using psychotropic medications had greater odds of baseline slow gait {odds ratio 1.61, [95% confidence interval (CI): 1.23 to 2.10]; P < 0.001}. Men but not women using psychotropic medications had an increased risk of developing slow gait [hazard ratio 1.85; (1.29 to 2.65) vs 0.77; (CI: 0.35 to 1.68), P interaction = 0.045]. The sex-specific odds ratios for medication use and NCI were qualitatively but not statistically different [men: 1.79; (1.14–2.80); women: 1.27; (0.56–2.90); P interaction = 0.47]. Psychotropic medication use was associated with an increased risk of incident NCI [hazard ratio 2.18; (95% CI: 1.23 to 3.84), P = 0.007] in both men and women.

Conclusions:

Psychotropic medications are associated with impairment in functional outcomes of aging, with a greater risk of baseline NCI and incident slow gait among men. Further investigation is needed to optimize outcomes in PWH and prescription of psychotropic medications among both men and women.
Is a Postvoid Residual Necessary? A Randomized Trial of Two Postoperative Voiding Protocols
Authors: Willis-Gray Marcella G. , Wu Jennifer M. , Field Christine , Pulliam Samantha , Husk Katherine E. , Brueseke Taylor J. , Geller Elizabeth J. , Connolly AnnaMarie , Dieter Alexis A.
Published: June 2019

Objectives

This study aimed to compare a backfill-assisted voiding trial (VT) with and without a postvoid residual (PVR) after pelvic reconstructive surgery.

Methods

This was a nonblinded randomized controlled trial of women undergoing pelvic organ prolapse and/or stress incontinence surgery. Participants were randomized immediately after surgery to either a PVR VT or a PVR-free VT. Our primary outcome was the rate of VT failure at discharge. Secondary outcomes included days of catheterization, urinary tract infection (UTI), and prolonged voiding dysfunction. With a power of 80% and an α of 0.05, we needed 126 participants to detect a 25% difference in VT failure (60% in PVR VT vs 35% in PVR-free VT).

Results

Participants were enrolled from March 2017 to October 2017. Of the 150 participants, mean age was 59 years, and 33% underwent vaginal hysterectomy, 48% underwent anterior repair, and 75% underwent midurethral sling. Seventy-five (50%) were randomized to PVR VT and 75 (50%) to PVR-free VT, with no differences in baseline demographic or intraoperative characteristics between the 2 groups. Our primary outcome, VT failure, was not significantly different (53% PVR VT vs 53% PVR-free VT, P = 1.0). There were no significant differences in days of postoperative catheterization (1 [0, 4] in PVR VT vs 1 [0, 4] in PVR-free VT, P = 0.90), UTI (20% PVR VT vs 20% PVR-free VT, P = 1.0), or postoperative voiding dysfunction (4% PVR VT vs 5% PVR-free VT, P = 1.0).

Conclusions

When performing a backfill-assisted VT, checking a PVR does not affect VT failure, postoperative duration of catheterization, UTI, or voiding dysfunction.
Gabapentin and Memantine for Treatment of Acquired Pendular Nystagmus: Effects on Visual Outcomes
Authors: Nerrant Elodie , Abouaf Lucie , Pollet-Villard Frédéric , Vie Anne-Laure , Vukusic Sandra , Berthiller Julien , Colombet Bettina , Vighetto Alain , Tilikete Caroline
Published: June 2019

Background:

The most common causes of acquired pendular nystagmus (APN) are multiple sclerosis (MS) and oculopalatal tremor (OPT), both of which result in poor visual quality of life. The objective of our study was to evaluate the effects of memantine and gabapentin treatments on visual function. We also sought to correlate visual outcomes with ocular motor measures and to describe the side effects of our treatments.

Methods:

This study was single-center cross-over trial. A total of 16 patients with chronic pendular nystagmus, 10 with MS and 6 with OPT were enrolled. Visual acuity (in logarithm of the minimum angle of resolution [LogMAR]), oscillopsia amplitude and direction, eye movement recordings, and visual function questionnaires (25-Item National Eye Institute Visual Functioning Questionnaire [NEI-VFQ-25]) were performed before and during the treatments (gabapentin: 300 mg 4 times a day and memantine: 10 mg 4 times a day).

Results:

A total of 29 eyes with nystagmus were evaluated. Median near monocular visual acuity improved in both treatment arms, by 0.18 LogMAR on memantine and 0.12 LogMAR on gabapentin. Distance oscillopsia improved on memantine and on gabapentin. Median near oscillopsia did not significantly change on memantine or gabapentin. Significant improvement in ocular motor parameters was observed on both treatments. Because of side effects, 18.8% of patients discontinued memantine treatment—one of them for a serious adverse event. Only 6.7% of patients discontinued gabapentin. Baseline near oscillopsia was greater among those with higher nystagmus amplitude and velocity.

Conclusions:

This study demonstrated that both memantine and gabapentin reduce APN, improving functional visual outcomes. Gabapentin showed a better tolerability, suggesting that this agent should be used as a first-line agent for APN. Data from our investigation emphasize the importance of visual functional outcome evaluations in clinical trials for APN.
Eumycetoma caused by Cladophialophora bantiana in the United States
Authors: Gniadek Thomas J. , Cappel Mark A. , Wengenack Nancy L. , Libertin Claudia R.
Published: June 2019

A female presented in the sixth decade of life with a history of undifferentiated small cell carcinoma of the right breast in clinical remission, status-post chemotherapy and resection 6 years previously, presented with a chronic anterior knee skin nodule that grew in size over the prior 5–6 weeks. She had no history of opportunistic infections or recent immunosuppression. As it grew, the nodule became tender to touch. Examination revealed a 4–6 mm superficial purple-red nodule. Also, a similar lesion was present on the dorsum of her left foot for the past year, which also recently grew and became tender. The patient did report frequently kneeling on soil when gardening in Florida. She reported no other symptoms. Due to a concern for cutaneous metastasis of the patient’s previously diagnosed small cell carcinoma of the breast, the anterior knee lesion was biopsied. Histology revealed histocyte-rich inflammation with foci of acute inflammation as well as pigmented fungal forms. Subsequent fungal culture of excised tissue grew Cladophialophora bantiana, identified by ribosomal gene DNA sequencing.
Discovering precise temporal patterns in large-scale neural recordings through robust and interpretable time warping
Authors: Williams Alex H. , Poole Ben , Maheswaranathan Niru , Dhawale Ashesh K. , Fisher Tucker , Wilson Christopher D. , Brann David H. , Trautmann Eric , Ryu Stephen , Shusterman Roman , Rinberg Dmitry , Ölveczky Bence P. , Shenoy Krishna V. , Ganguli Surya
Published: June 2019

Though the temporal precision of neural computation has been studied intensively, a data-driven determination of this precision remains a fundamental challenge. Reproducible spike time patterns may be obscured on single trials by uncontrolled temporal variability in behavior and cognition, or may not even be time locked to measurable signatures in either behavior or local field potentials (LFP). To overcome these challenges, we describe a general-purpose time warping framework that reveals precise spike-time patterns in an unsupervised manner, even when spiking is decoupled from behavior or is temporally stretched across single trials. We demonstrate this method across diverse systems: cued reaching in nonhuman primates, motor sequence production in rats, and olfaction in mice. This approach flexibly uncovers diverse dynamical firing patterns, including pulsatile responses to behavioral events, LFP-aligned oscillatory spiking, and even unanticipated patterns, like 7 Hz oscillations in rat motor cortex that are not time-locked to measured behaviors or LFP.
High-yield fabrication of DNA and RNA scaffolds for single molecule force and torque spectroscopy experiments
Authors: Papini Flávia Stal , Seifert Mona , Dulin David
Published: June 2019

Single molecule biophysics experiments have enabled the observation of biomolecules with a great deal of precision in space and time, e.g. nucleic acids mechanical properties and protein-nucleic acids interactions using force and torque spectroscopy techniques. The success of these experiments strongly depends on the capacity of the researcher to design and fabricate complex nucleic acid scaffolds, as the pertinence and the yield of the experiment strongly depend on the high quality and purity of the final scaffold. Though the molecular biology techniques involved are well known, the fabrication of nucleic acids scaffold for single molecule experiments still remains a difficult task. Here, we present new protocols to generate high quality coilable double-stranded DNA and RNA, as well as DNA and RNA hairpins with ~500-1000 bp long stems. Importantly, we present a new approach based on single-stranded DNA’s annealing and show, using magnetic tweezers, that it is more efficient to generate complex nucleic acid scaffolds in larger amount and at higher purity than a standard PCR-digestion-ligation approach. The protocols we describe here enable the design of any sort of complex nucleic acid scaffold for single molecule biophysics experiments and will therefore be extremely valuable to the community.
Improving detection capabilities of a critically endangered freshwater invertebrate with environmental DNA using digital droplet PCR
Authors: Mauvisseau Quentin , Davy-Bowker John , Bulling Mark , Brys Rein , Neyrinck Sabrina , Troth Christopher , Sweet Michael
Published: June 2019

Isogenus nubeculais a critically endangered Plecoptera species. Considered extinct in the UK, the species was recently rediscovered in one location of the river Dee in Wales after 22 years of absence. As many species belonging to the Perlodidae, this species can be a bio-indicator, utilised for assessing water quality and health status of a given freshwater system. However, conventional monitoring of invertebrates via kick-sampling for example, is an invasive and expensive (time consuming). Further, such methods require a high level of taxonomic expertise. Here, we compared the traditional kick-sampling method with the use of eDNA detection using qPCR and ddPCR-analyses. In spring 2018, we sampled eDNA from twelve locations on the river Dee.I. nubeculawas detected using kick-sampling in five of these locations, three locations using both eDNA detection and kick-sampling and one location using eDNA detection alone – resulting in a total of six known and distinct populations of this critically endangered species. Interestingly, despite the eDNA assay being validated in vitro and in silico, and results indicating high sensitivity, qPCR analysis of the eDNA samples proved to be ineffective. In contrast, ddPCR analyses resulted in a clear detection ofI. nubeculaat four locations suggesting that inhibition most likely explains the big discrepancy between the obtained qPCR and ddPCR results. It is therefore important to explore inhibition effects on any new eDNA assay. We also highlight that ddPCR may well be the best option for the detection of aquatic organisms which are either rare or likely to shed low levels of eDNA into their environment.
Using structural analysis in silico to assess the impact of missense variants in MEN1
Authors: Caswell Richard C. , Owens Martina M. , Gunning Adam C. , Ellard Sian , Wright Caroline F.
Published: June 2019

Despite the rapid expansion in recent years of databases reporting either benign or pathogenic genetic variation, the interpretation of novel missense variants can remain challenging, particularly for clinical or genetic testing laboratories where functional analysis is often unfeasible. Previous studies have shown that thermodynamic analysis of protein structure in silico can discriminate between groups of benign and pathogenic missense variants. However, although structures exist for many human disease-associated proteins, such analysis remains largely unexploited in clinical laboratories. Here, we analysed the predicted effect of 338 known missense variants on the structure of Menin, the MEN1 gene product. Results provided strong discrimination between pathogenic and benign variants, with a threshold of >4 kcal/mol for the predicted change in stability providing a strong indicator of pathogenicity. Subsequent analysis of 7 novel missense variants identified during clinical testing of MEN1 patients showed that all 7 were predicted to destabilise Menin by >4 kcal/mol. We conclude that structural analysis provides a useful tool in understanding the impact of missense variants in MEN1, and that integration of proteomic with genomic data could potentially contribute to the classification of novel variants in this disease.
Gq-mediated calcium dynamics and membrane tension modulate neurite plasticity
Authors: Pearce Katherine M. , Bell Miriam , Linthicum Will H. , Wen Qi , Srinivasan Jagan , Rangamani Padmini , Scarlata Suzanne
Published: June 2019

The formation and disruption of synaptic connections during development is a fundamental step in neural circuit formation. Subneuronal structures such as neurites are known to be sensitive to the level of spontaneous neuronal activity but the specifics of how neurotransmitter-induced calcium activity regulates neurite homeostasis are not yet fully understood. In response to stimulation by neurotransmitters such as acetylcholine, calcium responses in cells are mediated the Gαq/phospholipase Cβ (PLCβ)/ phosphatidylinositol 4,5 bisphosphate (PI(4, 5)P2) signaling pathway. Here, we show that prolonged Gαq stimulation results in the retraction of neurites in PC12 cells and rupture of neuronal synapses by modulating membrane tension. To understand the underlying cause, we dissected the behavior of individual components of the Gαq/PLCβ/PI(4, 5)P2pathway during retraction, and correlated these to the retraction of the membrane and cytoskeletal elements impacted by calcium signaling. We developed a mathematical model that combines biochemical signaling with membrane tension and cytoskeletal mechanics, to show how signaling events are coupled to retraction velocity, membrane tension and actin dynamics. The coupling between calcium and neurite retraction is shown to be operative in theC. elegansnervous system. This study uncovers a novel mechanochemical connection between the Gαq/PLCβ/(PI(4, 5)P2pathway that couples calcium responses with neural plasticity.
Agricultural impacts on streams near Nitrate Vulnerable Zones: a case study in the Ebro basin, northern Spain
Authors: Ladrera Rubén , Belmar Oscar , Tomás Rafael , Prat Narcís , Cañedo-Argüelles Miguel
Published: June 2019

Agricultural intensification during the last century has produced river degradation across Europe. From the wide range of pressures derived from agricultural activities that impact rivers, diffuse agricultural pollution has received most of the attention from managers and scientists. The aim of this study was to determine the main pressures exerted by intensive agriculture around Nitrate Vulnerable Zones (NVZs), which are areas of land that drain into waters polluted by nitrates according to the European Nitrate Directive (91/676/EEC). The study area was located in the NW of La Rioja (Northern Spain), which has the highest levels of nitrate concentrations within the Ebro basin. The relationships between forty environmental variables and the taxonomic and functional characteristics of macroinvertebrate assemblages (which are good indicators of water quality) were analyzed in 11 stream reaches differentially affected by upstream agricultural activity. The streams affected by a high percentage of agricultural area had significantly greater nitrate concentrations and distinct macroinvertebrate assemblages dominated by pollution tolerant taxa. Hydromorphological alteration (i.e. channel simplification, riparian forest degradation and sediment inputs), which is closely linked to agricultural practices, was the main factor affecting macroinvertebrate assemblages. Good agricultural practices should be implemented in streams affected by NVZs to reverse stream degradation, in consonance with the European Water Framework Directive (WFD). Management actions in these areas should not focus exclusively on nitrate reduction, but also on restoring riparian and aquatic habitats.
Functional analyses ofSTIM1mutations reveal a common pathomechanism for tubular aggregate myopathy and Stormorken syndrome
Authors: Peche Georges Arielle , Spiegelhalter Coralie , Silva-Rojas Roberto , Laporte Jocelyn , Böhm Johann
Published: June 2019

Tubular aggregate myopathy (TAM) is a progressive disorder essentially involving muscle weakness, cramps, and myalgia. TAM clinically overlaps with Stormorken syndrome (STRMK), associating TAM with miosis, thrombocytopenia, hyposplenism, ichthyosis, short stature, and dyslexia. TAM and Stormorken syndrome arise from gain-of-function mutations inSTIM1orORAI1, both encoding key regulators of Ca2+homeostasis, and mutations in either gene results in excessive Ca2+entry. The pathomechanistic similarities and differences of TAM and Stormorken syndrome are only partially understood. Here we provide functionalin celluloexperiments demonstrating that STIM1 harboring the TAM D84G or the STRMK R304W mutation similarly cluster and exert a dominant effect on the wild-type protein. Both mutants recruit ORAI1 to the clusters, induce major nuclear import of the Ca2+-dependent transcription factor NFAT, and trigger the formation of circular membrane stacks. In conclusion, the analyzed TAM and STRMK mutations have a comparable impact on STIM1 protein function and downstream effects of excessive Ca2+entry, highlighting that TAM and Stormorken syndrome involve a common pathomechanism.
Determinants of stem cell enrichment in healthy tissues and tumors: implications for non-genetic drug resistance
Authors: Weiss Lora D. , van den Driessche P. , Lowengrub John S. , Wodarz Dominik , Komarova Natalia L.
Published: June 2019

Drug resistance is a major challenge for cancer therapy. While resistance mutations are often the focus of investigation, non-genetic resistance mechanisms are also important. One such mechanism is the presence of relatively high fractions of cancer stem cells (CSCs), which have reduced susceptibility to chemotherapy, radiation, and targeted treatments compared to more differentiated cells. The reasons for high CSC fractions (CSC enrichment) are not well understood. Previous experimental and mathematical modeling work identified a particular feedback loop in tumors that can promote CSC enrichment. Here, we use mathematical models of hierarchically structured cell populations to build on this work and to provide a comprehensive analysis of how different feedback regulatory processes that might partially operate in tumors can influence the stem cell fractions during somatic evolution of healthy tissue or during tumor growth. We find that depending on the particular feedback loops that are present, CSC fractions can increase or decrease. We define characteristics of the feedback mechanisms that are required for CSC enrichment to occur, and show how the magnitude of enrichment is determined by parameters. In particular, enrichment requires a reduction in division rates or an increase in death rates with higher population sizes, and the feedback mediators that achieve this can be secreted by either CSCs or by more differentiated cells. The extent of enrichment is determined by the death rate of CSCs, the probability of CSC self-renewal, and by the strength of feedback on cell divisions. Defining these characteristics can guide experimental approaches that aim to screen for and identify feedback mediators that can promote CSC enrichment in specific cancers, which in turn can help understand and overcome the phenomenon of CSC-based therapy resistance.
Room-temperature photo-induced martensitic transformation in a protein crystal. Corrigendum
Authors: Dajnowicz Steven , Langan Patricia S. , Weiss Kevin L. , Ivanov Ilia N. , Kovalevsky Andrey
Published: June 2019

The article by Dajnowicz et al. [IUCrJ (2019). 6, 619–629] is withdrawn.
Synthesis, crystal structure and Hirshfeld surface analysis of 2-chloro-3-[(E)-(2-phenylhydrazinylidene)methyl]quinoline
Authors: Akhramez Soufiane , Hafid Abderrafia , Khouili Mostafa , Saadi Mohamed , El Ammari Lahcen , Ketatni El Mostafa
Published: June 2019

A new quinoline-based hydrazone, C16H12ClN3, was synthesized by a condensation reaction of 2-chloro-3-formylquinoline with phenylhydrazine. The quinoline ring system is essentially planar (r.m.s. deviation = 0.012 Å), and forms a dihedral angle of 8.46 (10)° with the phenyl ring. The molecule adopts anEconfiguration with respect to the central C=N bond. In the crystal, molecules are linked by a C—H...π-phenyl interaction, forming zigzag chains propagating along the [10\overline{3}] direction. The N—H hydrogen atom does not participate in hydrogen bonding but is directed towards the phenyl ring of an adjacent molecule, so linking the chainsviaweak N—H...π interactions to form of a three-dimensional structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H...H (35.5%), C...H/H...C (33.7%), Cl...H/H...Cl (12.3%), N...H/H...N (9.5%) contacts.
A stochastic detailed scheduling model for periodic maintenance of military rotorcraft
Authors: Semaan Nabil M. , Yehia Nabhan
Published: June 2019

Purpose

The purpose of this paper is to develop a stochastic detailed schedule for a preventive/scheduled/periodic maintenance program of a military aircraft, specifically a rotorcraft or helicopter.

Design/methodology/approach

The new model, entitled the military “periodic aviation maintenance stochastic schedule” (PAM-SS), develops a stochastic detailed schedule for a PUMA SA 330SM helicopter for the 50-h periodic inspection, using cyclic operation network (CYCLONE) and Monte Carlo simulation (MCS) techniques. The PAM-SS model identifies the different periodic inspection tasks of the maintenance schedule, allocates the resources required for each task, evaluates a stochastic duration of each inspection task, evaluates the probability of occurrence for each breakdown or repair, develops the CYCLONE model of the stochastic schedule and simulates the model using MCS.

Findings

The 50-h maintenance stochastic duration follows a normal probability distribution and has a mean value of 323 min and a standard deviation of 23.7 min. Also, the stochastic maintenance schedule lies between 299 and 306 min for a 99 per cent confidence level. Furthermore, except the pilot and the electrical team (approximately 90 per cent idle), all other teams are around 40 per cent idle. A sensitivity analysis is also performed and yielded that the PAM-SS model is not sensitive to the number of technicians in each team; however, it is highly sensitive to the probability of occurrence of the breakdowns/repairs.

Practical implications

The PAM-SS model is specifically developed for military rotorcrafts, to manage the different resources involved in the detailed planning and scheduling of the periodic/scheduled maintenance, mainly the 50-h inspection. It evaluates the resources utilization (idleness and queue), the stochastic maintenance duration and identifies backlogs and bottlenecks.

Originality/value

The PAM-SS tackles military aircraft planning and scheduling in a stochastic methodology, considering uncertainties in all inspection task durations and breakdown or repair durations. The PAM-SS, although developed for rotorcrafts can be further developed for any other type of military aircraft or any other scheduled maintenance program interval.