bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Neuromuscular Hip Dysplasia in Children With Cerebral Palsy: Lessons and Challenges
Authors: Davids Jon R.
Published: June 2018

Optimal clinical decision making and surgical management of hip dysplasia in children with cerebral palsy (CP) requires an understanding of the underlying pathophysiology (pathomechanics and pathoanatomy), incidence, and natural history. The incidence of hip dysplasia in children with CP is directly related to the degree of motor impairment. A subluxated or dislocated hip in a child with CP can compromise the quality of life for both the child and their caregivers. The goal of this article is to highlight the events over the last 25 years that have had the greatest impact on the management of hip dysplasia in children with CP. It is my opinion that the 2 most significant advances during this time have been the development of a classification system based upon motor impairment (the Gross Motor Function Classification System), and the development of surveillance programs for hip dysplasia in children with CP. This article will contrast neuromuscular hip dysplasia with developmental dysplasia of the hip. It will be shown how the development and utilization of the Gross Motor Function Classification System has contributed to our understanding of the epidemiology and natural history of hip dysplasia in children with CP, and to the assessment of outcomes following surgical management. The impact of hip surveillance programs on early soft tissue surgeries, skeletal hip reconstructions, and the incidence of hip dislocations and salvage surgeries will be reviewed. Challenges in the implementation of hip surveillance programs in resource poor and decentralized health care delivery systems will be considered, and innovative approaches identified.
Slipped Capital Femoral Epiphysis: The European Perspective
Authors: Wright Jonathan , Ramachandran Manoj
Published: June 2018

Treatment of slipped capital femoral epiphysis remains a contentious and debated issue. The opinion for the correct method of treatment can differ not only between different continents and nations, but also between units and surgeons within individual units. We aim to review the European perspective on the treatment of slipped capital femoral epiphysis and consider the trends for treatment among the European orthopaedic surgical community.
Randomized, Prospective, Open-label Phase III Trial Comparing Mebo Ointment With Biafine Cream for the Management of Acute Dermatitis During Radiotherapy for Breast Cancer
Authors: Geara Fady B. , Eid Toufic , Zouain Nicolas , Thebian Ranim , Andraos Therese , Chehab Chirine , Ramia Paul , Youssef Bassem , Zeidan Youssef H.
Published: June 2018

Purpose:

Acute radiation dermatitis is a common side-effect of radiotherapy in breast cancer and has a profound impact on patients’ quality of life, due to pain and discomfort. The aim of this study is to compare the effect of β-sitosterol (Mebo) ointment to trolamine (Biafine) cream for the prevention and treatment of radiation dermatitis in breast cancer patients receiving adjuvant radiation therapy.

Materials and Methods:

This is a prospective open-label randomized phase III study developed to assess the efficacy of 2 topical agents used for management of acute radiation dermatitis. Female breast cancer patients who needed a course of radiation therapy in our institution were enrolled and randomized into 2 groups 1 with Mebo ointment and 1 with Biafine cream. Both medications were applied twice per day during the whole period of treatment and skin reactions and related symptoms were assessed weekly during the entire course. Grading of skin reactions was done according to the Radiation Therapy Oncology Group grading system.

Results:

Between September 2015 and May 2017, a total of 161 patients were recruited for this trial. Mean age was similar for both groups (50.19±12.57 vs. 51.73±11.23, respectively, P=0.41). All other patients and treatment characteristics were similar in both groups, except for the use of boost (82.7% in the Biafine group vs. 36.7% in Mebo group, P=0.012). Analysis was done for reactions recorded before the beginning of the boost and for the entire course including the boost. Using univariate and multivariate analysis, there was no significant difference in grades 2 and 3 dermatitis between the 2 groups. However, the incidence of severe pruritus and severe local skin pain were both significantly reduced in the Mebo group (14.1% in Biafine vs. 2.9% in Mebo, P=0.016 for pruritus and 11.5% vs. 1.4%, respectively, P=0.02 for severe pain).

Conclusions:

This study showed no difference between Mebo and Biafine in the incidence and severity of breast skin dermatitis during radiation therapy. However, the use of Mebo ointment was associated with decreased severe pruritus and pain which could positively affect patient comfort and quality of life.
Neoadjuvant Chemotherapy Treatment Modifications in Ovarian Carcinoma
Authors: Salman Lina , Ben-Haroush Avi , Raban Oded , Yeoshoua Effi , Sabah Gad , Jakobson-Setton Ariella , Tsoref Daliah , Eitan Ram
Published: June 2018

Objective:

Little is known on the impact of neoadjuvant chemotherapy (NACT) treatment modifications on surgical outcome and progression-free survival (PFS) in patients with ovarian carcinoma. We aimed to report the changes we made during NACT and to evaluate its impact on patient outcome.

Methods:

A retrospective cohort study of all women with advanced stage ovarian carcinoma treated with NACT followed by interval cytoreduction in one university-affiliated medical center (January 2005 to June 2017). We excluded those who were treated with NACT without any surgical intervention. NACT modifications included delay in treatment, change in chemotherapy, and dose reduction. Demographics, tumor characteristics, surgical outcome, and PFS were compared between patients exposed to NACT treatment modifications and those who received standard treatment.

Results:

Seventy-nine patients met inclusion criteria of whom, 59 patients received standard, nonmodified treatment and 20 patients modified NACT. There were no intergroup differences with respect to age at diagnosis (59.5±11.6 vs. 64.70±8.09, P=0.09) and stage of disease (P=0.13). Radiologic complete response rates (25.0% vs. 32.2%, P=0.545) and optimal cytoreduction rates (75.0% vs. 86.4%, P=0.23) were similar in both treatment groups. Mean PFS (in months) was comparable between patients receiving standard treatment and those who required NACT modifications (18.5 vs. 12.2, P=0.125).

Conclusions:

NACT treatment modifications did not affect surgical outcome and PFS. We conclude that when clinically indicated, dose alteration and scheduling can be implemented without apparent detriment to outcome.
Appendectomy and Risk of Subsequent Diverticular Disease Requiring Hospitalization: A Population-Based Case-Control Study
Authors: Sköldberg Filip , Olén Ola , Ekbom Anders , Schmidt Peter T.
Published: June 2018

BACKGROUND:

Appendicitis and acute diverticulitis share clinical features and are both influenced by genetic and environmental factors. Appendectomy has been positively associated with diverticular disease in hospital-based case–control studies.

OBJECTIVE:

The aim of the present study was to investigate, in a population-based setting, whether appendectomy, with or without appendicitis, is associated with an altered risk of hospitalization with diverticular disease.

DESIGN:

This was a population-based case-control study.

SETTINGS:

The study was based on national healthcare and population registers.

PATIENTS:

We studied 41,988 individuals hospitalized between 2000 and 2010 with a first-time diagnosis of colonic diverticular disease and 413,115 matched control subjects.

MAIN OUTCOME MEASURES:

The association between appendectomy with or without appendicitis and diverticular disease was investigated by conditional logistic regression, including a model adjusting for hospital use.

RESULTS:

A total of 2813 cases (6.7%) and 19,037 controls (4.6%) had a previous record of appendectomy (appendectomy with acute appendicitis: adjusted OR = 1.31 (95% CI, 1.24–1.39); without appendicitis: adjusted OR = 1.30 (95% CI, 1.23–1.38)). Appendectomy was most strongly associated with an increased risk of diverticular disease within 1 year (with appendicitis: adjusted OR = 2.26 (95% CI, 1.61–3.16); without appendicitis: adjusted OR = 3.98 (95% CI, 2.71–5.83)), but the association was still present ≥20 years after appendectomy (with appendicitis: adjusted OR = 1.22 (95% CI, 1.12–1.32); without appendicitis: adjusted OR = 1.19 (95% CI, 1.10–1.28)).

LIMITATIONS:

Detailed clinical information on the cases was not available. There were unmeasured potential confounders, such as smoking and dietary factors.

CONCLUSIONS:

The findings are consistent with a hypothesis of appendectomy causing an increased risk of diverticular disease, for example, by affecting the mucosal immune system or the gut microbiome. However, several other mechanisms may contribute to, or account for, the positive association, including a propensity for abdominal pain increasing the risk of both the exposure and the outcome. SeeVideo Abstractat http://links.lww.com/DCR/A604.
LSD1 Inhibition Prolongs Survival in Mouse Models of MPN by Selectively Targeting the Disease Clone
Authors: Jutzi Jonas S. , Kleppe Maria , Dias Jennifer , Staehle Hans Felix , Shank Kaitlyn , Teruya‐Feldstein Julie , Gambheer Sudheer Madan Mohan , Dierks Christine , Rienhoff Hugh Y. , Levine Ross L. , Pahl Heike L.
Published: June 2018

Supplemental Digital Content is available in the text
Home-based nurse practitioners demonstrate reductions in rehospitalizations and emergency department visits in a clinically complex patient population through an academic–clinical partnership
Authors: Coppa Denise , Winchester Suzy Barcelos , Roberts Mary B.
Published: June 2018

Background and purpose:

The purpose of this pilot study was to describe the impact of one aspect of an academic–clinical partnership that showed how assigning nurse practitioner faculty to deliver home-based primary care services to clinically complex patients would decrease rehospitalizations and emergency department visit rates.

Methods:

Rehospitalizations and emergency department visits of a cohort of 82 patients were recorded from April 15, 2016 to August 25, 2016 and compared with the same cohort during the two pre-home care inception periods (6 months and 1 year) using insurance claims–based data.

Conclusions:

Compared with the 1-year pre-home care inception period, there was a decrease of 23.7% in emergency department visits and 34.9% decrease in rehospitalizations after the implementation of the home-based primary care program and a decrease of 35.6% in emergency department visits and 59.4% decrease in rehospitalizations compared with 6 months of pre-home care inception.

Implications for practice:

Allowing nurse practitioners with full practice authority to deliver home-based primary health care services to homebound, chronically ill, recently discharged, and/or disabled patients can decrease costs and promote optimum health care in this population. In addition, these programs provide valuable learning experiences for nurse practitioner students and their preceptors.
Quantitative Analysis of Surgical Freedom and Area of Exposure in Minimal-Invasive Transcanal Approaches to the Lateral Skull Base
Authors: Anschuetz Lukas , Presutti Livio , Schneider Daniel , Yacoub Abraam , Wimmer Wilhelm , Beck Juergen , Weber Stefan , Caversaccio Marco
Published: June 2018

Hypothesis:

We aim to provide objective data regarding the area of exposure (AOE) and the surgical freedom (SF) offered by the transcanal approaches to the lateral skull base.

Background:

Minimal-invasive transcanal lateral skull base procedures have been recently developed and their clinical feasibility demonstrated. The reduced access size requires careful analysis and selection of suitable cases, qualifying for a minimal-invasive approach.

Methods:

We performed the mentioned approaches in standardized dissection using human whole heads. Surgical freedom is defined as the degree of movement liberty of the surgical instrument at predefined landmarks. We assessed SF at anatomical landmarks throughout the lateral skull base. Moreover, we measured the AOE, defined as the surface on the lateral skull base reached by every approach.

Results:

We performed a total of 48 dissections under stereotactic image guidance in a total of 12 sides. The mean SF was assessed for the inferior petrous apex 602 mm2, for the geniculate ganglion 1,916 mm2, and for the fundus of internal auditory canal 1,337 mm2. The AOE was measured for the infracochlear approach 55 mm2, suprageniculate approach 67 mm2, transpromontorial approach 11 mm2, and for the expanded transpromontorial approach 93 mm2 at the fundus and 108 mm2 at the porus of the internal auditory canal.

Conclusion:

This study provides a quantitative description of minimal-invasive transcanal approaches to the lateral skull base. The AOE offered by the expanded transcanal transpromontorial approach is inferior but comparable to the reported AOE of transmastoidal approaches. The reported objective measurements may provide important information for future preoperative planning and patient counseling.
Compassion Fatigue in Palliative Care Nursing
Authors: Cross Lisa A.
Published: June 2018

The purpose of this review was to define compassion fatigue in the context of palliative care nursing. Compassion fatigue was first introduced as a description for nursing burnout; however, it was not fully described. An initial concept analysis within nursing placed it in terms of a psychological model for secondary traumatic stress disorder, with continual revisions of this application. Palliative care nurses are routinely exposed to pain, trauma, and the suffering they witness by nature of ongoing symptom management and end-of-life care delivery; however, the focus of care is on healthy end-of-life management rather than preservation of life. The literature was reviewed to provide clarification of compassion fatigue for palliative care nurses to assist in future identification and direction in the profession. CINAHL, EBSCO, Journals@Ovid, MEDLINE, PsycINFO, PubMed, and ScienceDirect databases were queried for peer-reviewed literature, and dictionaries were examined for subject-specific definitions. The method that was used was a concept analysis in the tradition of Walker and Avant. A concept definition was proposed for the discipline of palliative care nursing. Identification of compassion fatigue for this profession helps facilitate the recognition of symptoms for a group that deals with patient suffering on a regular basis.
Pathophysiology Review
Authors: Mulkey Malissa A. , Hardin Sonya R. , Olson DaiWai M. , Munro Cindy L.
Published: June 2018

Delirium affects 70% to 80% of intensive care unit patients and is associated with a 10-fold increase in rates of cognitive impairment at discharge and a 3-fold increase in mortality rates. Estimated costs are $152 billion in Medicare charges annually, 17.5 million inpatient days, and 30-day postdischarge costs of $238 726 per patient. Delirium is an acute disorder of attention and global cognitive function characterized by fluctuating symptoms occurring in the face of an underlying organic cause. As patients adapt to physiological stressors, neurotransmitter changes lead to electroencephalogram pattern changes. The ability to compensate for the chemical (neurotransmitter) imbalances is surpassed, causing the behavioral symptomatology we know as delirium. This article seeks to describe the pathophysiology behind the behavior core to the prevention and management of delirium.
Does the Sex Risk Quiz Predict Mycoplasma genitalium Infection in Urban Adolescents and Young Adult Women?
Authors: Ronda Jocelyn , Gaydos Charlotte A. , Perin Jamie , Tabacco Lisa , Coleman Jenell S. , Trent Maria
Published: June 2018

Background

Mycoplasma genitalium (MG) is a common sexually transmitted infection (STI), but there are limited strategies to identify individuals at risk of MG. Previously, a sex risk quiz was used to predict STIs including Chlamydia trachomatis, Neisseria gonorrhoeae, and/or Trichomonas vaginalis. The original quiz categorized individuals 25 years or younger as at risk of STIs, but the Centers for Disease Control and Prevention identifies females younger than 25 years as at risk of STIs. In this study, the quiz was changed to categorize females younger than 25 years as high risk. The objective was to determine if the age-modified risk quiz predicted MG infection.

Methods

A cross-sectional analysis of a prospective longitudinal study was performed including female adolescents and young adults (AYAs) evaluated in multiple outpatient clinics. Participants completed an age-modified risk quiz about sexual practices. Scores ranged from 0 to 10 and were categorized as low risk (0–3), medium risk (4–7), and high risk (8–10) based on the STI prevalence for each score. Vaginal and/or endocervical and/or urine specimens were tested for MG, T. vaginalis, C. trachomatis, and N. gonorrhoeae using the Aptima Gen-Probe nucleic amplification test.

Results

There were 693 participants. Most participants reported having 0 to 1 sexual partners in the last 90 days (91%) and inconsistent condom use (84%). Multivariable logistic regression analysis controlling for race, education, and symptom status demonstrated that a medium-risk score predicted MG infection among AYAs younger than 25 years (adjusted odds ratio, 2.56 [95% confidence interval, 1.06–6.18]).

Conclusion

A risk quiz may be useful during clinical encounters to identify AYA at risk of MG.
Crystal-storing Histiocytosis in the Stomach
Authors: Arnold Christina A. , Frankel Wendy L. , Guo Ling , Krishnan Chandra , Pfeil Sheryl , Schumacher Melinda , Voltaggio Lysandra , Yearsley Martha M. , Chen Wei
Published: June 2018

Crystal-storing histiocytosis (CSH) is an under-recognized entity with a striking association with lymphoproliferative disorders. To study the typical morphologic features of gastric CSH, all lymphomas diagnosed on in-house gastric specimens at The Ohio State University between January 1, 2008 and January 1, 2017 were retrieved. This search yielded 66 specimens from 51 unique patients. All cases were reviewed with CSH identified in 7 stomach biopsies from 4 patients (2 men:2 women; average age, 69 y; range, 56 to 82 y). Endoscopic findings were all abnormal: diffuse nodularity and white discoloration (n=1), patchy nodularity (n=1), and malignant-appearing fundic mass with lymphadenopathy (n=2). We report the typical gastric CSH lesion displays full-thickness expansion of the lamina propria by a lymphohistiocytic infiltrate that distorts the usual gastric glandular architecture. On high power, all cases were defined by the presence of macrophages with abundant eosinophilic cytoplasm containing nonrefractile, nonpolarizable fibrillary cytoplasmic inclusions. Three of the 4 patients had a kappa-restricted lymphoma; the 1 patient with a lambda-restricted lymphoma had the fewest macrophages. Follow-up data were available up to 228 weeks. All 4 patients had persistent/recurrent lymphoma, and 2 patients died of lymphoma-related complications. None of the CSH cases were prospectively recognized as CSH, and 1 case was initially misdiagnosed as a xanthoma. In summary, CSH is an under-recognized lesion historically associated with lymphoproliferative disorders and we found associated with a high mortality in this small series. Since CSH can be so florid as to obscure the concomitant lymphoma, awareness is crucial for accurate diagnosis.
Prepectoral Implant-Based Breast Reconstruction with Postmastectomy Radiation Therapy
Authors: Elswick Sarah M. , Harless Christin A. , Bishop Sarah N. , Schleck Cathy D. , Mandrekar Jay , Reusche Ryan D. , Mutter Robert W. , Boughey Judy C. , Jacobson Steven R. , Lemaine Valerie
Published: June 2018

Background:

Two-stage subpectoral implant-based breast reconstruction is the most common method for breast reconstruction. Recent advances in surgical techniques and technology have made prepectoral implant-based breast reconstruction feasible. There are limited data on outcomes after prepectoral implant-based breast reconstruction and postmastectomy radiation therapy.

Methods:

A retrospective review of consecutive patients undergoing immediate two-stage prepectoral implant-based breast reconstruction with postmastectomy radiation therapy was performed. Outcomes of irradiated breasts were compared with nonirradiated breasts in bilateral cases.

Results:

Ninety-three cases of prepectoral implant-based breast reconstruction in 54 women who underwent immediate two-stage reconstruction (39 bilateral and 15 unilateral) and unilateral postmastectomy radiation therapy were identified. Mean follow-up was 19 months from mastectomy and tissue expander reconstruction and 9 months from implant placement. Crude complication rates in irradiated versus nonirradiated sides were as follows: surgical-site infection, 18.5 percent versus 7.7 percent; seroma, 5.6 percent versus 5.1 percent; mastectomy skin flap necrosis, 1.9 percent versus 2.6 percent; wound dehiscence, 1.9 percent versus 7.7 percent; capsular contracture, 1.9 percent versus 0 percent; hematoma, 1.9 percent versus 2.6 percent; and extrusion, 1.9 percent versus 0 percent. On univariate analysis, there were no risk factors associated with any complication, including radiation therapy, surgical-site infection, unplanned readmissions, and unplanned return to the operating room. To date, reconstruction has been completed in 96 percent of patients, with successful implant-based breast reconstruction in 81 breasts (45 irradiated breasts and 36 nonirradiated breasts).

Conclusions:

Early data of prepectoral implant-based breast reconstruction in patients with postmastectomy radiation therapy show promising results. Postmastectomy radiation therapy should not be an absolute contraindication to prepectoral implant-based breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Evaluation of the Microbotox Technique: An Algorithmic Approach for Lower Face and Neck Rejuvenation and a Crossover Clinical Trial
Authors: Awaida Cyril J. , Jabbour Samer F. , Rayess Youssef A. , El Khoury Joseph S. , Kechichian Elio G. , Nasr Marwan W.
Published: June 2018

Background:

Microbotox consists of the injection of microdroplets of botulinum toxin into the dermis to improve the different lower face and neck aging components. No clinical trial has evaluated its effect on the different face and neck components and no study has compared it to the “Nefertiti lift” procedure.

Methods:

In this crossover study, patients previously treated with the Nefertiti lift were injected using the microbotox technique. Using standardized preinjection and postinjection photographs, the jowls, marionette lines, oral commissures, neck volume, and platysmal bands at maximal contraction and at rest were assessed with validated photonumeric scales. In addition, the overall appearance of the lower face and neck was evaluated by the Investigators and Subjects Global Aesthetic Improvement Score. Pain and patient satisfaction rates were also evaluated.

Results:

Twenty-five of the 30 patients previously treated with the Nefertiti technique were injected with a mean dose of 154 U using the microbotox technique. Platysmal bands with contraction, jowls, and neck volume reached a statistically significant improvement. The microbotox technique improved the jowls and the neck volume more than the Nefertiti technique, whereas the platysmal bands at rest and with contraction were more improved by the Nefertiti technique. One hundred percent of patients were satisfied with both techniques and rated themselves as improved.

Conclusions:

The microbotox technique is a useful, simple, and safe procedure for lower face and neck rejuvenation. It is mainly effective in treating neck and lower face soft-tissue ptosis, in contrast to the Nefertiti technique, which is more effective on platysmal bands.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Topographic Anatomy of the Infraorbital Artery and Its Clinical Implications for Nasolabial Fold Augmentation
Authors: Kim Hong-San , Lee Kyu-Lim , Gil Young-Chun , Hu Kyung-Seok , Tansatit Tanvaa , Kim Hee-Jin
Published: June 2018

Background:

Understanding the topography of the blood vessels distributed around the nasolabial fold region is essential for ensuring the safety of dermal filler injections into the nasolabial fold. The purpose of this study was to provide anatomical information on the infraorbital artery distribution and its relationship with the facial artery for use in clinical procedures involving filler injection during nasolabial fold augmentation.

Methods:

The infraorbital artery was investigated in the nasolabial fold region divided into zones I to XII based on clock-hour meridians centered on the infraorbital foramen. The running layers of the infraorbital artery and infraorbital nerve were also compared in the infraorbital foramen. Changes in the infraorbital artery were observed according to vascular dominance of the facial artery.

Results:

The infraorbital artery was divided into three main branches, palpebral, nasal, and labial infraorbital artery branches in 34.7, 100, and 100 percent of the specimens, respectively; with these branches of palpebral, nasal, and labial infraorbital artery observed most commonly in zones I, V, and VI, respectively. Analysis of the bilateral facial artery topography revealed that its vascular dominance was observed in 19.4 percent. The infraorbital artery was thicker and had a wider distribution on the nondominant side of the facial artery, whereas the nasal infraorbital nerve anastomosed with the facial artery in the lateral nasal region in 57.1 percent.

Conclusion:

Investigating and verifying the vascular structure regarding its interactions with the facial artery and infraorbital artery will provide critical information to physicians performing facial surgery and cosmetic procedures.
Laparoscopic Repair of Diaphragmatic Eventeration in Adults: Plication With Mesh Repair
Authors: Wang Zhijiang , Ye Qinghuang , Chen Yan , Zhu Jinhui
Published: June 2018

Background:

Diaphragmatic eventeration is a rare congenital anomaly consisting of defect of diaphragm muscular development, which can be diagnosed with chest radiography and clinical evaluation. Diaphragmatic plication is a well-established treatment for diaphragmatic eventeration, which can be done through the thoracic or abdominal route, and minimally invasive became the trend in recent years.

Methods:

The study retrospectively analyzed 3 cases of diaphragmatic eventeration with the procedure of laparoscopic diaphragmatic plication with mesh repair from August 2016 to April 2017. A detailed review of medical records and the perioperative data including patient characteristics, operative details, and postoperative hospital stay was conducted.

Results:

Laparoscopic diaphragmatic plication with mesh repair for diaphragmatic eventeration was successfully completed for 3 patients. The mean operation time was 125 minutes (range, 120 to 135 min), and the mean blood loss was 13.3 mL (range, 10 to 15 mL). The postoperative intercostal neuralgia was detailed evaluated and intervention as necessary. All patients were followed up at 1, 3, and 6 months after procedure, and the recoveries were uneventful.

Conclusions:

Laparoscopic diaphragmatic plication with mesh repair provides a new operative view, which may be a safe and feasible alternative in the surgical management of diaphragmatic eventeration.
Repurposing the quinoline antibiotic nitroxoline to treat infections caused by the brain-eating amoebaBalamuthia mandrillaris
Authors: Laurie Matthew T. , White Corin V. , Retallack Hanna , Wu Wesley , Moser Matthew S. , Sakanari Judy , Ang Kenny , Wilson Christopher , Arkin Michelle R. , DeRisi Joseph L.
Published: June 2018

Balamuthia mandrillarisis a pathogenic free-living amoeba that causes a rare but almost always fatal infection of the central nervous system called granulomatous amoebic encephalitis (GAE). Two distinct forms ofB. mandrillaris– a proliferative trophozoite form and a non-proliferative cyst form, which is highly resistant to harsh physical and chemical conditions – have been isolated from environmental samples worldwide and are both observed in infected tissue. Patients suffering from GAE are typically treated with aggressive and prolonged multi-drug regimens often including the antimicrobial agents miltefosine and pentamidine isethionate. However, survival rates remain low and studies evaluating the susceptibility ofB. mandrillaristo these compounds and other potential therapeutics are limited. To address the need for more effective treatments, we screened 2,177 clinically-approved compounds forin vitroactivity againstB. mandrillaris. The quinoline antibiotic nitroxoline, which has safely been used in humans to treat urinary tract infections, was identified as a lead compound. We show that nitroxoline inhibits both trophozoites and cysts at low micromolar concentrations, which are within a physiologically relevant range. We compare thein vitroefficacy of nitroxoline to drugs currently used in the standard of care for GAE and find that nitroxoline is the most potent and selective inhibitor ofB. mandrillaristested. Furthermore, we demonstrate that nitroxoline preventsB. mandrillaris-mediateddestruction of host cells in cultured fibroblast and primary brain explant models also at physiologically relevant concentrations. Together, our findings indicate that nitroxoline is a promising candidate for repurposing as a novel treatment ofB. mandrillarisinfections.

Importance

Balamuthia mandrillarisis responsible for hundreds of reported cases of amoebic encephalitis, the majority of which have been fatal. Despite being an exceptionally deadly pathogen,B. mandrillarisis understudied, leaving many open questions regarding epidemiology, diagnosis, and treatment. Due to the lack of effective drugs to fightB. mandrillarisinfections, mortality rates remain high even for patients receiving intensive care. This study addresses the need for new anti-amoebic drugs using a high-throughput screening approach to identify novelB. mandrillarisinhibitors. The most promising candidate identified was the quinoline antibiotic nitroxoline, which has a long history of safe use in humans. We show that nitroxoline killsB. mandrillarisat physiologically relevant concentrations and exhibits greater potency and selectivity than drugs commonly used in the current standard of care. The findings we present demonstrate the potential of nitroxoline to be an important new tool in the treatment of life threateningB. mandrillarisinfections.
Correction of respiratory artifacts in MRI head motion estimates
Authors: Fair Damien A. , Miranda-Dominguez Oscar , Snyder Abraham Z. , Perrone Anders , Earl Eric A. , Van Andrew N. , Koller Jonathan M. , Feczko Eric , Klein Rachel L. , Mirro Amy E. , Hampton Jacqueline M. , Adeyemo Babatunde , Laumann Timothy O. , Gratton Caterina , Greene Deanna J. , Schlaggar Bradley L. , Hagler Don , Watts Richard , Garavan Hugh , Barch Deanna M. , Nigg Joel T. , Petersen Steven E. , Dale Anders , Feldstein-Ewing Sarah W. , Nagel Bonnie J. , Dosenbach Nico U.F.
Published: June 2018

Head motion represents one of the greatest technical obstacles for brain MRI. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, this estimation may be corrupted by factitious effects owing to main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and a comparison ‘single-shot’ dataset from Oregon Health & Science University. We show unequivocally that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with degraded quality of functional MRI. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects. Subsequently, we demonstrate that utilizing this filter improves post-processing data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package.
Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development
Authors: Oatley Morgan , Bölükbasi Özge Vargel , Svensson Valentine , Shvartsman Maya , Ganter Kerstin , Zirngibl Katharina , Pavlovich Polina V. , Milchevskaya Vladislava , Foteva Vladimira , Natarajan Kedar N. , Baying Bianka , Benes Vladimir , Patil Kiran R. , Teichmann Sarah A. , Lancrin Christophe
Published: June 2018

The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening we identified CD44 as a new marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta gonad mesonephros (AGM) region. This allowed us to provide a very detailed phenotypical and transcriptional profile for haemogenic endothelial cells, characterising them with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists (Smad6, Smad7 and Bmper) and a downregulation of genes related to glycolysis and the TCA cycle. Moreover, we demonstrated that by inhibiting the interaction between CD44 and its ligand hyaluronan we could block EHT, identifying a new regulator of HSPC development.
Novel Wolbachia strains in Anopheles malaria vectors from Sub-Saharan Africa
Authors: Jeffries Claire L , Lawrence Gena G , Golovko George , Kristan Mojca , Orsborne James , Spence Kirstin , Hurn Eliot , Bandibabone Janvier , Tantely Michael L , Raharimalala Fara N , Keita Kalil , Camara Denka , Barry Yaya , Wat’senga Francis , Manzambi Emile Z , Afrane Yaw A , Mohammed Abdul R , Abeku Tarekegn A. , Hegde Shivanand , Khanipov Kamil , Pimenova Maria , Fofanov Yuriy , Boyer Sébastien , Irish Seth R , Hughes Grant L , Walker Thomas
Published: June 2018

Anopheles (An.) mosquitoes contain bacteria that can influence Plasmodium parasites. Wolbachia, a common insect endosymbiont, has historically been considered absent from Anopheles but has recently been found in An. gambiae populations. Here, we assessed a range of Anopheles species from five malaria-endemic countries for Wolbachia and Plasmodium infection. Strikingly, we found Wolbachia infections in An. coluzzii, An. gambiae s.s, An. arabiensis, An. moucheti and An. species ‘A’ increasing the number of Anopheles species known to be naturally infected by this endosymbiont. Molecular analysis suggests the presence of phylogenetically diverse novel strains, while qPCR and 16S rRNA sequencing indicates that Wolbachia is the dominant member of the microbiota in An. moucheti and An. species ‘A’. We found no evidence of Wolbachia/Asaia co-infections, and presence of these endosymbionts did not have significant effects on malaria prevalence. We discuss the importance of novel Wolbachia strains in Anopheles and potential implications for disease control.
Parkour LIMS: facilitating high-quality sample preparation in next generation sequencing
Authors: Anatskiy E. , Ryan D.P. , Grüning B. , Arrigoni L. , Manke T. , Bönisch U.
Published: June 2018

This paper presents Parkour, a software package for sample processing and quality management of next generation sequencing data and samples. Starting with user requests, Parkour allows tracking and assessing samples based on predefined quality criteria through different stages of the sample preparation workflow. Ideally suited for academic core laboratories, the software aims to maximize efficiency and reduce turnaround time by intelligent sample grouping and a clear assignment of staff to work units. Tools for automated invoicing, interactive statistics on facility usage and simple report generation minimize administrative tasks. Provided as a web application, Parkour is a convenient tool for both deep sequencing service users and laboratory personal. A set of web APIs allow coordinated information sharing with local and remote bioinformaticians. The flexible structure allows workflow customization and simple addition of new features as well as the expansion to other domains.

Availability and implementation

The code and documentation are available at https://github.com/maxplanck-ie/parkour

Contact

boenisch@ie-freiburg.mpg.de
TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing
Authors: Beaulieu-Laroche L. , Christin M. , Donoghue AM , Agosti F. , Yousefpour N. , Petitjean H. , Davidova A. , Stanton C. , Khan U. , Dietz C. , Faure E. , Fatima T. , MacPherson A. , Ribeiro-Da-Silva A. , Bourinet E. , Blunck R. , Sharif-Naeini R.
Published: June 2018

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying several physiological functions such as touch and pain sensing, hearing and proprioception. This process is carried out by specialized mechanosensitive ion channels whose identities have been discovered for most functions except pain sensing. Here we report the identification of TACAN (Tmem120A), an essential subunit of the mechanosensitive ion channel responsible for sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically-evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, knocking down TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to mechanical but not to thermal pain stimuli, without affecting the sensitivity to touch stimuli. We propose that TACAN is a pore-forming subunit of the mechanosensitive ion channel responsible for sensing mechanical pain.
GenotypeTensors: Efficient Neural Network Genotype Callers
Authors: Cohen Joshua , Simi Manuele , Campagne Fabien
Published: June 2018

We studied the problem of calling genotypes using neural networks. A machine learning approach to calling genotypes requires a training set, an approach to convert genomic sites into tensors and robust model development and evaluation protocols. We discuss each of these components of our approach and compare four types of neural network training protocols, two fully supervised and two semi-supervised approaches. Semi-supervised approaches use unlabeled data to supplement limited quantities of labeled data. Random hyper-parameter searches identified highly performing models that reach indel F1 of 99.4% on a chromosomes 20, 21, 22 and X of NA12878/HG001. We further validate these models by evaluating performance on HG002, an independent sample used in the PrecisionFDA challenge. We apply GenotypeTensors to evaluate the impact of (1) training with small datasets, (2) training models only with sites inside confidence regions, or (3) training with improved true label annotations. A PyTorch open-source implementation of GenotypeTensors is available at https://github.com/CampagneLaboratory/GenotypeTensors. DNANexus cloud applications are provided to help process new datasets both to train model or call genotypes with trained models.
Comparison of trimethoprim-sulfamethoxazole versus ciprofloxacin monotherapy in Stenotrophomonas maltophilia bloodstream infections in children
Authors: Aksay Ahu , Devrim İlker , Katipoğlu Nagehan , Bayram Nuri , Arslanoglu Sertaç , Çallkavur Şebnem , Gülfidan Gamze , Ceylan Gökhan , Ağın Hasan
Published: June 2018

Treatment of invasive infections caused by Stenotothromhomas maltophilia is difficult as the bacterium is frequently resistant to a wide range of commonly used antimicrobials. The aim of this retrospective study was to evaluate effectiveness of treatment with ciprofloxacin monotherapy compared to trimethoprim-sulfamethoxazole monotherapy in patients with S. maltophilia infections. We evaluated 50 patients with S. maltophilia bloodstream infections who had received monotherapy with trimethoprim-sulfamethoxazole or ciprofloxacin. Twenty-five patients (50%) received trimethoprim-sulfamethoxazole, and 25 patients (50%) received ciprofloxacin. Thirty-six (72%) patients were in the intensive care unit. All of the patients had at least one indwelling devices and approximately 25% patients had immunosuppression. Ciprofloxacin had the same clinical outcome and mortality as trimethoprim-sulfamethoxazole for the treatment of S. maltophilia bacteremia. In our study; side-effects ratio were not statistically different between ciprofloxacin and trimethoprim-sulfamethoxazole group. Ciprofloxacin could be an alternative drug of choice for treating S. maltophilia infections especially in premature infans in stead of trimethoprim-sulfamethoxazole.
The key lethal effect existed in the antibacterial behavior of short, medium, and long chain fatty acid monoglycerides onEscherichia coli
Authors: Zhang Song , Xiong Jian , Lou Wenyong , Ning Zhengxiang , Zhang Denghui , Yang Jiguo
Published: June 2018

Monoglyceride is an amphiphilic molecule with promising antimicrobial activity for bacteria; however, the key lethal effect in its antibacterial behavior was still unknown. In the study, monobutyrate (MB), monolaurate (ML), monomyristate (MM) were selected to represent the short, medium, and long chain monoglycerides to compare their inhibitory effect againstEscherichia coli, and a new dose-dependent inhibitory mechanism was proposed by the key lethal effect. The minimal inhibitory concentration and antibacterial curve showed a huge diversity existed in biology activity of MB, ML and MM. The results in scanning electron microscopy and flow cytometry assay indicated that the interference level of MB on cell membrane was obviously weaker than that of ML and MM, while the latter two had similar performance in increasing cell permeability at low doses. The results presented in UV-Vis spectroscopy, cell cycle and biomacromolecules synthesis inhibition assay showed that the cell cycle ofEscherichia coliwas obviously affected by three monoglycerides at doses near MIC, which was therefore regarded as the key lethal effect. The reason for the better biological activity of MM than ML was the stronger interference ability on bacterial cell cycle. In addition, an expanded antibacterial mode was raised that cell permeability increase at low doses was antimicrobial basis, cell cycle arrest at medium doses played the key lethal effect, and cell lysis at high doses was the result of combined action.
Contextual influence on confidence judgments in human reinforcement learning
Authors: Lebreton Maël , Bacily Karin , Palminteri Stefano , Engelmann Jan B.
Published: June 2018

The ability to correctly estimate the probability of one’s choices being correct is fundamental to optimally re-evaluate previous choices or to arbitrate between different decision strategies. Experimental evidence nonetheless suggests that this metacognitive process -referred to as a confidence judgment-is susceptible to numerous biases. We investigate the effect of outcome valence (gains or losses) on confidence while participants learned stimulus-outcome associations by trial-and-error. In two experiments, we demonstrate that participants are more confident in their choices when learning to seek gains compared to avoiding losses. Importantly, these differences in confidence were observed despite objectively equal choice difficulty and similar observed performance between those two contexts. Using computational modelling, we show that this bias is driven by the context-value, a dynamically updated estimate of the average expected-value of choice options that has previously been demonstrated to be necessary to explain equal performance in the gain and loss domain. The biasing effect of context-value on confidence, also recently observed in the context of incentivized perceptual decision-making, is therefore domain-general, with likely important functional consequences.
Adversarial childhood events are associated with Sudden Infant Death Syndrome (SIDS): an ecological study
Authors: Elhaik Eran
Published: June 2018

Sudden Infant Death Syndrome (SIDS) is the most common cause of postneonatal infant death. Theallostatic load hypothesisposits that SIDS is the result of perinatal cumulative painful, stressful, or traumatic exposures that tax neonatal regulatory systems. To test it, we explored the relationships between SIDS and two common stressors, male neonatal circumcision (MNC) and prematurity, using latitudinal data from 15 countries and over 40 US states during the years 1999-2016. We used linear regression analyses and likelihood ratio tests to calculate the association between SIDS and the stressors. SIDS prevalence was significantly and positively correlated with MNC and prematurity rates. MNC explained 14.2% of the variability of SIDS’s male bias in the US, reminiscent of the Jewish myth of Lilith, the killer of infant males. Combined, the stressors increased the likelihood of SIDS. Ecological analyses are useful to generate hypotheses but cannot provide strong evidence of causality. Biological plausibility is provided by a growing body of experimental and clinical evidence linking adversary preterm and early-life events with SIDS. Together with historical evidence, our findings emphasize the necessity of cohort studies that consider these environmental stressors with the aim of improving the identification of at-risk infants and reducing infant mortality.
metagenomeFeatures: An R package for working with 16S rRNA reference databases and marker-gene survey feature data
Authors: Olson Nathan D. , Shah Nidhi , Kancherla Jayaram , Wagner Justin , Paulson Joseph N. , Corrada-Bravo Hector
Published: June 2018

We developed themetagenomeFeaturesR Bioconductor package along with annotation packages for the three primary 16S rRNA databases (Greengenes, RDP, and SILVA) to facilitate working with 16S rRNA sequence databases and marker-gene survey feature data. ThemetagenomeFeaturespackage defines two classes,MgDbfor working with 16S rRNA sequence databases, andmgFeaturesfor working with marker-gene survey feature data. The associated annotation packages provide a consistent interface to the different 16S rRNA databases facilitating database comparison and exploration. ThemgFeaturesrepresents a crucial step in the development of a common data structure for working with 16S marker-gene survey data in R.

Availability

https://bioconductor.org/packages/release/bioc/html/metagenomeFeatures.html

Contact

nolson@nist.gov