bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do You Let Your Child Know about the Plan?
Authors: Lebowitz Eli R.
Published: October 2020

This chapter highlights the importance of telling the child with anxiety about the plan. The child will be surprised and confused by the change in the parents’ behavior if they do not tell the child beforehand. Describing the plan to the child will also help the parents to stay firm and committed to implementing the plan. Moreover, telling the child about the change the parents are going to make not only respects the child as a person, one who is going to be directly affected by the change, but it also gives the child an opportunity to offer feedback and input. The child is probably going to be less opposed to the plan and the whole process may be much easier. The chapter then details how parents can let their child know about the plan in a supportive way, expressing both acceptance and confidence. The message that the parents give to the child to let them know about the plan for reducing accommodation has a few simple goals. It should let the child know why the parents are planning to reduce the accommodation, and it should let the child know the what, when, who, and how and how much of the plan.
Troubleshooting—Dealing with Difficulties in Working with Your Partner
Authors: Lebowitz Eli R.
Published: October 2020

This chapter suggests some solutions for when the parents do not agree with each other or have difficulty working cooperatively together. If the parents are having a hard time talking about the child’s anxiety, they can try to set aside a time to talk about the issue when neither of them is under pressure nor feeling frustrated and upset. Talking about the problem may raise some negative feelings, but the parents have a better chance of having a productive conversation if they start out feeling calm. The parents should also try to stay away from unhelpful blaming and shaming; even self-blame can make it harder for parents to work together productively. It is best to keep the conversations about how to help the anxious child focused on the issue of the anxiety. If the parents can put other things aside and just focus on the one issue, it may be easier to come up with a plan for that one specific thing. The chapter also offers some additional tools and strategies for improving cooperation between parents. Ultimately, the parents should respect each other’s opinions and decisions.
Work and Class Among Women with Serious Mental Illness
Authors: Mizock Lauren , Carr Erika
Published: October 2020

This chapter presents the literature on women with serious mental illness and the intersecting experiences of work, class, poverty, and homelessness. This chapter includes literature that sheds light on challenges related to work, class, and poverty among this unique population, including a review of data that will explore these intersecting experiences. Research is presented on the mental health challenges for women in work. The effects of a serious mental illness for these women are explored in terms of how they can interfere with pursuit of work and financial wellness. The resilience of this group is discussed with regard to carving out meaningful work. This chapter includes several case narratives, a clinical strategies list, discussion questions, activities, and a clinical worksheet (“Work and Class Worksheet”).
Preventing Retraumatization of Women with Serious Mental Illness
Authors: Mizock Lauren , Carr Erika
Published: October 2020

This chapter discusses the increased rates of victimization among women with serious mental illness. The concept of retraumatization in mental health services is explained and an overview of the literature in this area is provided. Factors that contribute to retraumatization of women with serious mental illness in psychotherapy are discussed. Feminist frameworks and evidence-based treatments for trauma that are consistent with feminist therapy are explored. Clinical strategies for promoting an atmosphere of trust and safety for trauma survivors are provided. This chapter also includes case narratives, a clinical strategies list, discussion questions, activities, and a clinical worksheet (“Preventing Retraumatization Worksheet”).
3D NLTE spectral line formation of lithium in late-type stars
Authors: Wang Ella Xi , Nordlander Thomas , Asplund Martin , Amarsi Anish M , Lind Karin , Zhou Yixiao
Published: October 2020

Accurately known stellar lithium abundances may be used to shed light on a variety of astrophysical phenomena such as big bang nucleosynthesis, radial migration, ages of stars and stellar clusters, and planet engulfment events. We present a grid of synthetic lithium spectra that are computed in non-local thermodynamic equilibrium (NLTE) across the stagger grid of three-dimensional (3D) hydrodynamic stellar atmosphere models. This grid covers three Li lines at 610.4, 670.8, and 812.6 nm for stellar parameters representative of FGK-type dwarfs and giants, spanning Teff = 4000–7000 K, log g = 1.5–5.0, $[\rm {Fe}/\rm {H}]= -4.0$–0.5, and A(Li) = −0.5–4.0. We find that our abundance corrections are up to 0.15 dex more negative than in previous work, due to a previously overlooked NLTE effect of blocking of UV lithium lines by background opacities, which has important implications for a wide range of science cases. We derive a new 3D NLTE solar abundance of A(Li) = 0.96 ± 0.05, which is 0.09 dex lower than the commonly used value. We make our grids of synthetic spectra and abundance corrections publicly available through the breidablik package. This package includes methods for accurately interpolating our grid to arbitrary stellar parameters through methods based on Kriging (Gaussian process regression) for line profiles, and multilayer perceptrons (a class of fully connected feedforward neural networks) for NLTE corrections and 3D NLTE abundances from equivalent widths, achieving interpolation errors of the order of 0.01 dex.
Re-observing the NLS1 galaxy RE J1034+396 – II. New insights on the soft X-ray excess, QPO, and the analogy with GRS 1915+105
Authors: Jin Chichuan , Done Chris , Ward Martin
Published: October 2020

The active galactic nucleus (AGN) RE J1034+396 displays the most significant X-ray quasi-periodic oscillation (QPO) detected so far. We perform a detailed spectral-timing analysis of our recent simultaneous XMM–Newton, NuSTAR, and Swift observations. We present the energy dependence of the QPO’s frequency, rms, coherence, and phase lag, and model them together with the time-averaged spectra. Our study shows that four components are required to fit all the spectra. These components include an inner disc component (diskbb), two warm corona components (CompTT-1 and CompTT-2), and a hot corona component (nthComp). We find that diskbb, CompTT-2 (the hotter but less luminous component), and nthComp all contain the QPO signal, while CompTT-1 only exhibits stochastic variability. By fitting the lag spectrum, we find that the QPO in diskbb leads CompTT-2 by 679 s, and CompTT-2 leads nthComp by 180 s. By only varying the normalizations, these components can also produce good fits to the time-averaged and variability spectra obtained from previous observations when QPOs were present and absent. Our multiwavelength study shows that the detectability of the QPO does not depend on the contemporaneous mass accretion rate. We do not detect a significant Iron K α emission line, or any significant reflection hump. Finally, we show that the rms and lag spectra in the latest observation are very similar to the 67-Hz QPO observed in the micro-quasar GRS 1915+105. These new results support the physical analogy between these two sources. We speculate that the QPO in both sources is due to the expansion/contraction of the vertical structure in the inner disc.
Reithrodontomys mexicanus(Rodentia: Cricetidae)
Authors: Martínez-Borrego Daily , Arellano Elizabeth , González-Cózatl Francisco X , Rogers Duke S
Published: October 2020

Reithrodontomys mexicanus (Saussure, 1860) is a cricetid rodent commonly called the Mexican harvest mouse and is one of 24 recognized species in the genus. It has grooved upper incisors distinctive of Reithrodontomys, and a medium to relatively large size, with tail longer than head and body; dorsal pelage varies from brown to cinnamon orange. It is distributed from Mexico to Nicaragua and in the northwestern region of South America. It occupies different habitats including humid pine-oak forests, cloud forests, and deciduous forests at elevations from about 1,000 to 3,800 m. R. mexicanus is listed as “Least Concern” by the International Union for Conservation of Nature and Natural Resources, although information about population size throughout its distribution range is unknown.
Calculating the net clinical benefit in neuro-oncology clinical trials using two methods: quality-adjusted survival effect sizes and joint modeling
Authors: Coomans Marijke B , Dirven Linda , Aaronson Neil K , Baumert Brigitta G , van den Bent Martin , Bottomley Andrew , Brandes Alba A , Chinot Olivier , Coens Corneel , Gorlia Thierry , Herrlinger Ulrich , Keime-Guibert Florence , Malmström Annika , Martinelli Francesca , Sloan Jeff A , Stupp Roger , Talacchi Andrea , Weller Michael , Wick Wolfgang , Reijneveld Jaap C , Taphoorn Martin J B
Published: October 2020

Background

Two methods combining survival and health-related quality of life (HRQoL) data in glioma trials to calculate the “net clinical benefit” were evaluated: Quality-adjusted effect sizes (QASES) and joint modeling (JM).

Methods

The net clinical benefit in two trials was calculated as proof of concept for other trials. With the QASES method, effect sizes for differences in progression-free survival (PFS) or overall survival (OS) and HRQoL between the experimental arm and standard treatment arm were calculated, while the relative emphasis placed on survival/HRQoL varied. JM allows simultaneous modeling of HRQoL and OS/PFS.

Results

In the EORTC 26951 trial, combined radiochemotherapy significantly prolonged OS (difference 11.7 months), but also resulted in more patients experiencing clinically relevant worsening (≥10 points) in appetite loss and nausea/vomiting shortly after treatment. Using QASES, the survival benefit of additional procarbazine, lomustine, and vincristine (PCV) decreased from 42.3 months to 29.5 and 28.2 months when accounting for appetite loss and nausea/vomiting, respectively. JM analyses resulted in a loss of the beneficial effect of additional PCV between 13% and 24% when adjusting for different HRQoL parameters. The EORTC 22033 trial showed no significant PFS difference between radiotherapy or temozolomide alone (46 vs 39 months), nor clinically relevant differences in HRQoL. JM analyses also showed no significant association between PFS and HRQoL scales/items, whereas QASES showed that temozolomide alone was more favorable when considering symptom burden (47–49 instead of 39 months).

Conclusions

Both methods resulted in different outcomes, but adjusting for the impact of treatment on HRQoL resulted in theoretically reduced survival benefits.
The glutamine antagonist prodrug JHU-083 slows malignant glioma growth and disrupts mTOR signaling
Authors: Yamashita Alex Shimura , da Costa Rosa Marina , Stumpo Vittorio , Rais Rana , Slusher Barbara S , Riggins Gregory J
Published: October 2020

Background

Metabolic reprogramming is a common feature in cancer, and it is critical to facilitate cancer cell growth. Isocitrate Dehydrogenase 1/2 (IDH1 and IDH2) mutations (IDHmut) are the most common genetic alteration in glioma grade II and III and secondary glioblastoma and these mutations increase reliance on glutamine metabolism, suggesting a potential vulnerability. In this study, we tested the hypothesis that the brain penetrant glutamine antagonist prodrug JHU-083 reduces glioma cell growth.

Material and Methods

We performed cell growth, cell cycle, and protein expression in glutamine deprived or Glutaminase (GLS) gene silenced glioma cells. We tested the effect of JHU-083 on cell proliferation, metabolism, and mTOR signaling in cancer cell lines. An orthotopic IDH1R132H glioma model was used to test the efficacy of JHU-083 in vivo.

Results

Glutamine deprivation and GLS gene silencing reduced glioma cell proliferation in vitro in glioma cells. JHU-083 reduced glioma cell growth in vitro, modulated cell metabolism, and disrupted mTOR signaling and downregulated Cyclin D1 protein expression, through a mechanism independent of TSC2 modulation and glutaminolysis. IDH1R132H isogenic cells preferentially reduced cell growth and mTOR signaling downregulation. In addition, guanine supplementation partially rescued IDHmut glioma cell growth, mTOR signaling, and Cyclin D1 protein expression in vitro. Finally, JHU-083 extended survival in an intracranial IDH1 mut glioma model and reduced intracranial pS6 protein expression.

Conclusion

Targeting glutamine metabolism with JHU-083 showed efficacy in preclinical models of IDHmut glioma and measurably decreased mTOR signaling.
Efficacy and costs of a workplace wellness programme
Authors: Rezai R , SantaBarbara N , Almirol E , Shedd K , Terry E , Park M , Comulada W S
Published: October 2020

Background

Research investigating the efficacy of workplace wellness programmes to promote exercise, and by extension, reduce obesity and increase productivity has proliferated in recent years. Although preliminary work is encouraging, more work is needed.

Aims

To evaluate the effects and overall cost of a workplace exercise programme on multiple physical outcomes, including body mass index, aerobic fitness and muscular fitness.

Methods

Data from the Bruin Health Improvement Programme .5 (BHIP) between August 2013 and July 2018 were analysed. BHIP is a 12-week workplace wellness programme that assesses multiple areas of physical and mental health. For this study, changes in weight, waist-to-hip ratio, aerobic fitness and muscular endurance were analysed using paired samples t-tests and chi-squared tests. Using results from a prior analysis of Medical Expenditure Panel Survey, the estimated medical expenditure savings associated with weight loss were also analysed.

Results

A total of 518 participants (84% female) took part in the BHIP programme (mean age = 41 years, SD = 1.17). There were significant decreases in all anthropometric indices and significant increases in all fitness outcomes (P < 0.01) from baseline to follow-up. Estimated programme cost per participant, per session was $473 US Dollars (USD), and weight loss is estimated to reduce annual medical care costs by ~$2200 USD.

Conclusions

Results showed significant improvements in all physical outcomes of interest. Additionally, there appears to be an inverse relationship between improvements in employee health and employer healthcare costs. Strengths, limitations and future directions are discussed.
Slithering Through the Bone Marrow: Loiasis in a Patient With Human T-Cell Leukemia Virus-1-Associated Adult T-Cell Lymphoma
Authors: Boodman Carl , Marko Daniel , Keynan Yoav
Published: October 2020

Loiasis is a filarial disease endemic to areas of Central and West Africa. We present a case of Loa loa microfilaremia in a patient with HTLV-1-related adult T-cell lymphoma. This case may suggest the possible role of cellular immunity in controlling microfilaria burden.
Mechanisms Activating Latent Functions of PIP Aquaporin Water Channels via the Interaction between PIP1 and PIP2 Proteins
Authors: Shibasaka Mineo , Horie Tomoaki , Katsuhara Maki
Published: October 2020

Plant plasma membrane-type plasma membrane intrinsic protein (PIP) aquaporins are classified into two groups, PIP1s and PIP2s. In this study, we focused on HvPIP1;2, a PIP1 in barley (Hordeum vulgare), to dissect the molecular mechanisms that evoke HvPIP1-mediated water transport. No HvPIP1;2 protein was localized to the plasma membrane when expressed alone in Xenopus laevis oocytes. By contrast, a chimeric HvPIP1;2 protein (HvPIP1;2_24NC), in which the N- and C-terminal regions were replaced with the corresponding regions from HvPIP2;4, was found to localize to the plasma membrane of oocytes. However, HvPIP1;2_24NC showed no water transport activity in swelling assays. These results suggested that the terminal regions of PIP2 proteins direct PIP proteins to the plasma membrane, but the relocalization of PIP1 proteins was not sufficient to PIP1s functionality as a water channel in a membrane. A single amino acid replacement of threonine by methionine in HvPIP2;4 (HvPIP2;4T229M) abolished water transport activity. Co-expression of HvPIP1;2_24NC either with HvPIP2;4_12NC or with HvPIP2;4TM_12NC, in which the N- and C-terminal regions were replaced with the corresponding regions of HvPIP1;2, increased the water transport activity in oocytes. These data provided evidence that the HvPIP1;2 molecule has own water transport activity and an interaction with the middle part of the HvPIP2;4 protein (except for the N- and C-termini) is required for HvPIP1;2 functionality as a water channel. This molecular mechanism could be applied to other PIP1s and PIP2s in addition to the known mechanism that the terminal regions of some PIP2s lead some PIP1s to the plasma membrane.
User Interface and Firsthand Experience in Retail Investing
Authors: Liao Li , Wang Zhengwei , Xiang Jia , Yan Hongjun , Yang Jun
Published: October 2020

Using data from a major online peer-to-peer lending platform, we document that, due to time pressure, investors appear to focus on interest rates and only partially account for credit ratings in their decisions. The effect is stronger for mobile-based investors than for PC-based ones. Our evidence suggests that this variation is caused by the difference in information content on the interfaces rather than differences in the devices’ physical attributes per se. Investors improve their decisions by slowing down and paying more attention to credit ratings after experiencing a loan default firsthand, but not after observing others experiencing defaults.
Association of proton pump inhibitor and histamine H2-receptor antagonists with restless legs syndrome
Authors: Earley Eric J , Didriksen Maria , Spencer Bryan R , Kiss Joseph E , Erikstrup Christian , Pedersen Ole B , Sørensen Erik , Burgdorf Kristoffer S , Kleinman Steven H , Mast Alan E , Busch Michael P , Ullum Henrik , Page Grier P
Published: October 2020

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge–Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H2A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13–1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03–1.95; p = 0.03) and H2A (OR = 1.56; CI, 1.10–2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H2As (OR = 1.29; CI, 1.20–1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17–1.38; p < 0.001), but not H2As alone (OR = 1.18; CI, 0.92–1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H2A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H2A in populations at particular risk for RLS.
Evaluation of oral citrulline administration as a mitigation strategy for fescue toxicosis in sheep
Authors: Greene Maslyn A , Klotz James L , Goodman Jack P , May John B , Harlow Brittany E , Baldwin William S , Strickland James R , Britt Jessica L , Schrick F Neal , Duckett Susan K
Published: October 2020

Gestating ewes consuming ergot alkaloids, from endophyte-infected (E+) tall fescue seed, suffer from intrauterine growth restriction and produce smaller lambs. Arginine (Arg) supplementation has been shown to increase birth weight and oral citrulline (Cit) administration is reported to increase arginine concentrations. Two experiments were conducted to: 1) evaluate if oral supplementation with Cit or water, to ewes consuming E+ fescue seed, increases lamb birth weight and 2) determine the effectiveness of Cit and citrulline:malate as an oral drench and elevating circulating levels of Cit to determine levels and dose frequency. In experiment 1, gestating Suffolk ewes (n = 10) were assigned to one of two treatments [oral drench of citrulline–malate 2:1 (CITM; 81 mg/kg/d of citrulline) or water (TOX)] to start on d 86 of gestation and continued until parturition. Ewes on CITM treatment had decreased (P < 0.05) plasma Arg and Cit concentrations during gestation. At birth, lambs from CITM ewes had reduced (P < 0.05) crude fat and total fat but did not differ (P > 0.05) in birth weight from lambs born to TOX ewes. In experiment 2, nonpregnant Suffolk ewes (n = 3) were assigned to either oral citrulline (CIT; 81 mg/kg/d), citrulline–malate 2:1 (CITM; 81 mg/kg/d of citrulline), or water (CON) drench in a Latin Square design for a treatment period of 4 d with a washout period of 3 d. On d 4, blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 18 h post drench. Oral drenching of CIT and CITM increased (P < 0.0001) Cit concentrations within 2 h and levels remained elevated for 6 h. Apparent half-life of elimination for CIT and CITM were 8.484 and 10.392 h, respectively. Our results show that lamb birth weight was not altered with a single oral drench of citrulline–malate; however, lamb body composition was altered. The level and frequency of citrulline dosing may need to be greater in order to observe consistent elevation of Cit/Arg concentrations to determine its effectiveness in mitigating fescue toxicosis.
Targeting sedentary behavior as a feasible health strategy during COVID-19
Authors: Zieff Gabriel , Bates Lauren C , Kerr Zachary Y , Moore Justin B , Hanson Erik D , Battaglini Claudio , Stoner Lee
Published: October 2020

Sedentary behavior is associated with poor physical and mental health. Targeting sedentary behavior is a simple strategy that may help counter physical and mental health concerns associated with COVID-19-related social restrictions. Of course, traditional strategies such as achieving optimal exercise and physical activity levels are also important and should be recommended. However, even under normal circumstances, the difficulty in promoting lasting exercise habits at multiple levels (e.g. individual, environment, policy) are well documented, and chances of maintaining or improving these factors is now even lower. Thus, relative to other lifestyle behaviors – sedentary behavior may be more amenable to change. Moreover, reducing sedentary behavior may be less susceptible to influence from factors associated with health disparities such as age, race, and socio-economic status compared to exercise or physical activity. Sedentary behavior is a feasible health strategy that should be targeted during COVID-19.
The Complexity of the NICU-to-Home Experience for Adolescent Mothers
Authors: Orr Elizabeth , Ballantyne Marilyn , Gonzalez Andrea , Jack Susan M.
Published: October 2020

Quality care for individuals and families during periods of transition is one of the major issues facing health care systems and providers today. The transition-home from the neonatal intensive care unit (NICU) as experienced by adolescent mothers is poorly understood—placing young mothers and their infants at risk of poor outcomes following NICU discharge. Meleis' Transitions Theory offers a unique theoretical perspective for understanding this transition experience and also serves to highlight the complexity of the NICU-to-home transition for this population of young mothers that is not currently elucidated in the literature.
Dexmedetomidine for prevention of postoperative delirium in older adults undergoing oesophagectomy with total intravenous anaesthesia
Authors: Hu Jun , Zhu Mudan , Gao Zongbin , Zhao Shihao , Feng Xiaomei , Chen Jinbao , Zhang Ye , Maze Mervyn
Published: October 2020

BACKGROUND

Dexmedetomidine is known to be a sedative. Recent studies suggest that administration of dexmedetomidine can prevent postoperative delirium (POD) which has been confirmed as a common complication after major surgery. However, its effects in patients undergoing oesophagectomy are scarce.

OBJECTIVE

To investigate the efficacy and safety of dexmedetomidine in reducing POD in elderly patients after transthoracic oesophagectomy with total intravenous anaesthesia (TIVA).

DESIGN

A randomised, double-blind, placebo-controlled trial.

SETTING

Single-centre, tertiary care hospital, November 2016 to September 2018.

PATIENTS

Eligible patients (n = 177) undergoing transthoracic oesophagectomy were randomly assigned to receive total intravenous anaesthesia (TIVA, n = 87) or dexmedetomidine with TIVA (DEX-TIVA, n = 90).

INTERVENTIONS

Patients receiving DEX-TIVA received a loading dose of dexmedetomidine (0.4 μg kg−1), over 15 min, followed by a continuous infusion at a rate of 0.1 μg kg−1 h−1 until 1 h before the end of surgery. Patients receiving TIVA received physiological saline with a similar infusion rate protocol.

OUTCOME MEASURES

The primary outcome was the incidence of POD. The secondary endpoints were the incidence of emergence agitation, serum interleukin-6 (IL-6) levels and haemodynamic profile.

RESULTS

All randomised patients were included with planned intention-to-treat analyses for POD. Delirium occurred in 15 (16.7%) of 90 cases given dexmedetomidine, and in 32 (36.8%) of 87 cases given saline (P = 0.0036). The DEX-TIVA group showed less frequent emergence agitation than the TIVA group (22.1 vs. 48.0%, P = 0.0058). The incremental change in surgery-induced IL-6 levels was greater in the TIVA group than DEX-TIVA group (P < 0.0001).

CONCLUSION

Adding peri-operative dexmedetomidine to a total intravenous anaesthetic safely reduces POD and emergence agitation in elderly patients undergoing open transthoracic oesophagectomy. These benefits were associated with a postoperative reduction in circulating levels of the pro-inflammatory cytokine IL-6 and stabilisation of the haemodynamic profile.

TRIAL REGISTRATION

Chinese Clinical Trials Register Identifier: ChiCTR-IPR-17010881.
Refractive enhancements for residual refractive error after cataract surgery
Authors: Moshirfar Majid , Thomson Andrew C. , Thomson Robert J. , Martheswaran Tanisha , McCabe Shannon E.
Published: October 2020

Purpose of review

Advances in cataract surgery have allowed surgeons to achieve superior refractive outcomes but have also led to higher patient expectations. Despite ever-evolving technology, residual refractive errors still occur. Postcataract refractive enhancements may be required to deliver satisfactory visual outcomes. This review aims to discuss the potential causes of residual refractive errors and the various enhancement modalities to correct them.

Recent findings

A thorough preoperative workup to detect and address underlying pathologic causes of impaired vision should be performed prior to enhancement or corrective procedures. Corneal-based procedures are the safest and most accurate methods of correcting mild cases of residual refractive error. Hyperopic, high myopic, and high astigmatic errors are best managed with lens-based enhancements. Piggyback intraocular lenses (IOLs) are safer and more effective compared with IOL exchange. Toric IOL rotation and IOL exchange are ideally performed in the early postoperative period.

A multitude of options exist for effective correction of residual refractive errors. The choice on how to best manage these patients depends on many factors such as the cause of refractive error, type of IOL used, ocular comorbidities, and patient preference.
Stylet Slow-pull Versus Standard Suction for Endoscopic Ultrasound-guided Fine-needle Aspiration/Biopsy of Pancreatic Solid Masses
Authors: Wang Jing , Xu Hongwei , Xu Changqin , Feng Yuemin , Zhang Xiaohua , Zhao Shulei
Published: October 2020

Background and Study Aim:

There is limited evidence on the diagnostic performance of the stylet slow-pull (SP) method for endoscopic ultrasound-guided fine-needle aspiration/biopsy. The aim of this study was to compare the SP method with standard suction (SS) for endoscopic ultrasound-guided fine-needle aspiration/biopsy of solid pancreatic masses.

Methods:

A computerized bibliographic search of the main databases, including PubMed, EMBASE, Cochrane Library, and Science Citation Index, was performed through February 2020. The main outcome measurements were diagnostic accuracy, cellularity, low blood contamination, adequate core tissue acquisition, and technical success rate.

Results:

Eleven studies (including 6 randomized trials) were included, with a total of 504 patients who underwent SP and 551 who underwent SS. Diagnostic accuracy was significantly superior in the SP group, compared with the SS group [odds ratio (OR)=1.60; 95% confidence interval (CI), 1.14-2.26]. The SP group had higher pooled rates of low blood contamination (OR=1.93; 95% CI, 1.29-2.87) and adequate core tissue acquisition (OR=1.91; 95% CI, 1.11-3.26) than the SS group. There was no significant difference between groups in the adequacy of cellularity (OR=0.99; 95% CI, 0.63-1.57; P=0.98) or technical success rate (OR=0.38; 95% CI, 0.13-1.15; P=0.09).

Conclusions:

The authors provide evidence that SP is superior to SS in diagnostic accuracy, low blood contamination, and adequate core tissue acquisition, without reducing adequacy of cellularity or technical success rate.
Efficacy of i3.1 Probiotic on Improvement of Lactose Intolerance Symptoms
Authors: Cano-Contreras Ana D. , Minero Alfaro Isidro J. , Medina López Víctor M. , Amieva Balmori Mercedes , Remes Troche José M. , Espadaler Mazo Jordi , Perez Lopez Nuria
Published: October 2020

Goal:

The aim of this study was to assess the efficacy of probiotic i3.1 in improving lactose intolerance symptoms compared with placebo after 8 weeks of treatment.

Background:

Probiotics are promising strategies to prevent and improve lactose intolerance symptoms, but previous studies have provided conflicting results.

Materials and Methods:

This randomized, prospective, placebo-controlled study was conducted at the Hospital Juárez de México. We recruited adult patients with lactose intolerance confirmed by a lactose hydrogen breath test (LHBT) ≥20 parts per million (ppm) and a lactose intolerance symptom score ≥6 both upon lactose challenge. We compared the change from baseline in the scores of a validated symptom questionnaire and the LHBT after 8 weeks of probiotic or placebo treatment.

Results:

We included 48 patients: 33 receiving the probiotic and 15 receiving placebo (2:1 randomization). Demographic characteristics were homogeneous between groups. The reduction in total symptom score after a lactose challenge was significantly higher in the probiotic group versus the placebo group (−5.11 vs. −1.00; P<0.001). All the subscores significantly decreased from baseline in the probiotic group, except for vomiting, with significant differences between the probiotic and placebo groups for abdominal pain (P=0.045) and flatulence (P=0.004). The area under the curve of the LHBT was significantly reduced from baseline in the probiotic group (P=0.019), but differences between groups were not significant (P=0.621). Adverse events were mild without differences between groups, and no serious adverse event was registered.

Conclusion:

The i3.1 probiotic was safe and efficacious in reducing lactose intolerance symptoms in patients with lactose intolerance, but did not change the LHBT.
Allogeneic Hematopoietic Stem Cell Transplant Offer Good Outcomes in Pediatric Aplastic Anemia: Experience From Developing World
Authors: Sachdev Mansi , Bansal Minakshi , Chakraborty Sohini , Jain Sachin , Bhargava Rahul , Dua Vikas
Published: October 2020

Between 2014 and 2020, 31 patients with severe aplastic anemia (SAA) underwent full match allogeneic hematopoietic stem cell transplantation at our center. Of the 31 patients with SAA, 19 had acquired aplastic anemia, 2 had Diamond Blackfan anemia and 10 had Fanconi anemia. Donors were either matched sibling (n=29), related donors (n=2), or unrelated donors (n=3). Peripheral blood stem cells were the graft source in all the cases except 1. Fludarabine-based reduced intensity conditioning was used in all except for patients with a diagnosis of Diamond Blackfan anemia. All patients except 1 achieved hematologic recovery in the form of neutrophil engraftment at 13 days (range, 9 to 17), whereas platelet engraftment occurred at 14 days (range, 10 to 18). Graft versus host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate ±antithymocyte globulin (horse/rabbit). Acute GvHD developed in 12.9% patients, whereas no patients developed chronic GvHD till the time of last follow-up. The 2-year overall survival for the entire cohort was 93.21±4.6%. In patients with SAA, allogeneic stem cell transplant using fludarabine-based conditioning regimens are very well tolerated and have excellent outcomes in a full match setting.
Current Approach to the Evaluation and Management of Incomplete Kawasaki Disease in the Emergency Department
Authors: Morishita Kimberly A. , Goldman Ran D.
Published: October 2020

Kawasaki disease (KD) is one of the most common vasculitides of childhood and frequently presents to the emergency department. Although the diagnosis of KD is based on clinical criteria, children who do not fulfill the criteria but have sufficient supportive features of KD are diagnosed as having incomplete KD and warrant the same course of therapy as children with classic KD. The diagnosis of incomplete KD is challenging and requires a high index of suspicion. The purpose of this article is to review presenting features of incomplete KD and the diagnostic approach and management of children in the emergency department.
Identifying Regions of Greatest Need for Ending the HIV Epidemic: A Plan for America
Authors: Moore Mia , Boily Marie-Claude , Mitchell Kate M. , Donnell Deborah D. , Cohen Myron S. , Dimitrov Dobromir T.
Published: October 2020

Background:

In the 2019 State of the Union Address, President Trump announced a plan for “Ending the HIV Epidemic” in the United States, with a goal to reduce new HIV infections by 90% by 2030. Phase I of the plan set an intermediate goal of a 75% reduction within 5 years, focusing on select states and counties.

Methods:

We assessed the feasibility of the first phase of the plan by estimating the fraction of HIV diagnoses that occur within the targeted region, using a statistical model to predict new HIV cases in each county. We suggested new areas that should be added to the current plan, prioritizing by both a “Density Metric” of new HIV cases and a “Gap Metric” quantifying shortcomings in antiretroviral therapy and pre-exposure prophylaxis uptake.

Results:

We found the current plan targets less than 60% of new diagnoses. The plan should be expanded to Puerto Rico, Florida, Georgia, Louisiana, and Maryland as well as parts of New York, North Carolina, Texas, and Virginia, areas which were prioritized by both metrics.

Conclusion:

Many of the highest priority areas, both by density of HIV cases and by lack of viral suppression and pre-exposure prophylaxis use, were not covered by the original plan, particularly in the South. The current plan to end the HIV epidemic must be expanded to these areas to feasibly allow for a 75% reduction in new HIV cases within 5 years.
Embedding Evidence-Based Practices to Address Literacy in School-Based Speech–Language Therapy
Authors: Tambyraja Sherine R. , Schmitt Mary Beth
Published: October 2020

Children with language impairment (LI) are at an elevated risk for reading difficulties, particularly if their language difficulties are present at the time of formal schooling entry. Learning to read is heavily dependent on linguistic knowledge, specifically phonological knowledge for word decoding and language comprehension for reading comprehension. Thus, speech–language pathologists (SLPs) are well suited to address both the language and literacy difficulties that children with LI may encounter. However, evidence suggests that children's literacy skills are rarely targets of intervention even in school-based settings. This article reviews evidence for why literacy should be addressed within the context of therapy, the positive effects that literacy interventions confer, and an examination of current practices regarding treating reading as a therapy target. The article concludes with suggestions for perspectives and approaches that may address the challenges and barriers faced by school-based SLPs, who should embed evidence-based literacy interventions for children with LI in their therapeutic activities.
How Healthcare Congestion Increases Covid-19 Mortality: Evidence from Lombardy, Italy*
Authors: Ciminelli Gabriele , Garcia-Mandicó Sílvia
Published: October 2020

Background

The Covid-19 pandemic has caused generous and well-developed healthcare systems to collapse. This paper quantifies how much system congestion may have increased mortality rates, using distance to the ICU as a proxy for access to emergency care.

Methods

We match daily death registry data for almost 1,500 municipalities in Lombardy, Italy, to data on geographical location of all ICU beds in the region. We then analyze how system congestion increases mortality in municipalities that are far from the ICU through a differences-in-differences regression model.

Findings

We find that Covid-19 mortality is up to 60% higher in the average municipality – which is 15 minutes driving away from the closest ICU – than in a municipality with an ICU in town. This difference is larger in areas and in days characterized by an abnormal number of calls to the emergency line.

Interpretation

We interpret these results as suggesting that a sudden surge of critical patients may have congested the healthcare system, forcing emergency medical services to prioritize patients in the most proximate communities in order to maximize the number of lives saved. Through some back-of-the-envelope calculations, we estimate that Lombardy’s death toll from the first Covid-19 outbreak could have been 25% lower had all municipalities had ready access to the ICU. Drawing a lesson from Lombardy’s tale, governments should strengthen the emergency care response and palliate geographical inequalities to ensure that everyone in need can receive critical care on time during new outbreaks.

Funding

No funding.
Mice with Induced Pulmonary Comorbidities Display Severe Lung Inflammation and Mortality following Exposure to SARS-CoV-2
Authors: Falach Reut , Bar-On Liat , Lazar Shlomi , Kadar Tamar , Mazor Ohad , Aftalion Moshe , Gur David , Shifman Ohad , Israeli Ofir , Cohen-Gihon Inbar , Zaide Galia , Gutman Hila , Evgy Yentl , Vagima Yaron , Makdasi Efi , Stein Dana , Rosenfeld Ronit , Alcalay Ron , Zahavy Eran , Levy Haim , Glinert Itai , Ben-Shmuel Amir , Israely Tomer , Melamed Sharon , Politi Boaz , Achdout Hagit , Yitzhaki Shmuel , Kronman Chanoch , Sabo Tamar
Published: October 2020

Severe manifestations of COVID-19 are mostly restricted to people with comorbidities. Here we report that induced mild pulmonary morbidities render SARS-CoV-2-refractive CD-1 mice to be susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low-doses of the acute-lung-injury stimulants bleomycin or ricin caused a severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates of >50%. Further studies revealed markedly higher levels of viral RNA in the lungs, heart and serum of low-dose-ricin pretreated, as compared to non-pretreated mice. Notably, the deleterious effects of SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or monoclonal antibodies generated against SARS-CoV-2 RBD. Thus, viral cell entry in the sensitized mice seems to involve viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. In summary, we present a novel mice-based animal model for the study of comorbidity-dependent severe COVID-19.
Isolation and Characterization of L-Glutaminase producing Bacteria
Authors: Saleem Rabia , Ahmed Safia
Published: October 2020

Being a significant protein L-glutaminases discovers potential applications in various divisions running from nourishment industry to restorative and cure. It is generally disseminated in microbes, actinomycetes, yeast and organisms. Glutaminase is the principal enzyme that changes glutamine to glutamate. The samples were gathered from soil of Taxila, Wah Cantt and Quetta, Pakistan for the isolation of glutaminase producing bacteria. After primary screening, subordinate screening was done which includes multiple testification such as purification, observation of morphological characters and biochemical testing of bacterial strains along with 16S rRNA sequence homology testing. Five bacterial strains were selected showing glutaminase positive test in screening, enzyme production via fermentation and enzymatic and protein assays. Taxonomical characterization of the isolates identified them asBacillus subtilisU1,Achromobacter xylosoxidansG1,Bacillus subtilisQ2,Stenotrophomonas maltophiliaU3 andAlcaligenes faecalisS3. The optimization of different effectors such as incubation time, inducers, carbon source, pH, and nitrogen source were also put under consideration. There was slight difference among incubation of bacterial culture, overall, 36 hours of incubation time was the best for glutaminase production by all the strains. Optimal pH was around 9 inAchromobacter xylosoxidansG1 andAlcaligenes faecalisS3, pH 6 inBacillus subtilisU1, pH 8 inStenotrophomonas maltophiliaU3, pH 6-8 inBacillus subtilisQ2. Best glutaminase production was obtained at 37°C byBacillus subtilisU1andBacillus subtilisQ2, 30°C forAchromobacter xylosoxidansG1,Stenotrophomonas maltophiliaU3 and 25°C byAlcaligenes faecalisS3. The carbon sources put fluctuated effects on activity of enzyme in such a way that glucose was the best carbon source forBacillus subtilisU1andBacillus subtilisQ2, Sorbitol forAchromobacter xylosoxidansG1 andAlcaligenes faecalisS3 while xylose was the best forStenotrophomonas maltophiliaU3. Yeast extract and Trypton were among good nitrogen sources forAchromobacter xylosoxidansG1 and ofBacillus subtilisU1 respectively. Glutamine was the best inducer forBacillus subtilisQ2,Alcaligenes faecalisS3 andStenotrophomonas maltophiliaU3, while lysine forAchromobacter xylosoxidansG1 and glycine act as good inducer in case ofBacillus subtilisU1. After implementation of optimal conditions microbial L-glutaminase production can be achieved and the bacterial isolates have a great potential for production of glutaminase enzyme and their applications.
Predicting modular functions and neural coding of behavior from a synaptic wiring diagram
Authors: Vishwanathan Ashwin , Ramirez Alexandro D. , Wu Jingpeng , Sood Alex , Yang Runzhe , Kemnitz Nico , Ih Dodam , Turner Nicholas , Lee Kisuk , Tartavull Ignacio , Silversmith William M. , Jordan Chris S. , David Celia , Bland Doug , Goldman Mark S. , Aksay Emre R. F. , Seung H. Sebastian ,   the Eyewirers
Published: October 2020

How much can connectomes with synaptic resolution help us understand brain function? An optimistic view is that a connectome is a major determinant of brain function and a key substrate for simulating a brain. Here we investigate the explanatory power of connectomics using a wiring diagram reconstructed from a larval zebrafish brainstem. We identify modules of strongly connected neurons that turn out to be specialized for different behavioral functions, the control of eye and body movements. We then build a neural network model using a synaptic weight matrix based on the reconstructed wiring diagram. This leads to predictions that statistically match the neural coding of eye position as observed by calcium imaging. Our work shows the promise of connectome-based brain modeling to yield experimentally testable predictions of neural activity and behavior, as well as mechanistic explanations of low-dimensional neural dynamics, a widely observed phenomenon in nervous systems.
Crispr2vec: Machine Learning Model Predicts Off-Target Cuts of CRISPR systems
Authors: Trivedi Tara Basu , Boger Ron , Kamath Govinda M. , Evangelopoulos Georgios , Cate Jamie , Doudna Jennifer , Hidary Jack
Published: October 2020

1

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-Cas systems have revolutionized gene editing, with applications in therapeutics, diagnostics, agriculture, and developing disease models. However, CRISPR-Cas suffers from off-target effects — unintended genetic modifications in the genome that arise from its use. In this work, we present crispr2vec: a deep metric learning approach for embedding CRISPR single guide RNA (sgRNA) sequences and predicting off-target cuts. Given a fixed target sequence, we show that our learned embedding yields a faithful representation of potential off-targets. We present a new triplet sampling strategy specifically for CRISPR sequences that improves the quality of our embedding. We show the resulting embedding generalizes across different off-target cut detection assays. Finally, we demonstrate the superiority of our deep metric learning method in its ability to predict off-target cuts compared to previous literature in cross fold validation across different datasets for both seen and unseen sgRNAs.
Chloroplast quality control pathways are dependent on plastid DNA synthesis and nucleotides provided by cytidine triphosphate synthase two
Authors: Alamdari Kamran , Fisher Karen E. , Welsh David W. , Rai Snigdha , Palos Kyle R. , Nelson Andrew D. L. , Woodson Jesse D.
Published: October 2020

Reactive oxygen species (ROS) produced in chloroplasts cause oxidative damage, but also signal to initiate chloroplast quality control pathways, cell death, and gene expression. The mechanisms behind these signals are largely unknown.

TheArabidopsis thaliana plastid ferrochelatase two(fc2) mutant produces the ROS singlet oxygen in chloroplasts that activates such signaling pathways. Here we mapped onefc2suppressor mutation toCYTIDINE TRIPHOSPHATE SYNTHASE TWO(CTPS2), which encodes one of five enzymes inArabidopsisnecessary forde novocytoplasmic CTP (and dCTP) synthesis.

Thectps2mutation reduces chloroplast transcripts and DNA content without similarly affecting mitochondria. Chloroplast nucleic acid content and singlet oxygen signaling are restored by exogenous feeding of the dCTP precursor deoxycytidine, suggestingctps2blocks signaling by limiting nucleotides for chloroplast genome maintenance.

An investigation of CTPS orthologs in Brassicaceae showed CTPS2 is a member of an ancient lineage distinct from CTPS3. Complementation studies confirmed this analysis; CTPS3 was unable to compensate for CTPS2 function in providing nucleotides for chloroplast DNA and signaling.

Our studies link cytoplasmic nucleotide metabolism with chloroplast quality control pathways. Such a connection is achieved by a conserved clade of CTPS enzymes that may have evolved specialized functions in providing nucleotides to specific subcellular compartments.