bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report on Colloidal Nodular Goiter
Authors: Sharma Bindu , Sexena Reteka
Published: June 2019

Goiter refers to an enlarged thyroid gland which can be caused by a number of factors such as biosynthetic defects, iodine deficiency, autoimmune disease and nodular diseases. A case of a woman with colloidal nodular goiter treated successfully with Homoeopathy is reported here. Her thyroid profile was within normal range, and fine-needle aspiration cytology was clearly suggestive of colloidal nodular goiter. She was treated with homoeopathic medicines following holistic concepts of homoeopathy, and the result was significant reduction in size of thyroid nodule. Lycopodium initiated the action, and Sulphur potentiated the cure.
Homoeopathy in Cancer Pain Palliation and End of Life with Future Perspectives
Authors: Sachdeva Jyoti , Dey Joy Kumar
Published: June 2019

Pain is a common companion of people receiving palliative care in cancer and at the end of life. Cancer pain is multifactorial and complex. Its impact can be devastating, with increased morbidity and poor quality of life, if not treated adequately. Cancer pain management is a challenging task both due to disease process and due to treatment-related side effects; therefore, it requires a holistic approach which can be covered by homoeopathic remedies. The purpose of this article is to enlighten the scope and future perspective of homoeopathy in pain palliative care and at the end of life. This article summarises the need of multidimensional approach towards the cancer pain palliation and at the end of life in which homoeopathy may play a key role of supportive care. Homoeopathy may become a valuable treatment in palliative care to provide relief and comfort to the dying patient, and therefore the fear of death may reduce and the family may be better prepared for the bereavement. Homoeopathy can well integrate with standard oncologic cares to improve patient outcome including symptom burden, quality of life and end-of-life outcomes, all achieved with low associated costs.
Case Report on Hyperuricemia Presenting as One-Sided Disease
Authors: Bala Renu , Srivastava Amit
Published: June 2019

Hyperuricemia is very common, and a prevalence of up to 15 to 20% has been reported in population-based studies. Although hyperuricemia is not a disease, if uric acid levels remain high, over time they can lead to several diseases. Hyperuricemia is the central risk factor for gout and is a key component of the metabolic syndrome. The case illustrated here is of hyperuricemia with only symptom of pain in the joints, large as well as small, mainly the shoulder joints, knee joints, ankle joints and interphalangeal joints for 2 years without any associated complaint. The case is a one-sided disease, that is, disease in which symptoms are very few, which got cleared up with antisycotic drugs. Thuja and Medorrhinum prescribed in the beginning of the case on the guidelines for one-sided diseases mentioned in Organon of Medicine and later responded very well to Bryonia alba in higher potencies to lower the level of serum uric acid significantly along with long-lasting improvement in signs and symptoms of the patient.
Case Report of an Abscess in a Bitch Healed with Alternative Medicine
Authors: Macías Álvaro Millán
Published: June 2019

The most widespread treatment for infected wounds, that enjoys the trust of the medical community, is antibiotherapy. After this, surgery can be considered, if there are recurrences or serious risks for the patient's health. The following reported case aims to demonstrate the effectiveness of natural therapies in the resolution of infections that occur with suppuration. A half-blood old bitch developed an encapsulated abscess on the back of her neck. An exhaustive clinical examination was done to diagnose an immune deficiency. This can explain the failure of antibiotics prescribed by another practitioner. The combination of acupuncture, homeopathy, and phytotherapy solved the problem satisfactorily in one month. This integrative approach is based on the complementation between Chinese traditional medicine and homeopathic medicine.
Homoeopathic Awareness among the Tribal Population Visiting a Homoeopathic Hospital set up in West Bengal
Authors: Mukherjee Anupam , Banerjee Ayushman , Das Kaushik D.
Published: June 2019

Background Tribal population in India had been known to depend on traditional tribal medicines for long to cure their ailments. With the development of health care facilities and spread of AYUSH system:of late many tribal people are seeking homoeopathic treatment. More than half of the tribal population of West Bengal are concentrated in the South western part of the state that covers the districts of Paschim Medinipur, Purulia, and Bankura. Midnapore Homoeopathic Medical College and Hospital being located in the same region gets a good number of tribal patients seeking homoeopathic care.

Objective To assess the level of homoeopathic awareness and the reasons for their preference to homoeopathic system.

Methods A cross sectional survey was conducted in the outpatient department of Midnapore Homeopathic Medical College and Hospital, Government of West Bengal, India from January 2016 to June 2016 on adult tribal population using a self-administered questionnaire.

Results The survey performed on tribal patients reflected the level of homoeopathic awareness, prevalence of disease, socio-demographic data, and health status of the tribal population. The positive effect with homoeopathic treatment also became evident in the study.

Conclusion A favorable attitude toward homoeopathy among the tribal population was obtained. However, some wrong notions about the mode also emerged in the study. In this respect, the authors felt the need on arrangement of homoeopathic health camps and distribution of homoeopathic awareness materials in tribal language to improve the scenario.
Clinical Evaluation of Homoeopathic Medicines in Benign Prostatic Hyperplasia
Authors: Gupta Neeraj , Singh Rahul , Saxena R.K.
Published: June 2019

Background Symptomatic benign prostatic hyperplasia (BPH) is a common condition in elderly men and has a significant impact on their daily lives. Surgical procedures are currently used for the conventional treatment for BPH; but they have been associated with clinically significant adverse effects in patients.

Objectives The main purpose of this article is to evaluate the role of homoeopathic medicines for the treatment of BPH.

Materials and Methods Clinically diagnosed 30 subjects of BPH were given homoeopathy treatment and followed up for a period of 1 year. Homoeopathic medicines were prescribed to the subjects according to the principles of homoeopathy. Effects of homoeopathic medicines were analysed periodically by American Urological Association score (AUA score) and ultrasonography.

Results Marked amelioration of symptoms and reduction in size of prostate gland in BPH subjects were observed after homoeopathic treatment when analysed by AUA score and ultrasonography. There was marked reduction in various symptoms of BPH like nocturia, straining, incomplete sensation after urination, interrupted flow of urination with dribbling of urine and urgency significantly from 21.60 ± 4.64 units to 12.23 ± 3.68, that is, ∼57% reduction in symptoms of obstruction of bladder problem. The reduction was statistically significant (p = 0.001). However, transabdominal pelvic ultrasonic scan did not show statistically significant results.

Conclusion Homoeopathic medicines can prove to be an alternative treatment of BPH.
Copper toxicity to Folsomia candida in different soils: a comparison between nano and conventional formulations
Authors: Neves Joana , Cardoso Diogo N. , Malheiro Catarina , Kah Melanie , Soares Amadeu M. V. M. , Wrona Frederick J. , Loureiro Susana
Published: June 2019

Environmental contextNanotechnology has great potential for managing agricultural plant disease. This study compares effects of various nano and conventional copper formulations on Collembola Folsomia candida, a model arthropod often used to test soil pollutants. Although toxicity varied between formulations, with a nanopesticide showing one of the highest toxicities, the differences were mainly due to the active copper compound rather than its nano formulation.
AbstractNanotechnology has recently become a major asset in agricultural practices owing to the improvement and provision of solutions for plant disease management, especially in the form of nanopesticides. These products are considered as one of the main direct sources of nanomaterials in terrestrial ecosystems, and for that reason, it is essential to understand and evaluate their behaviour and toxicity in the environment. In addition, the panoply of similar compounds makes it difficult to accurately evaluate if different formulations may induce different effects on non-target organisms. We aim to compare the toxicity and bioavailability of different copper formulations (nano and non-nano) applied to the soil using the model organism Folsomia candida. Reproduction tests were performed in two different soils (Lufa 2.1 and 2.2) with two equilibrium times after spiking (0 and 48h). Depending on the copper form present in the formulation, the half maximal effective concentration (EC50) values of the non-nano pesticides varied from 274mgCukg−1 in Champion® to 3030mgCukg−1 in Cupravit® in Lufa 2.2 and 48h equilibrium. The nano formulation displayed one of the highest toxicities to collembolans, with an EC50 of 156mgCukg−1. Regarding the soil type, a higher toxicity in Lufa 2.1 was observed probably related to the soil characteristics, namely lower pH and lower organic content, which increase the metal solubility and consequently the bioavailability. The only exception was the nanopesticide Kocide 3000®, whose toxicity was higher in Lufa 2.2. This study emphasises the importance of understanding the links between metal bioavailability and toxicity to support the more robust environmental risk assessment of different Cu fungicide formulations.
Determining the sensitivity of grassland area burned to climate variation in Xilingol, China, with an autoregressive distributed lag approach
Authors: Shabbir Ali Hassan , Zhang Jiquan , Liu Xingpeng , Lutz James A. , Valencia Carlos , Johnston James D.
Published: June 2019

We examined the relationship between climate variables and grassland area burned in Xilingol, China, from 2001 to 2014 using an autoregressive distributed lag (ARDL) model, and describe the application of this econometric method to studies of climate influences on wildland fire. We show that there is a stationary linear combination of non-stationary climate time series (cointegration) that can be used to reliably estimate the influence of different climate signals on area burned. Our model shows a strong relationship between maximum temperature and grassland area burned. Mean monthly wind speed and monthly hours of sunlight were also strongly associated with area burned, whereas minimum temperature and precipitation were not. Some climate variables like wind speed had significant immediate effects on area burned, the strength of which varied over the 2001–14 observation period (in econometrics terms, a ‘short-run’ effect). The relationship between temperature and area burned exhibited a steady-state or ‘long-run’ relationship. We analysed three different periods (2001–05, 2006–10 and 2011–14) to illustrate how the effects of climate on area burned vary over time. These results should be helpful in estimating the potential impact of changing climate on the eastern Eurasian Steppe.
Acute effects of kinesio taping on muscular strength and endurance parameters of the finger flexors in sport climbing: A randomised, controlled crossover trial
Authors: Limmer Mirjam , Buck Susanne , de Marées Markus , Roth Ralf
Published: June 2019

Kinesio taping (KT) is a commonly used intervention in sports and, recently, KT has become popular among athletes competing in sport climbing and bouldering events. However, evidence on the effect of KT on grip strength and endurance is still controversial. Therefore, the purpose of this study was to evaluate immediate effects of KT on muscular strength and endurance of the finger flexor muscles in sport climbers. Twenty recreationally‐trained active sport climbers (10 men, 10 women) aged 28.5 ± 10.6 years performed one familiarisation trial and subsequently, in a randomised crossover design, two test trials either with (TAPE) or without (CONTROL) KT over the finger flexor muscles. Test trials consisted of three performance measurements (hand grip strength and endurance, finger hang, and lap climbing) at intervals of 48 h in a randomised order. We observed no significant differences in the parameters of hand grip peak force, fatigue index, finger hang time, lap climbing distance and time, or maximum blood lactate values after lap climbing between the TAPE and CONTROL trials (p > 0.05). The participants’ climbing ability was significantly correlated with the intra‐individual performance changes between the TAPE and CONTROL conditions for the fatigue index (r = −0.598, p = 0.005), but not in any of the other performance‐related parameters. Therefore, KT over the finger flexor muscles neither enhanced hand grip strength and endurance nor the sport climbing performance parameters of finger hang, lap climbing distance and time, and maximum blood lactate values after lap climbing.
Postural stability
Authors: Ibrahim Iman , da Silva Sabrina Daniela , Segal Bernard , Zeitouni Anthony
Published: June 2019

Purpose:

Dizziness is the most common complaint of patients over 65 years consulting a physician. Presbyacusis affects 65% of Canadians aging 70–79. The inner ear is responsible for both hearing and postural stability. However, the interactions between auditory information and the maintenance of postural balance have not been widely studied. The aim of this study is to evaluate and compare the effect of auditory input on postural stability for normal hearing subjects versus hearing-aid users.

Methods:

The effect of auditory input on postural stability was assessed with and without earplugs in normal subjects, and in adult hearing users with and without hearing aids. Balance tests (Romberg on foam and Tandem stance) were performed in the presence of a point-source of noise in both groups.

Results:

Normal individuals’ balance performance was not affected by the absence of auditory input. However, hearing aid users had significantly better balance with hearing aids on for the Romberg test (v = 36, p = .014), and for the Tandem test (v = 44, p = .012).

Conclusion:

Auditory input does not seem to have an effect on postural stability in normal hearing individuals. However, hearing aid users had a significant improvement in the presence of an auditory input.
A qualitative exploration of the experiences of community dwelling older adults with sensory impairment/s receiving polypharmacy on their pharmaceutical care journey
Authors: Smith Annetta , Macaden Leah , Kroll Thilo , Alhusein Nour , Taylor Andrea , Killick Kirsty , Stoddart Kathleen , Watson Margaret
Published: June 2019

Background

Most developed countries have increasing numbers of community dwelling older people with both multi-morbidity and sensory impairment that includes visual, hearing or dual impairment. Older people with sensory impairment are more likely to have chronic health conditions and to be in receipt of polypharmacy (>4 medicines). It is important to understand their experience of pharmaceutical care provision to facilitate a safe, appropriate and person centred approach.

Aim

this study explored the pharmaceutical care experiences and perspectives of older people with sensory impairment receiving polypharmacy.

Design and setting

exploratory qualitative study with semi-structured telephone or face-to-face interviews with community dwelling older adults with sensory impairment receiving polypharmacy in Scotland in 2016.

Methods

in total, 23 interviews were conducted with older people from seven of the 14 Scottish Health Board areas.

Subjects

over half the participants (n = 12) had dual sensory impairment, six had visual impairment and five had hearing impairment.

Results

three overarching themes were identified reflecting different stages of participants’ pharmaceutical care journey: ordering and collection of prescriptions; medicine storage; and administration. At each stage of their journey, participants identified barriers and facilitators associated with their pharmaceutical care.

Conclusions

this is the first comprehensive, in-depth exploration of the pharmaceutical care journey needs of older people with sensory impairment. As the number of community dwelling older people with sensory impairment and polypharmacy increases there is a requirement to identify challenges experienced by this population and offer solutions for safe and effective pharmaceutical care provision.
Decreased vigilance or habituation to humans? Mechanisms on increased boldness in urban animals
Authors: Uchida Kenta , Suzuki Kei K , Shimamoto Tatsuki , Yanagawa Hisashi , Koizumi Itsuro
Published: June 2019

Increased boldness is one of the most prevalent behavioral modifications seen in urban animals and is thought to be a coping response to anthropogenic environmental alterations. Most previous studies have shown enhanced boldness manifested as changes in responses to humans approaching, such as reductions in flight initiation distance (FID). However, this includes two confounding factors related to “boldness,” that is, reduction of vigilance and habituation to humans. Confounding these totally different processes could lead to our misunderstanding of urban adaptation and how to properly manage urban wildlife. Here, we propose a simple framework to separate the two processes using two flight distance measures toward different approaching threats. We considered that the distance at which targeted individuals noticed an approaching object (i.e., alert distance, AD) was related to vigilance, whereas FID represented risk assessment, which is related to habituation. We applied a predictive framework using AD and FID to Eurasian red squirrels’ responses to multiple threats of different risk levels (i.e., humans, model predators, and novel objects). AD was shorter in urban individuals compared with rural ones but not different among the approaching objects. FID was shorter in urban individuals and also varied among the objects with the shortest FID toward humans, whereas rural individuals showed similar FID to the different objects. These results suggest that, although urban individuals showed reduced vigilance, they could still assess different risk levels. Our framework can easily be applied to many animals and could significantly improve our understanding of wild animals’ adaptations to urban environments.
The historical distribution of megaherbivores does not determine the distribution of megafaunal fruit in southern Africa
Authors: Bunney Katherine , Robertson Mark , Bond William
Published: June 2019

Large specialized fruit (megafaunal fruit) have evolved alongside megaherbivores to take advantage of their unparalleled seed dispersal service. Megaherbivores were widespread and abundant in the Pleistocene but due to multiple extinction events have been extirpated from all continents except Africa and small pockets of South East Asia. In Africa, we are in the unique position of being able to study megafaunal fruits where there are still areas with a largely intact megaherbivore community. The megafaunal fruits of the African forests have been examined but those of the African savannas have been largely overlooked. We use an operational definition of megafaunal fruit developed in the Neotropics to identify megafaunal fruit in the South African tree flora. Thirty-one species were identified as megafaunal fruit-bearers, representing only 3% of the tree flora. Megafaunal tree species are well represented in the families Mimosoideae, Arecaceae, Strychnaceae and Caesalpinoideae. We explored the factors underlying the distribution of these megafaunal tree species. We found that the historical distribution of megaherbivores in South Africa does not explain the distribution of these fruit. Megaherbivores have historically been found throughout South Africa while megafaunal fruit tree species occur almost exclusively in the northern tropical reaches of the country. Abiotic factors such as precipitation and temperature appear to best explain the distribution of megafaunal fruit species in the region. We conclude that megafaunal fruit are a tropical phenomenon and their tropical origins now limit their distribution.
Nonsense mutations in alpha-II spectrin in three families with juvenile onset hereditary motor neuropathy
Authors: Beijer Danique , Deconinck Tine , De Bleecker Jan L , Dotti Maria Teresa , Malandrini Alessandro , Urtizberea J Andoni , Zulaica Miren , López de Munain Adolfo , Asselbergh Bob , De Jonghe Peter , Baets Jonathan
Published: June 2019

Distal hereditary motor neuropathies are a rare subgroup of inherited peripheral neuropathies hallmarked by a length-dependent axonal degeneration of lower motor neurons without significant involvement of sensory neurons. We identified patients with heterozygous nonsense mutations in the αII-spectrin gene, SPTAN1, in three separate dominant hereditary motor neuropathy families via next-generation sequencing. Variable penetrance was noted for these mutations in two of three families, and phenotype severity differs greatly between patients. The mutant mRNA containing nonsense mutations is broken down by nonsense-mediated decay and leads to reduced protein levels in patient cells. Previously, dominant-negative αII-spectrin gene mutations were described as causal in a spectrum of epilepsy phenotypes.
Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment
Authors: McDew-White Marina , Li Xue , Nkhoma Standwell C , Nair Shalini , Cheeseman Ian , Anderson Tim J C
Published: June 2019

Malaria parasites have small extremely AT-rich genomes: microsatellite repeats (1–9 bp) comprise 11% of the genome and genetic variation in natural populations is dominated by repeat changes in microsatellites rather than point mutations. This experiment was designed to quantify microsatellite mutation patterns in Plasmodium falciparum. We established 31 parasite cultures derived from a single parasite cell and maintained these for 114–267 days with frequent reductions to a single cell, so parasites accumulated mutations during ∼13,207 cell divisions. We Illumina sequenced the genomes of both progenitor and end-point mutation accumulation (MA) parasite lines in duplicate to validate stringent calling parameters. Microsatellite calls were 99.89% (GATK), 99.99% (freeBayes), and 99.96% (HipSTR) concordant in duplicate sequence runs from independent sequence libraries, whereas introduction of microsatellite mutations into the reference genome revealed a low false negative calling rate (0.68%). We observed 98 microsatellite mutations. We highlight several conclusions: microsatellite mutation rates (3.12 × 10−7 to 2.16 × 10−8/cell division) are associated with both repeat number and repeat motif like other organisms studied. However, 41% of changes resulted from loss or gain of more than one repeat: this was particularly true for long repeat arrays. Unlike other eukaryotes, we found no insertions or deletions that were not associated with repeats or homology regions. Overall, microsatellite mutation rates are among the lowest recorded and comparable to those in another AT-rich protozoan (Dictyostelium). However, a single infection (>1011 parasites) will still contain over 2.16 × 103 to 3.12 × 104 independent mutations at any single microsatellite locus.
The Genome Sequence of the Anthelmintic-Susceptible New Zealand Haemonchus contortus
Authors: Palevich Nikola , Maclean Paul H , Baten Abdul , Scott Richard W , Leathwick David M
Published: June 2019

Internal parasitic nematodes are a global animal health issue causing drastic losses in livestock. Here, we report a H. contortus representative draft genome to serve as a genetic resource to the scientific community and support future experimental research of molecular mechanisms in related parasites. A de novo hybrid assembly was generated from PCR-free whole genome sequence data, resulting in a chromosome-level assembly that is 465 Mb in size encoding 22,341 genes. The genome sequence presented here is consistent with the genome architecture of the existing Haemonchus species and is a valuable resource for future studies regarding population genetic structures of parasitic nematodes. Additionally, comparative pan-genomics with other species of economically important parasitic nematodes have revealed highly open genomes and strong collinearities within the phylum Nematoda.
Introducing the RZ model for definition and optimization of the boundary of low emission zones
Authors: Kabiri Shahab , Hajihosseinlou Mansour , Kabiri Shabnam
Published: June 2019

Poor urban air quality is one of the most pressing environmental problems, and the rapid growth in the number of motor vehicles is a major contributor to it. To tackle this problem, low emission zones (LEZs) were introduced and they have been applied in many of the mega cities around the world. Yet, a scientific approach to design the boundaries of LEZs is missing. This study develops an innovative model to address this gap, using total vehicle kilometers traveled (VKT) as the basis. The model allows defining and/or optimizing the LEZ boundaries. It is applied for the Tehran metropolitan area, as a case study, and the results show the optimality of the existing LEZ boundaries; however, they challenge the efficiency of the proposed policies on modifying current boundaries.
Time to Rehospitalization in Patients With Schizophrenia Receiving Long-Acting Injectable Antipsychotics or Oral Antipsychotics
Authors: Lin Ching-Hua , Chen Feng-Chua , chan Hung-Yu , Hsu Chun-Chi
Published: June 2019

Background

This study aimed to investigate and compare time to rehospitalization in patients with schizophrenia receiving long-acting injectable antipsychotics (LAIs) after discharge with those receiving oral antipsychotics. Additionally, the trend of LAIs prescription rates was investigated.

Methods

Patients with schizophrenia (n = 13 087), who were discharged from the study hospital from 2006 to 2017, were followed-up under naturalistic conditions in the year after discharge. The primary outcome was time to rehospitalization. Survival analysis was used in the comparisons between LAIs and oral antipsychotics and between FGA-LAIs and SGA-LAIs. Simple linear regression and Cochrane-Armitage trend test were used to test whether a time trend existed for LAIs prescription rates.

Results

In the 1 year following discharge, patients in the LAIs group had a significantly lower rehospitalization rate and a significantly lengthened time to rehospitalization than those in the oral antipsychotics group. Rehospitalization rate and time to rehospitalization were not significantly different in patients receiving FGA-LAIs or SGA-LAIs. A significantly higher percentage of patients treated with FGA-LAIs received anticholinergic agents than those treated with SGA-LAIs. The LAIs prescription rate grew significantly from 2006 to 2017 by an average of 0.5% per year.

Conclusions

LAIs were significantly superior to oral antipsychotics in reducing rehospitalization risk, whereas SGA-LAIs were comparable with FGA-LAIs in reducing rehospitalization risk. However, use of concomitant anticholinergic agents was less frequent in the SGA-LAIs group than in the FGA-LAIs group. Increase in LAIs prescription rate may be due to growing experiences and success among clinicians in treating patients with LAIs.
Psychopharmacological Treatment of Schizophrenia Over Time in 30 908 Inpatients: Data From the AMSP Study
Authors: Toto Sermin , Grohmann Renate , Bleich Stefan , Frieling Helge , Maier Hannah B , Greil Waldemar , Cordes Joachim , Schmidt-Kraepelin Christian , Kasper Siegfried , Stübner Susanne , Degner Detlef , Druschky Katrin , Zindler Tristan , Neyazi Alexandra
Published: June 2019

Background

Psychotropic drugs are the cornerstone of schizophrenia treatment, often requiring lifelong treatment. Data on pharmacotherapy in inpatient settings are lacking.

Methods

Prescription data of schizophrenic inpatients within the time period 2000–2015 were obtained from the database of the Drug Safety Program in Psychiatry (AMSP). Data were collected at 2 index dates per year; the prescription patterns and changes over time were analyzed.

Results

Among 30 908 inpatients (mean age 41.6 years, 57.8% males), the drug classes administered most often were antipsychotics (94.8%), tranquilizers (32%), antidepressants (16.5%), antiparkinsonians (16%), anticonvulsants (14.1%), hypnotics (8.1%), and lithium (2.1%).

The use of second-generation antipsychotics significantly increased from 62.8% in 2000 to 88.9% in 2015 (P < .001), whereas the prescription of first-generation antipsychotics decreased from 46.6% in 2000 to 24.7% in 2015 (P < .001). The administration of long-acting injectable antipsychotics decreased from 15.2% in 2000 to 11.7% in 2015 (P = .006). Clopazine was the most often used antipsychotic, having been used for 21.3% of all patients. Polypharmacy rates (≥5 drugs) increased from 19% in 2000 to 26.5% in 2015. Psychiatric polypharmacy (≥3 psychotropic drugs) was present in 44.7% of patients.

Conclusions

Combinations of antipsychotics and augmentation therapies with other drug classes are frequently prescribed for schizophrenic patients. Though treatment resistance and unsatisfactory functional outcomes reflect clinical necessity, further prospective studies are needed on real-world prescription patterns in schizophrenia to evaluate the efficacy and safety of this common practice.
Repeated determination of moxifloxacin concentrations in interstitial space fluid of muscle and subcutis in septic patients
Authors: Nowak Hartmuth , Weidemann Caroline , Martini Stefan , Oesterreicher Zoe Anne , Dorn Christoph , Adamzik Michael , Kees Frieder , Zeitlinger Markus , Rahmel Tim
Published: June 2019

Background

For an effective antimicrobial treatment, it is crucial that antibiotics reach sufficient concentrations in plasma and tissue. Currently no data exist regarding moxifloxacin plasma concentrations and exposure levels in tissue under septic conditions.

Objectives

To determine the pharmacokinetics of moxifloxacin in plasma and interstitial space fluid over a prolonged period.

Patients and methods

Ten septic patients were treated with 400 mg of moxifloxacin once a day; on days 1, 3 and 5 of treatment plasma sampling and microdialysis in the subcutis and muscle of the upper thigh were performed to determine concentrations of moxifloxacin in different compartments. This trial was registered in the German Clinical Trials Register (DRKS, register number DRKS00012985).

Results

Mean unbound fraction of moxifloxacin in plasma was 85.5±3.4%. On day 1, Cmax in subcutis and muscle was 2.8±1.8 and 2.5±1.3 mg/L, respectively, AUC was 24.8±15.1 and 21.3±10.5 mg·h/L, respectively, and fAUC0–24/MIC was 100.9±62.9 and 86.5±38.3 h, respectively. Cmax for unbound moxifloxacin in plasma was 3.5±0.9 mg/L, AUC was 23.5±7.5 mg·h/L and fAUC0–24/MIC was 91.6±24.8 h. Key pharmacokinetic parameters on days 3 and 5 showed no significant differences. Clearance was higher than in healthy adults, but tissue concentrations were comparable, most likely due to a lower protein binding.

Conclusions

Surprisingly, the first dose already achieved exposure comparable to steady-state conditions. The approved daily dose of 400 mg was adequate in our patient population. Thus, it seems that in septic patients a loading dose on the first day of treatment with moxifloxacin is not required.
Productivity of Neoseiulus bicaudus (Acari: Phytoseiidae) Reared on Natural Prey, Alternative Prey, and Artificial Diet
Authors: Su Jie , Dong Fang , Liu Si-min , Lu Yan-hui , Zhang Jian-ping
Published: June 2019

The predatory mite, Neoseiulus bicaudus (Wainstein), is a potential biological control agent against spider mites and thrips. The objective of this experiment was to compare the effects of three diets on the life table of N. bicaudus. The three diets were 1) Tetranychus turkestani (Ugarov & Nikolskii) (Acari: Tetranychidae), the natural prey of N. bicaudus; 2) Tyrophagus putrescentiae (Schrank) (Acari: Acaridae), an alternative prey; and 3) artificial diet primarily consisting of decapsulated shrimp cysts, egg yolk, and honey. The computer simulation was used to project the population growth of N. bicaudus fed on different diets. The preadult developmental time (3.83 d) of N. bicaudus was shortest, and the intrinsic rate of increase (r = 0.2782 d−1) and the net reproductive rate (R0 = 18.98 offspring) were highest when reared on the alternative prey Ty. putrescentiae. The total development time (7.37 d) was longest, and the population parameters were the lowest (r = −0.0081 d−1, R0 = 0.85 offspring) when N. bicaudus was reared on artificial diet. The population projection showed that the population of N. bicaudus reared on Ty. putrescentiae could increase fast. Our results showed that the Ty. putrescentiae was the most suitable prey for mass rearing of N. bicaudus. The artificial diet could not support the N. bicaudus population and needs to be improved.
Can a microdynamic approach to sleep-onset imagery solve the overabundance problem of dreaming? Commentary on Tore Nielsen’s “Microdream neurophenomenology”
Authors: Windt Jennifer M
Published: June 2019

Nielsen proposes that a microdynamic approach to experiences occurring in the earliest stages of sleep onset, which he calls microdreams, can shed light on the process of dream imagery formation. I discuss microdreams in the context of simulation views, in which dreaming is defined as the immersive experience of a virtual world centered on a virtual self. I also evaluate his proposal to expand the dimensions included in the oneiragogic spectrum by kinesis. I conclude that while a subset of microdreams might not fulfill the conditions to count as even minimal dreams, their investigation can nonetheless help address key questions in dream research and may even constitute a distinctive pathway to the generation of full-fledged dreaming.
Tort Liability for Belligerent Wrongs
Authors: Abraham Haim
Published: June 2019

Most legal systems deny civilians a right to compensation for losses they sustain during belligerent activities. Arguments for recognising such a right are usually divorced, to various degrees, from the moral and legal underpinnings of the notion of inflicting a wrongful loss under either international humanitarian law or domestic tort law. My aim in this article is to advance a novel account of states’ tortious liability for belligerent wrongdoing, drawing on both international humanitarian law and corrective justice approaches to domestic tort law. Structuring my account on both frameworks, I argue that some of the losses that states inflict during war are private law wrongs that establish a claim of compensation in tort. Only in cases where the in bello principles are observed can losses to person and property be justified and non-wrongful. Otherwise, they constitute wrongs, which those who inflict them have duties of corrective justice to repair.
Knockdown of Arabidopsis ROOT UVB SENSITIVE4 Disrupts Anther Dehiscence by Suppressing Secondary Thickening in the Endothecium
Authors: Zhao Shu-Qing , Li Wen-Chao , Zhang Yi , Tidy Alison C , Wilson Zoe A
Published: June 2019

ROOT UV-B SENSITIVE4 (RUS4) encodes a protein with no known function that contains a conserved Domain of Unknown Function 647 (DUF647). The DUF647-containing proteins RUS1 and RUS2 have previously been associated with root UV-B-sensing pathway that plays a major role in Arabidopsis early seedling morphogenesis and development. Here, we show that RUS4 knockdown Arabidopsis plants, referred to as amiR-RUS4, were severely reduced in male fertility with indehiscent anthers. Light microscopy of anther sections revealed a significantly reduced secondary wall thickening in the endothecium of amiR-RUS4 anthers. We further show that the transcript abundance of the NAC domain genes NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1) and NST2, which have been shown to regulate the secondary cell wall thickenings in the anther endothecium, were dramatically reduced in the amiR-RUS4 floral buds. Expression of the secondary cell wall-associated MYB transcription factor genes MYB103 and MYB85 were also strongly reduced in floral buds of the amiR-RUS4 plants. Overexpression of RUS4 led to increased secondary thickening in the endothecium. However, the rus4-2 mutant exhibited no obvious phenotype. Promoter-GUS analysis revealed that the RUS4 promoter was highly active in the anthers, supporting its role in anther development. Taken together, these results suggest that RUS4, probably functions redundantly with other genes, may play an important role in the secondary thickening formation in the anther endothecium by indirectly affecting the expression of secondary cell wall biosynthetic genes.
Representative Group Styles: How Ally Immigrant Rights Organizations Promote Immigrant Involvement
Authors: Yukich Grace , Fulton Brad R , Wood Richard L
Published: June 2019

Why are some organizations more successful than others at involving socially diverse groups of people? Previous research emphasizes the role representative leaders play in recruiting diverse constituencies. This study extends that research by analyzing how an organization’s group style—its customs that shape everyday interactions—influences constituent involvement by either bridging or reinforcing social divides. Our multi-method approach examines ally immigrant rights organizations to assess the relationship between their group styles and their ability to involve immigrants. Ethnographic data reveal that divergent levels of immigrant involvement in two organizations can be explained by differences in the organizations’ group styles—specifically, differences in their religious, class-based, and linguistic practices. Original survey data from a national sample of ally organizations demonstrate the generalizability of our findings. Our analysis shows how having an immigrant-friendly group style can promote immigrant involvement, indicating that an organization’s style is associated with its social composition. Having representative leaders from immigrant groups, though positively associated with immigrant involvement, is insufficient for sustaining immigrant involvement; group style can moderate the effect of having representative leaders. This research suggests that organizations seeking to recruit and retain a diverse social base could benefit from cultivating a representative group style.
Indirect Sexual Selection Drives Rapid Sperm Protein Evolution
Authors: Wilburn Damien B. , Tuttle Lisa M. , Klevit Rachel E. , Swanson Willie J.
Published: June 2019

Sexual selection can explain rapid evolution of fertilization proteins, yet sperm proteins evolve rapidly even if they are not directly involved in fertilization. Here we demonstrate that FITZAP, an intrinsically disordered sperm protein in the marine mollusk abalone, exploits differences in the intracellular and oceanic ionic environments to package the fertilization protein lysin at extraordinary concentrations inside sperm by forming Fuzzy Interacting Transient Zwitterion (FITZ) complexes. FITZAP binds lysin at the same protein interface as its egg receptor VERL, and as sexual selection rapidly alters the lysin-VERL interface, FITZAP coevolves rapidly to maintain lysin binding. Consequently, FITZAP-lysin interactions exhibit a similar species-specificity as lysin-VERL interactions. Thus, tethered molecular arms races driven by sexual selection can generally explain rapid sperm protein evolution.

One Sentence Summary

Structural study of sperm proteins reveals a novel protein packaging/dispersion system embedded in a coevolutionary arms race.
NINscope: a versatile miniscope for multi-region circuit investigations
Authors: de Groot Andres , van den Boom Bastijn J.G. , van Genderen Romano M. , Coppens Joris , van Veldhuijzen John , Bos Joop , Hoedemaker Hugo , Negrello Mario , Willuhn Ingo , De Zeeuw Chris I. , Hoogland Tycho M.
Published: June 2019

Miniaturized fluorescence microscopes (miniscopes) have been instrumental to monitor neural activity during unrestrained behavior and their open-source versions have helped to distribute them at an affordable cost. Generally, the footprint and weight of open-source miniscopes is sacrificed for added functionality. Here, we present NINscope: a light-weight, small footprint, open-source miniscope that incorporates a high-sensitivity image sensor, an inertial measurement unit (IMU), and an LED driver for an external optogenetic probe. We highlight the advantages of NINscope by performing the first simultaneous cellular resolution (dual scope) recordings from cerebellum and cerebral cortex in unrestrained mice, revealing that the activity of both regions generally precedes the onset of behavioral acceleration. We further demonstrate the optogenetic stimulation capabilities of NINscope and show that cerebral cortical activity can be driven strongly by cerebellar stimulation. To validate the performance of our miniscope to image from deep-brain regions, we recorded in the dorsal striatum and, using the IMU to assess turning movements, replicate previous studies that show encoding of action space in this subcortical region. Finally, we combine optogenetic stimulation of distinct cortical regions projecting to the dorsal striatum, to probe functional connectivity. In combination with cross-platform control software, NINscope is a versatile addition to the expanding toolbox of open-source miniscopes and will aid multi-region circuit investigations during unrestrained behavior.
Noradrenergic but not dopaminergic neurons signal task state changes and predict re-engagement after a failure
Authors: Jahn Caroline I , Varazzani Chiara , Sallet Jérôme , Walton Mark E , Bouret Sébastien
Published: June 2019

The two catecholamines, noradrenaline and dopamine, have been shown to play comparable roles in behaviour. Both noradrenergic and dopaminergic neurons respond to salient cues predicting reward availability and to stimulus novelty, and shape action selection strategies. However, their roles in motivation have seldom been directly compared. We therefore examined the activity of noradrenergic neurons in the locus coeruleus and putative midbrain dopaminergic neurons in monkeys cued to perform effortful actions for rewards. The activity in both regions correlated with the likelihood of engaging with a presented option. By contrast, only noradrenaline neurons were also (i) predictive of engagement in a subsequent trial following a failure to engage and (ii) sensitive to the task state change, the discovery of the new task condition in unrepeated trials. This indicates that while dopamine is primarily important for the promotion of actions directed towards currently available rewards, noradrenergic neurons play a crucial complementary role in mobilizing resources to promote future engagement.
MERTK on mononuclear phagocytes regulates T cell antigen recognition at autoimmune and tumor sites
Authors: Lindsay Robin S. , Whitesell Jennifer C. , Dew Kristen E. , Rodriguez Erika , Sandor Adam M. , Tracy Dayna , Yannacone Seth F. , Basta Brittany N. , Jacobelli Jordan , Friedman Rachel S.
Published: June 2019

Understanding mechanisms of immune regulation is key to developing immunotherapies for autoimmunity and cancer. We examined the role of mononuclear phagocytes during peripheral T cell regulation in type 1 diabetes and melanoma. MERTK expression and activity in mononuclear phagocytes in the pancreatic islets, promoted islet T cell regulation, resulting in reduced sensitivity of T cell scanning for cognate antigen in pre-diabetic islets. MERTK-dependent regulation led to reduced T cell activation and effector function at the disease site in the islets and prevented rapid progression of type 1 diabetes. In human islets, MERTK-expressing cells were increased in remaining insulin-containing islets of type 1 diabetic patients, suggesting that MERTK protects the islets from autoimmune destruction. MERTK also regulated T cell arrest in melanoma tumors. These data indicate that MERTK signaling in mononuclear phagocytes drives T cell regulation at inflammatory disease sites in peripheral tissues through a mechanism that reduces the sensitivity of scanning for antigen leading to reduced responsiveness to antigen.
Reliable longitudinal brain age prediction in stroke patients: Associations with cognitive function and response to cognitive training
Authors: Richard Geneviève , Kolskår Knut , Ulrichsen Kristine M. , Kaufmann Tobias , Alnæs Dag , Sanders Anne-Marthe , Dørum Erlend S. , Sánchez Jennifer Monereo , Petersen Anders , Ihle-Hansen Hege , Nordvik Jan Egil , Westlye Lars T.
Published: June 2019

Cognitive deficits are important predictors for outcome, independence and quality of life after stroke, but often remain unnoticed and unattended because other impairments are more evident. Computerized cognitive training (CCT) is among the candidate interventions that may alleviate cognitive difficulties, but the evidence supporting its feasibility and effectiveness is scarce, partly due to the lack of tools for outcome prediction and monitoring. Magnetic resonance imaging (MRI) provides candidate markers for disease monitoring and outcome prediction. By integrating information not only about lesion extent and localization, but also regarding the integrity of the unaffected parts of the brain, advanced MRI provides relevant information for developing better prediction models in order to tailor cognitive intervention for patients, especially in a chronic phase.

Using brain age prediction based on MRI based brain morphometry and machine learning, we tested the hypotheses that stroke patients with a younger-appearing brain relative to their chronological age perform better on cognitive tests and benefit more from cognitive training compared to patients with an older-appearing brain. In this randomized double-blind study, 54 patients who suffered mild stroke (>6 months since hospital admission, NIHSS<7 at hospital discharge) underwent 3-weeks CCT and MRI before and after the intervention. In addition, patients were randomized to one of two groups receiving either active or sham transcranial direct current stimulation (tDCS). We tested for main effects of brain age gap (estimated age – chronological age) on cognitive performance, and associations between brain age gap and task improvement. Finally, we tested if longitudinal changes in brain age gap during the intervention were sensitive to treatment response. Briefly, our results suggest that longitudinal brain age prediction based on automated brain morphometry is feasible and reliable in stroke patients. However, no significant association between brain age and both performance and response to cognitive training were found.