Methamphetamine (METH) abuse among women has recently increased to levels comparable to those observed in men. Although studies using animal models of addiction have begun to include more female ...subjects, examination of the effects of drugs of abuse on post-partum females is currently lacking. This is especially important in light of the significant hormonal and neurobiological changes that accompany pregnancy and rearing experiences. Furthermore, stress in a known factor in addiction vulnerability and the post-partum experience in the clinical population can be highly stressful. Here, we utilized the conditioned place preference paradigm to investigate the conditioned rewarding effects of METH either in virgin rats or in dams exposed to brief separation (15 min) or long separation (180 min) from the litter. We found that females in the brief separation group showed significantly greater METH conditioned place preference compared with both the long separation and virgin groups. No differences were found in locomotor activity during the conditioning sessions. These findings suggest that peripartum experience and brief litter separation may enhance the rewarding effects of METH.
Consider the multiple linear regression model
Y
=
β
1
+
β
2
x
2
+
⋯
+
β
p
x
p
+
e
=
x
T
β
+
e
with sample size
n
. This paper compares the six shrinkage estimators: forward selection, lasso, partial ...least squares, principal components regression, lasso variable selection, and ridge regression, with large sample theory and two new prediction intervals that are asymptotically optimal if the estimator
β
^
is a consistent estimator of
β
. Few prediction intervals have been developed for
p
>
n
, and they are not asymptotically optimal. For
p
fixed, the large sample theory for variable selection estimators like forward selection is new, and the theory shows that lasso variable selection is
n
consistent under much milder conditions than lasso. This paper also simplifies the proofs of the large sample theory for lasso, ridge regression, and elastic net.
Summary
Deinococcus spp are among the most radiation‐resistant micro‐organisms that have been discovered. They show remarkable resistance to a range of damage caused by ionizing radiation, ...desiccation, UV radiation and oxidizing agents. Traditionally, Escherichia coli and Saccharomyces cerevisiae have been the two platforms of choice for engineering micro‐organisms for biotechnological applications, because they are well understood and easy to work with. However, in recent years, researchers have begun using Deinococcus spp in biotechnologies and bioremediation due to their specific ability to grow and express novel engineered functions. More recently, the sequencing of several Deinococcus spp and comparative genomic analysis have provided new insight into the potential of this genus. Features such as the accumulation of genes encoding cell cleaning systems that eliminate organic and inorganic cell toxic components are widespread among Deinococcus spp. Other features such as the ability to degrade and metabolize sugars and polymeric sugars make Deinococcus spp. an attractive alternative for use in industrial biotechnology.
Experiences of trauma in childhood and adulthood are highly prevalent among service users accessing acute, crisis, emergency, and residential mental health services. These settings, and restraint and ...seclusion practices used, can be extremely traumatic, leading to a growing awareness for the need for trauma informed care (TIC). The aim of TIC is to acknowledge the prevalence and impact of trauma and create a safe environment to prevent re-traumatisation. This scoping review maps the TIC approaches delivered in these settings and reports related service user and staff experiences and attitudes, staff wellbeing, and service use outcomes.We searched seven databases (EMBASE; PsycINFO; MEDLINE; Web of Science; Social Policy and Practice; Maternity and Infant Care Database; Cochrane Library Trials Register) between 24/02/2022-10/03/2022, used backwards and forwards citation tracking, and consulted academic and lived experience experts, identifying 4244 potentially relevant studies. Thirty-one studies were included.Most studies (n = 23) were conducted in the USA and were based in acute mental health services (n = 16). We identified few trials, limiting inferences that can be drawn from the findings. The Six Core Strategies (n = 7) and the Sanctuary Model (n = 6) were the most commonly reported approaches. Rates of restraint and seclusion reportedly decreased. Some service users reported feeling trusted and cared for, while staff reported feeling empathy for service users and having a greater understanding of trauma. Staff reported needing training to deliver TIC effectively.TIC principles should be at the core of all mental health service delivery. Implementing TIC approaches may integrate best practice into mental health care, although significant time and financial resources are required to implement organisational change at scale. Most evidence is preliminary in nature, and confined to acute and residential services, with little evidence on community crisis or emergency services. Clinical and research developments should prioritise lived experience expertise in addressing these gaps.
We generated human iPS derived neural stem cells and differentiated cells from healthy control individuals and an individual with autism spectrum disorder carrying bi-allelic NRXN1-alpha deletion. We ...investigated the expression of NRXN1-alpha during neural induction and neural differentiation and observed a pivotal role for NRXN1-alpha during early neural induction and neuronal differentiation. Single cell RNA-seq pinpointed neural stem cells carrying NRXN1-alpha deletion shifting towards radial glia-like cell identity and revealed higher proportion of differentiated astroglia. Furthermore, neuronal cells carrying NRXN1-alpha deletion were identified as immature by single cell RNA-seq analysis, displayed significant depression in calcium signaling activity and presented impaired maturation action potential profile in neurons investigated with electrophysiology. Our observations propose NRXN1-alpha plays an important role for the efficient establishment of neural stem cells, in neuronal differentiation and in maturation of functional excitatory neuronal cells.
Display omitted
•Disease modeling of autism in iPS derived neural stem cells carrying bi-allelic NRXN1-alpha deletion.•Single cell analysis accurately resolves genes and cell identities.•Deletion of NRXN1-alpha skews neural stem cells towards radial glia-like cells with preference for generating astroglia.•Deletion of NRXN1-alpha depresses calcium-signaling activity and impairs maturation in excitatory neurons.
Local field potential (LFP) deflections and oscillations define hippocampal sharp-wave ripples (SWRs), one of the most synchronous events of the brain. SWRs reflect firing and synaptic current ...sequences emerging from cognitively relevant neuronal ensembles. While spectral analysis have permitted advances, the surge of ultra-dense recordings now call for new automatic detection strategies. Here, we show how one-dimensional convolutional networks operating over high-density LFP hippocampal recordings allowed for automatic identification of SWR from the rodent hippocampus. When applied without retraining to new datasets and ultra-dense hippocampus-wide recordings, we discovered physiologically relevant processes associated to the emergence of SWR, prompting for novel classification criteria. To gain interpretability, we developed a method to interrogate the operation of the artificial network. We found it relied in feature-based specialization, which permit identification of spatially segregated oscillations and deflections, as well as synchronous population firing typical of replay. Thus, using deep learning-based approaches may change the current heuristic for a better mechanistic interpretation of these relevant neurophysiological events.
Artificial intelligence is finding greater use in society through its ability to process data in new ways. One particularly useful approach known as convolutional neural networks is typically used for image analysis, such as face recognition. This type of artificial intelligence could help neuroscientists analyze data produced by new technologies that record brain activity with higher resolution.
Advanced processing could potentially identify events in the brain in real-time. For example, signals called sharp-wave ripples are produced by the hippocampus, a brain region involved in forming memories. Detecting and interacting with these events as they are happening would permit a better understanding of how memory works. However, these signals can vary in form, so it is necessary to detect several distinguishing features to recognize them.
To achieve this, Navas-Olive, Amaducci et al. trained convolutional neural networks using signals from electrodes placed in a region of the mouse hippocampus that had already been analyzed, and ‘telling’ the neural networks whether they got their identifications right or wrong. Once the networks learned to identify sharp-wave ripples from this data, they could then apply this knowledge to analyze other recordings. These included datasets from another part of the mouse hippocampus, the rat brain, and ultra-dense probes that simultaneously assess different brain regions. The convolutional networks were able to recognize sharp-wave ripple events across these diverse circumstances by identifying unique characteristics in the shapes of the waves.
These results will benefit neuroscientists by providing new tools to explore brain signals. For instance, this could allow them to analyze the activity of the hippocampus in real-time and potentially discover new aspects of the processes behind forming memories.
Tomato plants showing symptoms of yellow mottle and leaf distortion, first observed in eastern Cuba in 2007, have been shown to be associated with the presence of a novel bipartite begomovirus (genus
...Begomovirus
, family
Geminiviridae
) species, Tomato yellow leaf distortion virus (ToYLDV), for which the DNA-A has already been sequenced. Here, we present the completion of ToYLDV genome characterization by cloning and sequencing the DNA-B component. In addition, we constructed infectious clones that were used to inoculate tomato, soybean,
Nicotiana tabacum
and
N. benthamiana
plants by a biolistic procedure. Cloned ToYLDV reproduced the symptoms observed in tomato in the field, thus confirming that this begomovirus is the causal agent of the disease present in Cuba.
Purpose
Health-related quality of life (HRQOL) and pain are important supportive cancer care outcomes. The patient-provider relationship, a modifiable care experience, has been linked to healthcare ...outcomes; however, less is known about associations between patient-provider relationship and supportive care outcomes in cancer patients. We examined the role of multiple aspects of the patient-provider relationship in explaining patterns of HRQOL and pain among breast and lung cancer patients.
Methods
Our analysis included 283 breast and lung cancer patients from two cancer centers. Clinical data and survey data on patient sociodemographic factors, physical and mental HRQOL, pain, and patient-physician relationship (i.e., doctor’s respectfulness, time spent with doctors, patient involvement in decision-making, satisfaction with care, and following doctor’s advice/treatment plan) were collected at baseline and during treatment. We estimated adjusted modified Poisson regression models to assess associations between patient-physician relationship factors and physical and mental HRQOL and pain.
Results
Compared with patients reporting suboptimal respect from doctors, patients reporting optimal respect were less likely to report below average physical HRQOL (adjusted risk ratio (ARR), 0.73; 95%CI, 0.62–0.86), below average mental HRQOL (ARR, 0.71; 95%CI, 0.54–0.93), and moderate-to-severe pain (ARR, 0.53; 95%CI, 0.35–0.79). Patients reporting optimal involvement in care decision-making and patients who reported following their doctor’s advice/treatment plan were less likely to report below average mental HRQOL than their respective counterparts (ARR, 0.64; 95%CI, 0.50–0.83; ARR, 0.65; 95%CI, 0.48–0.86).
Conclusion
Multiple patient-physician relationship factors account for variations in HRQOL and pain in cancer patients. These findings provide insight into potential targets for improving the patient-provider relationship and supportive cancer care outcomes.
Pancreatic ductal adenocarcinoma (PDA) is a common, deadly cancer that is challenging both to diagnose and to manage. Its hallmark is an expansive, desmoplastic stroma characterized by high ...mechanical stiffness. In this study, we sought to leverage this feature of PDA for two purposes: differential diagnosis and monitoring of response to treatment.
Harmonic motion imaging (HMI) is a functional ultrasound technique that yields a quantitative relative measurement of stiffness suitable for comparisons between individuals and over time. We used HMI to quantify pancreatic stiffness in mouse models of pancreatitis and PDA as well as in a series of freshly resected human pancreatic cancer specimens.
In mice, we learned that stiffness increased during progression from preneoplasia to adenocarcinoma and also effectively distinguished PDA from several forms of pancreatitis. In human specimens, the distinction of tumors versus adjacent pancreatitis or normal pancreas tissue was even more stark. Moreover, in both mice and humans, stiffness increased in proportion to tumor size, indicating that tuning of mechanical stiffness is an ongoing process during tumor progression. Finally, using a brca2-mutant mouse model of PDA that is sensitive to cisplatin, we found that tissue stiffness decreases when tumors respond successfully to chemotherapy. Consistent with this observation, we found that tumor tissues from patients who had undergone neoadjuvant therapy were less stiff than those of untreated patients.
These findings support further development of HMI for clinical applications in disease staging and treatment response assessment in PDA.
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