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Insight into the neural basis of hedonic processing has come from studies of food palatability in rodents. Pharmacological manipulations of the nucleus accumbens shell (NAcSh) have repeatedly been demonstrated to increase hedonic taste reactivity, yet the contribution of specific NAcSh circuit components is unknown. Bidirectional optogenetic manipulations were targeted to the principal NAcSh projection neurons and afferent pathways in mice during free feeding assays. Number of licks per bout of consumption was used as a measure of food palatability as it was confirmed to track sucrose concentration and subjective flavor preferences. Photoinhibition of NAcSh neurons, whether general or cell-type specific, was found to alter consumption without affecting its hedonic impact. Among the principal excitatory afferent pathways, we showed that ventral hippocampal (vHipp) input alone enhances palatability upon low-frequency photostimulation time-locked to consumption. This enhancement in palatability was independent of opioid signaling and not recapitulated by NAcSh or dopamine neuron photostimulation. We further demonstrated that vHipp input photostimulation is sufficient to condition a flavor preference, while its inhibition impedes sucrose-driven flavor preference conditioning. These results demonstrate a novel contribution of vHipp–NAcSh pathway activity to palatability that may relate to its innervation of a particular region or neuronal ensemble in the NAcSh. These findings are consistent with the evidence that vHipp–NAcSh activity is relevant to the pathophysiology of anhedonia and depression as well as the increasing appreciation of hippocampal involvement in people's food pleasantness ratings, hunger, and weight. [ABSTRACT FROM AUTHOR]

Hand grip strength has been widely used as a lead measure in geriatric conditions such as frailty. However, diversity in assessment protocols and methodologies creates uncertainty in the comparison of outcome measurements. The aim of this study was to review the literature relating to the measurement of hand grip strength in older adults, in order to develop further consensus in relation to the use of existing protocols in clinical and community settings, with an emphasis on practicality and suitability for frail persons. Five electronic English databases were searched using keywords such as 'hand grip strength', 'clinimetric assessment', and their synonyms. Age-related trends in adults aged ≥65 years were assessed, and comparisons were made of the following variables: dynamometer model and handle setting, hand positioning, warm-up trials, grip duration, number of repeated tests, rest periods, laterality of tested hand, and whether encouragement was given to the subjects. Thirty-four research papers met the inclusion criteria and were included. A Jamar hand dynamometer was most frequently used. Variations were found in the positioning of the subject and in the duration of the rest period, which ranged from 10 to 20 s to 1 min. Grip strength was typically measured three times in the dominant hand, with the strongest grip being recorded and no encouragement being provided during assessment. Based on the scoping review, we propose a detailed and standardised protocol that is suitable for the assessment of hand grip strength in frail older adults. [ABSTRACT FROM AUTHOR]

Forced air cooling studies are hindered by the practical difficulties and cost associated with pallet scale investigations. Produce simulators are a potential solution for overcoming some of these difficulties. Despite their common use in precooling research, there are a lack of design guidelines for such simulators in the literature which in some case has led to their inappropriate use. This review examines previous use of produce simulators in produce cooling studies in the context of transport phenomena theory. This allows constraints to be proposed which facilitate the design of produce simulators that can replicate transport phenomena in horticultural produce. These include the requirements of geometric and thermal property matching as well as the practical constraints imposed on produce simulators. It is suggested that future computational modelling work is well suited to the establishment of produce simulator design guidelines which incorporate complex effects such as the impact of variation in produce geometry on flow. The material engineering challenges posed by produce simulators are also discussed. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences. Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs). We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures. Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non–type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P =.03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells. NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed. [ABSTRACT FROM AUTHOR]

Summary: Ginseng alone or combined with other herbs has been increasingly used for chronic obstructive pulmonary disease (COPD). This review aims to evaluate the effectiveness and safety of oral Ginseng formulae for stable COPD. Four English databases and three Chinese databases were searched to identify randomized controlled trials. Methodological quality was assessed by Cochrane risk of bias and Jadad’s scale. Data were analyzed using Review Manager 5.0. Twelve studies overall of low quality, involving 1560 participants were included. Results of three studies showed a mean difference (MD) of 0.30 (95%CI 0.02 to 0.58) for forced expiratory volume in 1 s (FEV1) improvement of Ginseng formulae versus placebo control. Findings of three studies revealed an MD of 9.43 (95%CI 3.64 to 15.21) of FEV1 % predicted between Ginseng formulae and placebo control. Quality of life (Qol) measured by St. George’s Respiratory Questionnaire was improved (MD −10.32, 95%CI −14.99 to −5.65) with Ginseng formulae plus pharmacotherapy versus pharmacotherapy alone in one study. There were no severe adverse events reported. Ginseng formulae for stable COPD patients show promising evidence of lung functions and Qol improvement. However, the degree of benefit is uncertain due to potential risk of bias of the included studies. [ABSTRACT FROM AUTHOR]

[Display omitted] • A hybrid quantitative method combining a PLS and a Soft Sensor potency estimation. • Implemented and applied on continuous direct compression manufacturing. • Improved overall estimation robustness and facilitates cross-site method transfer. Near Infrared (NIR) spectroscopy is commonly utilized for continuous manufacturing as Process Analytical Technology (PAT) tool. This paper focus on a continuous direct compression manufacturing process, in which an NIR PAT probe is integrated into the tablet press feed frame and into the tablet diversion control system to ensure continuous monitoring of the potency and homogeneity of the blend within the process line. The quantification of NIR spectra is achieved through Partial Least-Squares (PLS) modeling, calibrated with offline analyzed tablet cores at different potency levels. Because the NIR measurements are often sensitive to sample physical properties caused by raw materials or process conditions, etc., adopting a data-driven approach will require a large amount of representative data throughout the method lifecycle. During the early stages of process development, whenever new uncaptured source of variability in the model space are encountered, the chemometric predictions can deviate from the offline reference, requiring frequent model updates. These deviations can be reduced by integrating process and physico-chemical knowledge in the on-line potency estimation. This paper presents a novel hybrid method combining the online NIR PLS and a potency soft sensor estimation, enabling a robust potency prediction whilst minimizing maintenance downtimes and facilitating cross-site method transfer. [ABSTRACT FROM AUTHOR]

[Display omitted] • A material sparing quantitative NIR method was developed for saccharin blend potency. • The method was developed at lab and deployed in continuous mfg. scale at two sites. The method was accurate and robust against material, instrument and process variation. A Near Infrared (NIR) method was developed using a small benchtop feed frame system to quantify Saccharin potency in a powder blend during continuous manufacturing process. A 15-point Design of Experiments (DoE) was created based on the NIR spectral response and compositions of the formulation to develop a calibration set. The calibration set was designed to create compositional and raw material lots variation using minimum resources. The calibration experiments utilized around 0.5 kg Saccharin (Active Pharmaceutical Ingredient (API) surrogate) and 1.8 kg of excipients. Partial Least Square (PLS) modeling was used to develop a quantitative NIR method from the calibration data. The NIR method was implemented during 5 test batches in two different manufacturing sites across different potency levels at a continuous manufacturing platform for direction compression. Acceptable prediction performance was achieved from the NIR method at both sites. The NIR method was robust against changes in process scale and NIR instruments. The variance information built into the calibration set was found to be critical to successful model performance. This study shows a benchtop feed frame can be used for material sparing calibration method development without operating at a full-scale process line and applied across multiple sites, instruments at different potency levels. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel NIR method was developed for blend potency variation and deviation detection. • NIR method developed at a lab scale was directly applied to full-scale manufacturing. • The method was robust against raw material, instrument, and process variation. • It enables agile NIR development and enhanced performance in continuous manufacturing. Near Infrared (NIR) method for blend potency estimation has been commonly used as an essential tool for process monitoring and control in continuous manufacturing of solid oral dosage forms. Robustness has been the main challenge for successful application of an NIR method, which often results in a long development time with frequent method update. Robustness deficiency often presents as an offset (bias) on the mean potency estimation. In this paper, the purpose of the NIR method has been redefined from estimating potency to potency deviation. This quantitative approach uses the mean centered potency to estimate potency deviations from the process mean, therefore, detects the non-conforming materials for continuous process monitoring and control. An NIR method was developed at the lab benchtop scale and directly deployed to a direct compression continuous manufacturing platform at Pfizer for mean centered potency estimation. The benchtop calibration provided a speedy and efficient NIR method development and the method showed enhanced robustness for estimating potency deviation in presence of wide process and raw material variations. Integrating with the mean centered approach, the NIR model from the lab could be implemented to different sites using different instruments without requiring model update for the established range of process conditions and raw material properties. [ABSTRACT FROM AUTHOR]

Cue-evoked midbrain dopamine (DA) neuron activity reflects expected value, but its influence on reward assessment is unclear. In mice performing a trial-based operant task, we test if bidirectional manipulations of cue or operant-associated DA neuron activity drive learning as a result of under- or overexpectation of reward value. We target optogenetic manipulations to different components of forced trials, when only one lever is presented, and assess lever biases on choice trials in the absence of photomanipulation. Although lever biases are demonstrated to be flexible and sensitive to changes in expected value, augmentation of cue or operant-associated DA signaling does not significantly alter choice behavior, and blunting DA signaling during any component of the forced trials reduces choice trial responses on the associated lever. These data suggest cue-evoked DA helps maintain cue-value associations but does not encode expected value as to set the benchmark against which received reward is judged. • Operant choice behavior is driven by differences in expected value • Cue-evoked midbrain dopamine (DA) neuron activity reflects expected value • Disrupting cue-evoked DA interferes with the maintenance of cue-value associations • Manipulations of cue-evoked DA signaling do not lead to under- or overexpectation Although reward-predictive cues increase midbrain dopamine neuron activity in proportion to the expected value of the anticipated reward, Mendoza et al. demonstrate that cue-evoked dopamine does not prospectively encode expected value as to influence reward assessment. Rather, cue-evoked dopamine is important for the maintenance of cue-value associations. [ABSTRACT FROM AUTHOR]

Abstract: Dendrites and spines undergo dynamic changes in physiological and pathological conditions. Dendritic outgrowth has been observed in surviving neurons months after ischemia, which is associated with the functional compensation. It remains unclear how dendrites in surviving neurons are altered shortly after ischemia, which might reveal the mechanisms underlying neuronal survival. Using primary cortical cultures, we monitored the dendritic changes in individual neurons after oxygen-glucose deprivation (OGD). Two to four hours of OGD induced approximately 30–50% cell death in 24h. However, the total dendritic length in surviving neurons was significantly increased after OGD with a peak at 6h after re-oxygenation. The increase of dendritic length after OGD was mainly due to the sprouting rather than the extension of the dendrites. The dendritic outgrowth after 2h of OGD was greater than that after 4h of OGD. Application of NMDA receptor blocker MK-801 abolished OGD-induced dendritic outgrowth, whereas application of AMPA receptor antagonist CNQX had no significant effects. These results demonstrate a NMDA receptor-dependent dendritic plasticity shortly after OGD, which provides insights into the early response of surviving neurons after ischemia. [Copyright &y& Elsevier]

Summary The childhood-onset motor disorder DYT6 dystonia is caused by loss-of-function mutations in the transcription factor THAP1, but the neurodevelopmental processes in which THAP1 participates are unknown. We find that THAP1 is essential for the timing of myelination initiation during CNS maturation. Conditional deletion of THAP1 in the CNS retards maturation of the oligodendrocyte (OL) lineage, delaying myelination and causing persistent motor deficits. The CNS myelination defect results from a cell-autonomous requirement for THAP1 in the OL lineage and is recapitulated in developmental assays performed on OL progenitor cells purified from Thap1 null mice. Loss of THAP1 function disrupts a core set of OL maturation genes and reduces the DNA occupancy of YY1, a transcription factor required for OL maturation. These studies establish a role for THAP1 transcriptional regulation at the inception of myelination and implicate abnormal timing of myelination in the pathogenesis of childhood-onset dystonia. [ABSTRACT FROM AUTHOR]