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This study aimed to evaluate the effect of acupoint stimulation on pain, negative moods, and quality of life for head and neck cancer (HNC) patients who underwent concurrent chemoradiotherapy (CCRT).This randomized controlled trial recruited participants from a medical center and randomly assigned using a permuted block randomization list with computer-generated random serial numbers into the AcuCare groupAfter adjusting varying mucositis grades and time-dependent growth effects, the generalized estimating equations showed a significantly increase in pain intensity at weeks 1, 2, 3, and 6 (This study supports that acupoint stimulation could effectively reduce pain and improve senses problem of QoL for patients with HNC.This study was registered at https://clinicaltrials.gov/NCT03640195.

Porpose The aims of this study were to identify (1) the incidence and risk factors for axillary web syndrome (AWS) 4 weeks after axillary lymph node dissection (ALND) for individuals with breast cancer (BC), and (2) whether early-intervention physical therapy (PT) could reduce the recurrence of AWS.Methods A retrospective review of patients with BC receiving ALND and patients with AWS referred to receive PT twice weekly between January 2019 and December 2020 was performed.Results A total 173 breast cancer patients receiving ALND were enrolled. The incidence of AWS was 18%, and the time to diagnosis was 26.3 days. There was a predominant difference in age (p=0.004), number of removed lymph nodes (p = 0.044), and whether they were receiving neoadjuvant chemotherapy (p =0.002) between patients with and without AWS. These 3 factors were associated with an increased risk of developing AWS. Initial shoulder flexion and abduction were 132.1˚ and 123.4˚, respectively. After 14.8 PT sessions, shoulder flexion and abduction improved to 172.3˚ and 171.8˚, respectively. Improvement in shoulder ROM was 40.2˚ and 48.4˚ in flexion and abduction, respectively, which was significant (p < 0.001).Conclusion Younger age, higher number of removed lymph nodes and receiving neoadjuvant chemotherapy were associated with an increased risk of developing AWS. Early intervention with a PT program could effectively restore shoulder function and decrease the incidence of AWS in long-term follow-up.

Variations in neuronal connectivity occur widely in nervous systems from invertebrates to mammals. Yet, it is unclear how neuronal variability originates, to what extent and at what time scales it exists, and what functional consequences it might carry. To assess inter- and intraindividual neuronal variability, it would be ideal to analyze the same identified neuron across different brain hemispheres and individuals. Here, using genetic labeling and electron microscopy connectomics, we show that an identified inhibitory olfactory local interneuron, TC-LN, exhibits extraordinary variability in its glomerular innervation patterns. Moreover, TC-LN’s innervation of the VL2a glomerulus, which processes food signals and modulates mating behavior, is sexually dimorphic, is influenced by female’s courtship experience, and correlates with food intake in mated females. Mating also affects output connectivity of TC-LN to specific local interneurons. We propose that mating-associated variability of TC-LNs regulates how food odor is interpreted by an inhibitory network to modulate feeding.

Summary Walking trajectory is frequently measured to assess animal behavior. Air-supported spherical treadmills have been developed for real-time monitoring of animal walking trajectories. However, current systems for mice mainly employ computer mouse microcameras (chip-on-board sensors) to monitor ball motion, and these detectors exhibit technical issues with focus and rotation scale. In addition, computational methods to analyze and quantify the “random walk” of organisms are under-developed. In this work, we overcame the hurdle of frame-to-signal translation to develop a treadmill system with camera-based detection. Moreover, we generated a package of mathematical methods to quantify distinct aspects of Drosophila walking trajectories. By extracting and quantifying certain features of walking dynamics with high temporal resolution, we found that depending on their internal state, flies employ different walking strategies to approach environmental cues. This camera-based treadmill system and method package may also be applicable to monitor the walking trajectories of other diverse animal species., Graphical Abstract, Highlights • A camera-mode treadmill system was built to track Drosophila walking trajectories • Four key features were identified to describe walking strategies • Ball rotation is indispensable for full characterization of trajectories • Fed and starved control flies show no obvious differences in their random walk, Biological Sciences; Evolutionary Biology; Biophysics; Biomechanics

Several large or mid-scale collections of Drosophila enhancer traps have been recently created to allow for genetic swapping of GAL4 coding sequences to versatile transcription activators or suppressors such as LexA, QF, split-GAL4 (GAL4-AD and GAL4-DBD), GAL80 and QS. Yet a systematic analysis of the feasibility and reproducibility of these tools is lacking. Here we focused on InSITE GAL4 drivers that specifically label different subpopulations of olfactory neurons, particularly local interneurons (LNs), and genetically swapped the GAL4 domain for LexA, GAL80 or QF at the same locus. We found that the major utility-limiting factor for these genetic swaps is that many do not fully reproduce the original GAL4 expression patterns. Different donors exhibit distinct efficacies for reproducing original GAL4 expression patterns. The successfully swapped lines reported here will serve as valuable reagents and expand the genetic toolkits of Drosophila olfactory circuit research.

Drosophila olfactory local interneurons (LNs) in the antennal lobe are highly diverse and variable. How and when distinct types of LNs emerge, differentiate, and integrate into the olfactory circuit is unknown. Through systematic developmental analyses, we found that LNs are recruited to the adult olfactory circuit in three groups. Group 1 LNs are residual larval LNs. Group 2 are adult-specific LNs that emerge before cognate sensory and projection neurons establish synaptic specificity, and Group 3 LNs emerge after synaptic specificity is established. Group 1 larval LNs are selectively reintegrated into the adult circuit through pruning and re-extension of processes to distinct regions of the antennal lobe, while others die during metamorphosis. Precise temporal control of this pruning and cell death shapes the global organization of the adult antennal lobe. Our findings provide a road map to understand how LNs develop and contribute to constructing the olfactory circuit., Local interneurons (LNs) in the Drosophila olfactory system are highly diverse. Here, the authors labeled different LN types and described how different LN subtypes are integrated into the developing circuit.

Local interneurons (LNs) in the Drosophila olfactory system exhibit neuronal diversity and variability, yet it is still unknown how these features impact information encoding capacity and reliability in a complex LN network. We employed two strategies to construct a diverse excitatory-inhibitory neural network beginning with a ring network structure and then introduced distinct types of inhibitory interneurons and circuit variability to the simulated network. The continuity of activity within the node ensemble (oscillation pattern) was used as a readout to describe the temporal dynamics of network activity. We found that inhibitory interneurons enhance the encoding capacity by protecting the network from extremely short activation periods when the network wiring complexity is very high. In addition, distinct types of interneurons have differential effects on encoding capacity and reliability. Circuit variability may enhance the encoding reliability, with or without compromising encoding capacity. Therefore, we have described how circuit variability of interneurons may interact with excitatory-inhibitory diversity to enhance the encoding capacity and distinguishability of neural networks. In this work, we evaluate the effects of different types and degrees of connection diversity on a ring model, which may simulate interneuron networks in the Drosophila olfactory system or other biological systems.

The study presents a significant improvement on the performance of dye-sensitized solar cells (DSSCs) through incorporating the crystalline titania chelated by acetic acid (TAc) into the mesoporous TiO2 photoanodes. The effects of TAc on the blocking layer, mesoporous TiO2 layer, and post-treatment have been investigated. The TAc blocking layer displays compact construction, revealing superior response time and resistance to suppress dark current compared to the blocking layer made from titanium(IV) isopropoxide (TTIP). The power conversion efficiency of DSSCs with the TAc treatment can reach as high as 10.49%, which is much higher than that of pristine DSSCs (5.67%) and that of DSSCs treated by TTIP (7.86%). We find that the TAc incorporation can lead to the decrease of charge transfer resistance and the increase of dye adsorption. The result may be attributed to the fact that the TAc possesses high crystallinity, exposed (101) planes, and acid groups chelated on surface, which are favorable for dye attachment and strong bonding at the FTO/TiO2 and the TiO2/TiO2 interfaces, These improvements result in the remarkable increase of photocurrent and thereby that of power conversion efficiency.

The Drosophila olfactory system is an attractive model for exploring the wiring logic of complex neural circuits. Remarkably, olfactory local interneurons exhibit high diversity and variability in their morphologies and intrinsic properties. Although olfactory sensory and projection neurons have been extensively studied of development and wiring; the development, mechanisms for establishing diversity, and integration of olfactory local interneurons into the developing circuit remain largely undescribed. In this review, we discuss some challenges and recent advances in the study of Drosophila olfactory interneurons.

The Drosophila Hedgehog receptor functions to regulate the essential downstream pathway component, Smoothened, and to limit the range of signaling by sequestering Hedgehog protein signal within imaginal disc epithelium. Hedgehog receptor function requires both Patched and Ihog activity, the latter interchangeably encoded by interference hedgehog (ihog) or brother of ihog (boi). Here we show that Patched and Ihog activity are mutually required for receptor endocytosis and degradation, triggered by Hedgehog protein binding, and causing reduced levels of Ihog/Boi proteins in a stripe of cells at the anterior/posterior compartment boundary of the wing imaginal disc. This Ihog spatial discontinuity may contribute to classically defined cell segregation and lineage restriction at the anterior/posterior wing disc compartment boundary, as suggested by our observations that Ihog activity mediates aggregation of otherwise non-adherent cultured cells and that loss of Ihog activity disrupts wing disc cell segregation, even with downstream genetic rescue of Hedgehog signal response., The range of Hedgehog (Hh) signalling in the Drosophila imaginal disc is limited by Hh/receptor degradation at the anterior/posterior (A/P) compartment boundary. Here, the authors show that degradation is mediated by co-receptor proteins Ihog/Boi, whose cell adhesion functions also contribute to A/P cell segregation.

Significance This research reports that reciprocal interactions between Drosophila olfactory neurons and ensheathing glia mediate the formation of neuronal compartments, groups of synapses that are packed into discrete structures called “glomeruli” that carry specific olfactory information. Ensheathing glia respond to a neuronal cue, the FGF Thisbe, to pattern the boundaries of the nascent compartments. Neural compartments, in turn, require such glial barriers to separate themselves from neighboring compartments and thus ensure the correct organization of the olfactory circuit. These findings highlight the importance of glia in the assembly and maintenance of neural circuits and the functions of FGF signaling in these processes., The formation of complex but highly organized neural circuits requires interactions between neurons and glia. During the assembly of the Drosophila olfactory circuit, 50 olfactory receptor neuron (ORN) classes and 50 projection neuron (PN) classes form synaptic connections in 50 glomerular compartments in the antennal lobe, each of which represents a discrete olfactory information-processing channel. Each compartment is separated from the adjacent compartments by membranous processes from ensheathing glia. Here we show that Thisbe, an FGF released from olfactory neurons, particularly from local interneurons, instructs ensheathing glia to wrap each glomerulus. The Heartless FGF receptor acts cell-autonomously in ensheathing glia to regulate process extension so as to insulate each neuropil compartment. Overexpressing Thisbe in ORNs or PNs causes overwrapping of the glomeruli their axons or dendrites target. Failure to establish the FGF-dependent glia structure disrupts precise ORN axon targeting and discrete glomerular formation.

The original version of this Article contained errors in Figs. 4 and 6. In Fig. 4, panel a, text labels UAS-FLP and LexAop2>stop>myr::smGdP-HA were shifted upwards during typesetting of the figure, and in Fig. 6, panel h, the number 15 was incorrectly placed on the heat map scale. These have now been corrected in both the PDF and HTML versions of the Article.

We present evidence for a novel, coupled two-step action of Hedgehog signaling in patterning axon targeting of Drosophila olfactory receptor neurons (ORNs). In the first step, differential Hedgehog pathway activity in peripheral sensory organ precursors creates ORN populations with different levels of the Patched receptor. Different Patched levels in ORNs then determine axonal responsiveness to target-derived Hedgehog in the brain: only ORN axons that do not express high levels of Patched are responsive to and require a second-step of Hedgehog signaling for target selection. Hedgehog signaling in the imaginal sensory organ precursors thus confers differential ORN responsiveness to Hedgehog-mediated axon targeting in the brain. This mechanism contributes to the spatial coordination of ORN cell bodies in the periphery and their glomerular targets in the brain. Such coupled two-step signaling may be more generally used to coordinate other spatially and temporally segregated developmental events.

Local interneurons play essential roles in information processing by neural circuits. Here we present a comprehensive genetic, anatomical, and electrophysiological analysis of local interneurons (LNs) in the Drosophila antennal lobe, the first olfactory processing center in the brain. We find that LNs are diverse in their neurotransmitter profiles, connectivity, and physiological properties. Analysis of >1500 individual LNs reveals major morphological classes characterized by coarsely stereotyped glomerular innervation patterns. Some of these morphological classes exhibit distinct physiological properties. However, the finer-scale connectivity of an individual LN varies considerably across brains and there is notable physiological variability within each morphological or genetic class. Finally, we show that LN innervation requires interaction with olfactory receptor neurons during development, and some individual variability also likely reflects LN-LN interactions. Our results reveal an unexpected degree of complexity and individual variation in an invertebrate neural circuit, a result that creates challenges for solving the Drosophila connectome.

Establishment of planar polarity in the Drosophila compound eye requires precise 90 degrees rotation of the ommatidial clusters during development. We found that the morphogenetic furrow controls the stop of ommatidial rotation at 90 degrees by emitting signals to posterior ommatidial clusters. One such signal, Scabrous, is synthesized in the furrow cells and transported in vesicles to ommatidial row 6-8. Scabrous vesicles are transported through actin-based cellular extensions but not transcytosis. Scabrous functions nonautonomously to control the stop of ommatidial rotation by suppressing nemo activity in the second 45 degrees rotation. We propose that the morphogenetic furrow regulates precise ommatidial rotation by transporting Scabrous and perhaps other factors through actin-based cellular extensions.

Objective.To investigate the relationship among walking speed, exercise capacity, and leg strength in community dwelling stroke subjects and to evaluate which one was the leading determinant factor of them.Design.This is a descriptive, cross-sectional study. Thirty-five chronic stroke patients who were able to walk independently in their community were enrolled. Walking speed was evaluated by using the 12-meter walking test. A maximal exercise test was used to determine the stroke subjects’ exercise capacity. Knee extensor strength, measured as isokinetic torque, was assessed by isokinetic dynamometer.Results.The main walking speed of our subjects was 0.52 m/s. Peak oxygen uptake (VO2peak) was1.21±0.43 L/min. Knee extensor strength, no matter whether paretic or nonparetic side, was significantly correlated to 12-meter walking speed and exercise capacity. Linear regression also showed the strength of the affected knee extensor was the determinant of walking speed and that of the nonparetic knee extensor was the determinant of exercise capacity in community dwelling stroke subjects.Conclusions.Walking speed and peak oxygen uptake were markedly decreased after stroke. Knee extensor strength of nonparetic leg was the most important determinant of exercise capacity of the community-dwelling stroke subjects. Knee extensor strengthening should be emphasized to help stroke patient to achieve optimal community living.

PMA has both mitogenic and antiproliferative effects on human hepatoma Hep3B cells. In response to low PMA concentration (10 nM), Hep3B cells displayed an increasing proliferation potentiation. At high PMA concentration (1 microM) Hep3B cells exhibited modest cytostatic effects. Determinations of protein kinase C (PKC) activity in PMA-treated cells revealed that alterations in PKC activity are associated with proliferative capacity. The decrease in PKC activity mediated by a high dose of PMA was accompanied by cell growth inhibition. Increases in PKC activity mediated by a low dose of PMA were consistent with proliferation stimulation. Immunoblot analysis showed that there are at least six PKC isoenzymes: alpha, delta, epsilon, mu, zeta and iota/lambda, constitutively expressed in Hep3B cells. Cellular fractionation and immunocytochemical staining results demonstrated that both 10 nM and 1 microM PMA treatments induced a marked translocation of PKC-alpha from cytosol to membrane or nuclear fraction within 5-30 min. At the same time PKC-delta and epsilon were translocated from the membrane to nuclear fraction. In addition, prolonged treatment with 1 microM PMA, but not with 10 nM PMA, selectively mediated the down-regulation of these three PKC isoenzymes. The distinct effects of different concentrations of PMA on cell proliferation and PKC-alpha, delta and epsilon isoenzyme modulation support the involvement of these three PKC isotypes in the mechanism of action of Hep3B cells in cell growth events.

SummaryDuring assembly of the Drosophila olfactory circuit, projection neuron (PN) dendrites prepattern the developing antennal lobe before the arrival of axons from their presynaptic partners, the adult olfactory receptor neurons (ORNs). We previously found that levels of transmembrane Semaphorin-1a, which acts as a receptor, instruct PN dendrite targeting along the dorsolateral-ventromedial axis. Here we show that two secreted semaphorins, Sema-2a and Sema-2b, provide spatial cues for PN dendrite targeting. Sema-2a and Sema-2b proteins are distributed in gradients opposing the Sema-1a protein gradient, and Sema-1a binds to Sema-2a-expressing cells. In Sema-2a and Sema-2b double mutants, PN dendrites that normally target dorsolaterally in the antennal lobe mistarget ventromedially, phenocopying cell-autonomous Sema-1a removal from these PNs. Cell ablation, cell-specific knockdown, and rescue experiments indicate that secreted semaphorins from degenerating larval ORN axons direct dendrite targeting. Thus, a degenerating brain structure instructs the wiring of a developing circuit through the repulsive action of secreted semaphorins.

Development of secondary lower extremity lymphedema after cervical cancer is common. However, severe lymphedema of the female genitalia and vesicular cutaneous lymphatic reflux without lower limb lymphedema after treatment of cervical cancer is rare. We report successful complex decongestive physiotherapy (CDP) in a 53-year-old female who developed recurrent folliculitis, lymphocutaneous reflux, warty change of the right labium majora, and lymphedema involving the external genitalia after receiving hysterectomy, pelvic lymph node dissection, and radiation. CDP included skin care, manual lymphatic drainage, exercise, and use of a hip spica bandage and panty girdle garment. Oral antibiotics were prescribed to control the skin infection. Lymphatic discharge and folliculitis were markedly improved after a 3-week course of treatment. Traditional conservative treatment with pneumatic compression and massage is ineffective and not suitable in controlling lymphedema of the external genitalia. Use of CDP may help to relieve the symptoms and recurrent infection in patients with this condition.