Dorsal Area Research Articles

Substantial projections from the lateral division of the lateral habenula to the dorsal raphe nucleus and from the lateral habenula to the contralateral ventral tegmental area

The lateral habenular nucleus (LHb) projects to the dorsal raphe nucleus (DRN) and ventral tegmental area (VTA). Prior studies have reported that the medial division of the LHb (LHb-m) mainly projects to the DRN, while the LHb mainly projects to the ipsilateral VTA; however, due to only a few studies of projection ratio analysis, the degree of projection of minor and major pathways remains unclear, and the potential significance of minor pathways may be overlooked. After injecting the retrograde tracer into the mice DRN, the proportion of labeled neurons was 63.50% in the LHb-m and 36.50% in the lateral division of the LHb (LHb-l). The proportion distributions of labeled neurons were 26.90% in the anterior LHb-m and 73.10% in the posterior LHb-m. When the retrograde tracer was injected into the VTA, the percentage of labeled neurons was 64.85% in the ipsilateral LHb and 35.15% in the contralateral LHb. The number of cells projecting from anterior and posterior ipsilateral LHb-m to the VTA varied among the individual injection sites. Our quantitative analysis with multiple subjects showed that the projections from LHb-l to DRN and from LHb to contralateral VTA were indeed minor pathways, however, they were substantial. These results provide an anatomical basis for the potential importance of minor pathways projected from the LHb to the VTA and DRN and for the difference in the densities of neurons projecting from the anterior and posterior LHb-m to the DRN.

In vivo validation of osteoinductivity and biocompatibility of BMP-2 enriched calcium phosphate cement alongside retrospective description of its clinical adverse events

PurposeAlthough bone morphogenetic protein-2 (BMP-2) possesses potent osteoinductivity, there have been some concerns on the safety of BMP-2 and BMP-2-incorporated bone substitutes used for bone formation. On the other hand, BMP-2-loaded calcium phosphate cement (BMP-2@CPC) has been developed and used for bone regeneration in oral implantology. Therefore, this study aims to investigate this product's biocompatibility and clinical safety after being used in maxillofacial surgery.Materials and methodsA rat model was employed to assess the osteoinduction and biocompatibility of BMP-2@CPC. Further, a retrospective investigation was carried out: 110 patients who received BMP-2@CPC treatment after their maxillofacial surgery were recruited to describe relative adverse events.ResultsIn vivo, BMP-2@CPC showed a significantly higher mean bone volume density and osteoblasts volume density (15 ± 2% and 3 ± 1%)than those of the CPC group (p < 0.05) after being implanted in the dorsal area of rats. Regarding biocompatibility, the mean fibrous tissue volume density was significantly lower in the BMP-2@CPC group (20 ± 5% compared to 31 ± 6%, p = 0.026). The retrospective clinical study showed that only five mild/moderate adverse events were identified in four patients based on the medical records of 110 patients, including swelling, bony mass, and wound dehiscence. This adverse event occurrence was not affected by gender, age, the dose of filled materials, and operations in the study (p > 0.05).ConclusionsBMP-2-loaded CPC has osteoinductivity and more promising biocompatibility than pure CPC. However, its degradation is slower than CPC. The safety of BMP-2-loaded CPC with 0.5 or 1 mg BMP-2 is promising in oral maxillofacial surgery.Clinical implicationsThis study confirmed the promising safety of this BMP-2 incorporated CPC used in dental clinical practice, which can promote its reassuring application for dental implant placement in bone insufficient areas.Graphical

Differential neural mechanisms underlie cortical gating of visual spatial attention mediated by alpha-band oscillations

Selective attention relies on neural mechanisms that facilitate processing of behaviorally relevant sensory information while suppressing irrelevant information, consistently linked to alpha-band oscillations in human M/EEG studies. We analyzed cortical alpha responses from intracranial electrodes implanted in eight epilepsy patients, who performed a visual spatial attention task. Electrocorticographic data revealed a spatiotemporal dissociation between attention-modulated alpha desynchronization, associated with the enhancement of sensory processing, and alpha synchronization, associated with the suppression of sensory processing, during the cue-target interval. Dorsal intraparietal areas contralateral to the attended hemifield primarily exhibited a delayed and sustained alpha desynchronization, while ventrolateral extrastriatal areas ipsilateral to the attended hemifield primarily exhibited an earlier and sustained alpha synchronization. Analyses of cross-frequency coupling between alpha phase and broadband high-frequency activity (HFA) further revealed cross-frequency interactions along the visual hierarchy contralateral to the attended locations. Directionality analyses indicate that alpha phase in early and extrastriatal visual areas modulated HFA power in downstream visual areas, thus potentially facilitating the feedforward processing of an upcoming, spatially predictable target. In contrast, in areas ipsilateral to the attended locations, HFA power modulated local alpha phase in early and extrastriatal visual areas, with suppressed interareal interactions, potentially attenuating the processing of distractors. Our findings reveal divergent alpha-mediated neural mechanisms underlying target enhancement and distractor suppression during the deployment of spatial attention, reflecting enhanced functional connectivity at attended locations, while suppressed functional connectivity at unattended locations. The collective dynamics of these alpha-mediated neural mechanisms play complementary roles in the efficient gating of sensory information.

Using fMRI to examine nonlinear mixed selectivity tuning to task and category in the human brain

Abstract Recent experimental and theoretical work has shown that nonlinear mixed selectivity, where neurons exhibit interaction effects in their tuning to multiple variables (e.g., stimulus and task) plays a key role in enabling the primate brain to form representations that can adapt to changing task contexts. Thus far all such studies have relied on invasive neural recording techniques. In this study, we demonstrate the feasibility of measuring nonlinear mixed selectivity tuning in the human brain noninvasively using fMRI pattern decoding. To do so, we examined the joint representation of object category and task information across human early, ventral stream, and dorsal stream areas while participants performed either an oddball detection task or a one-back repetition detection task on the same stimuli. These tasks were chosen to equate spatial, object-based, and feature-based attention, in order to test whether task modulations of visual representations still occur when the inputs to visual processing are kept constant between the two tasks, with only the subsequent cognitive operations varying. We found moderate but significant evidence for nonlinear mixed selectivity tuning to object category and task in fMRI response patterns in both human ventral and dorsal areas, suggesting that neurons exhibiting nonlinear mixed selectivity for category and task not only exist in these regions, but cluster at a scale visible to fMRI. Importantly, while such coding in ventral areas corresponds to a rotation or shift in the object representational geometry without changing the representational content (i.e., with the relative similarity among the categories preserved), nonlinear mixed selectivity coding in dorsal areas corresponds to a reshaping of representational geometry, indicative of a change in representational content.

The development of the external genitals in female human embryos and foetuses. Part 2: Vaginal vestibule, anal canal, perineal raphe and perineal cutaneous muscles.

Concomitant with the rupture of the cloacal membrane, the perineal skin epithelium thickens (see accompanying article). In this study, we establish in female embryos and foetuses that the thick skin area divides into ventral and dorsal areas at ~14 weeks and gradually becomes restricted to the vaginal vestibule and anal canal thereafter. The dense mesenchymal core of the labia minora, which forms at ~8 weeks, extends dorsally to the anal canal as a midline reinforcement. The skin epithelium overlying this reinforcement is much thinner than the flanking 'thick skin', and is supported by an interrupted basement membrane, which implies epithelial-mesenchymal transformation of the thin midline epithelium and the subsequent establishment of the perineal raphe by the merging of the adjacent thick epithelium. Meanwhile, the anogenital distance in the perineum increases rapidly in length. Perhaps as a consequence, the labia minora cover only the ventral third of the vaginal vestibule at 20 weeks. The endodermal ducts of Bartholin's glands are identifiable at 7 weeks, while acini form at ~12 weeks. The vestibular bulbs become identifiable at ~10 weeks and form vascular networks after ~14.5 weeks. After the rupture of the cloacal membrane, the diameter of the junction of the dorsal cloaca with the anal canal is just a pinhole but widens dorsoventrally after the 7th week. The cutaneous muscles of the perineal area form as a ventrally open U-shaped mesenchymal mass, from which the anal sphincter and bulbospongiosus muscle develop. In conclusion, our findings show that thick skin epithelium persists in the vaginal vestibule and anal canal.

Awake prone positioning and ventilation distribution as assessed by electric impedance tomography in patients with non-COVID-19 acute respiratory failure: A prospective physiology study

BackgroundAwake prone positioning (APP) can reportedly reduce the need for intubation and help to improve the prognosis of patients with acute hypoxemic respiratory failure (AHRF) infected with COVID-19. However, its physiological mechanism remains unknown. In this study, we evaluated the effect of APP on lung ventilation in patients with moderate-to-severe AHRF in an attempt to better understand the effects on ventilation distribution and to prevent intubation in non-intubated patients. MethodsThe prospective study was performed in the Department of Critical Care Medicine at Shanghai General Hospital, China, from January 2021 to November 2022. The study included patients with AHRF (partial pressure of oxygen [PaO2]/inspired oxygen concentration [FiO2] <200 mmHg or oxygen saturation [SpO2]/FiO2 <235) treated with high-flow nasal oxygen. Electrical impedance tomography (EIT) measurements including center of ventilation (COV), global inhomogeneity (GI) index, and regional ventilation delay (RVD) index were performed in the supine position (T0), 30 min after the start of APP (T1), and at 30 min returning to supine position after the APP (T2). Clinical parameters like SpO2, respiratory rate (RR), FiO2, heart rate (HR), and ROX (the ratio of SpO2 as measured by pulse oximetry/FiO2 to RR) were also recorded simultaneously at T0, T1, and T2. To evaluate the effect of the time points on the variables, Mauchly's test was performed for sphericity and repeated measures analysis of variance was applied with Bonferroni's post hoc multiple comparisons. ResultsTen patients were enrolled. The PaO2/FiO2 ratio was (111.4±33.4) mmHg at the time of recruitment. ROX showed a significant increase after initiation of APP {median (interquartile range [IQR]): T0: 7.5 (6.0–10.1) vs. T1: 7.6 (6.4–9.3) vs. T2: 8.3 (7.2–11.0), P=0.043}. RR (P=0.409), HR (P=0.249), and SpO2/FiO2 (P=0.103) did not change significantly during prone positioning (PP). The COV moved from the ventral area to the dorsal area (T0: [48.8±6.2] % vs. T1: [54.8±6.8] % vs. T2: [50.3±6.1] %, P=0.03) after APP. The GI decreased significantly after APP (T0: median=42.7 %, [IQR: 38.3–47.5] % vs. T1: median=38.2 %, [IQR: 34.6–50.7] % vs. T2: median=37.4 %, [IQR: 34.2–41.4] %, P=0.049). RVD (P=0.794) did not change after APP. ConclusionsAPP can improve ventilation distribution and homogeneity of lung ventilation as assessed by EIT in non-intubated patients with AHRF.Trail Registration Chinese Clinical Trial Registry Identifier: ChiCTR2000035895.

Ketorash: An underdiagnosed entity

Ketoacidosis-Induced Prurigo Pigmentosa is a rare, inflammatory disease characterized by pruritic, erythematous papules with a reticulate pattern on the torso and neck. It affects predominantly young adult Asian women with risk factors for metabolic ketosis, such as Diabetes Mellitus, anorexia nervosa, bariatric surgery and ketogenic diet. A 26-year-old female being treated for refractory focal frontal and generalized epilepsy with ketogenic diet for four months was consulted due to a three-month-long dermatosis which started in the anterior and posterior cervical region and progressed towards the dorsal midline area. Skin lesions were papular and erythematous, often merging with a vaguely reticulated pattern. These lesions were highly pruriginous and worsened during periods ofhigher ketonemia. Histological examination of a cutaneous biopsy sample was compatible with Ketorash. The patient suspended ketogenic diet and was medicated with topical erythromycin, with full resolution of the lesions and no recurrences after 8 months.

The Endocannabinoid System of the Nervous and Gastrointestinal Systems Changes after a Subnoxious Cisplatin Dose in Male Rats

Background/Objectives: Cisplatin, a common chemotherapy agent, is well known to cause severe side effects in the gastrointestinal and nervous systems due to its toxic and pro-inflammatory effects. Although pharmacological manipulation of the endocannabinoid system (ECS) can alleviate these side effects, how chemotherapy affects the ECS components in these systems remains poorly understood. Our aim was to evaluate these changes. Methods: Male Wistar rats received cisplatin (5 mg/kg, i.p.) or saline on day 0 (D0). Immediately after, serial X-rays were taken for 24 h (D0). Body weight was recorded (D0, D1, D2 and D7) and behavioural tests were performed on D4. On D7, animals were euthanized, and gastrointestinal tissue, dorsal root ganglia (DRGs) and brain areas were collected. Expression of genes related to the ECS was assessed via Rt-PCR, while LC-MS/MS was used to analyse endocannabinoid and related N-acylethanolamine levels in tissue and plasma. Results: Animals treated with cisplatin showed a reduction in body weight. Cisplatin reduced gastric emptying during D0 and decreased MAGL gene expression in the antrum at D7. Despite cisplatin not causing mechanical or heat sensitivity, we observed ECS alterations in the prefrontal cortex (PFC) and DRGs similar to those seen in other chronic pain conditions, including an increased CB1 gene expression in L4/L5 DRGs and a decreased MAGL expression in PFC. Conclusions: A single dose of cisplatin (5 mg/kg, i.p.), subnoxious, but capable of inducing acute gastrointestinal effects, caused ECS changes in both gastrointestinal and nervous systems. Modulating the ECS could alleviate or potentially prevent chemotherapy-induced toxicity.

PSIX-2 Skin microbial compositions differ among dog body sites and are affected by dietary probiotics

Abstract The study aimed to characterize the skin microbiota across four distinct body sites and investigate the impact of dietary probiotics on the skin microbiota of healthy adult dogs. Healthy adult dogs [n = 60; mean age = 6.2 ± 2.8 yr; mean body weight (BW) = 13.1 ± 4.0 kg] were randomly assigned into three treatment groups and fed for 60 d: a control kibble diet (CON; n = 20; 29.0% crude protein, 10.1% crude fat, 9.9% crude fiber, 7.1% ash, as-fed), CON supplemented with Bifidobacterium longum 548 (CON-B; n = 20), or CON supplemented with Bifidobacterium longum 548 and Lactobacillus rhamnosus 451 (CON-B-L; n = 20). All dogs were individually housed in a temperature- and humidity-controlled research facility. Protocols were approved by the facility’s Institutional Animal Care and Use Committee before the study. On d 60, skin swab samples were collected from the dorsal lumbar area, right axilla, right groin, and right ear concave pinnae of each dog using sterile swabs. These samples were placed into bead tubes and stored at -20°C until analysis. DNA extraction from skin swab samples was followed by sequencing the V4 region of 16S rRNA using Illumina sequencing on a MiSiq. Sequence data were processed through QIIME 2.0, and statistical analysis was performed using R 4.3.1. to test differences between body sites and diets, with a significance threshold set at P &amp;lt; 0.05. The predominant bacterial phyla observed across all body sites were Actinobacteria (40 ± 21.7%), Firmicutes (31.2 ± 17.9 %), Proteobacteria (17.9 ± 13.3%), and Bacteroidetes (6.6 ± 6.1%). Additionally, Acidobacteria, Gemmatimonadetes, and Verrucomicrobia were exclusive to the groin region. Considering data from all body sites, diets affected relative abundances of phyla and genera in dogs. At phylum level, dogs fed the CON-B diet displayed greater (P &amp;lt; 0.05) relative abundance of Actinobacteria compared with those on the CON diet. The CON-B diet also resulted in a greater (P &amp;lt; 0.05) relative abundance of Firmicutes than dogs on either the CON or CON-B-L diets. At genus level, dogs on the CON-B diet showed significantly greater (P &amp;lt; 0.05) relative abundance of Clostridium, Clostridiaceae unclassified, and Lachnospiraceae unclassified compared with the other diet groups. Dogs on the CON diet displayed a greater (P &amp;lt; 0.05) relative abundance of Dietzia compared with those on probiotic-supplemented diets. These findings underscore the variation in skin microbial composition across distinct body sites, contributing valuable data to limited information available on the skin microbiota of dogs. Moreover, consumption of probiotic influenced the skin microbial compositions in dogs, which warrant further studies to elucidate the relationship between probiotics, skin microbiota, and skin health in dogs.

Actinidia chinensis Planch Ameliorates Photoaging in UVB-Irradiated NIH-3T3 Cells and SKH-1 Hairless Mice by Controlling the Reactive Oxygen Species/AKT Pathway.

In this study, we evaluated the antiphotoaging properties of Actinidia chinensis Planch (ACP) and the molecular mechanisms underlying its ability to prevent UVB-mediated photoaging. Administration of the ethanolic extract of ACP (EEACP) to the dorsal area of hairless mice effectively ameliorated UVB-mediated wrinkle formation, epidermal thickening, and loss of lipid droplets in the epidermis. Additionally, the UVB-induced loss of collagen content in the epidermis was significantly attenuated in mouse skin treated with EEACP. The expression of procollagen type 1 and metalloproteinase-1a, which are related to collagen content in the epidermis, was restored by EEACP treatment in UVB-irradiated mice and NIH-3T3 mouse skin fibroblast cells. Interestingly, EEACP effectively ameliorated UVB-induced reactive oxygen species overproduction. Furthermore, the activation/phosphorylation of AKT, rather than mitogen-activated protein kinases, has been identified as a major target of EEACP in preventing UVB-mediated photoaging. Additionally, N-(1 deoxy-1-fructosyl) valine and phenethylamine glucuronide were identified as analytical indicators of EEACP using high-performance liquid chromatography/mass spectrometry. These results suggest that EEACP can be developed as a functional natural agent capable of preventing photoaging by attenuating UVB-induced activation of the reactive oxygen species/AKT pathway.

Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson’s disease model

The differential vulnerability of dopaminergic neurons of the substantia nigra pars compacta (SNc) is a critical and unresolved question in Parkinson´s disease. Studies in mice show diverse susceptibility of subpopulations of nigral dopaminergic neurons to various toxic agents. In the primate midbrain, the molecular phenotypes of dopaminergic neurons and their differential vulnerability are poorly characterized. We performed a detailed histological study to determine the anatomical distribution of different molecular phenotypes within identified midbrain neurons and their selective vulnerability in control and MPTP-treated monkeys. In the ventral tier of the SNc (nigrosome), neurons rich in Aldh1a1 and Girk2 are intermingled, whereas calbindin is the marker that best identifies the most resilient neurons located in the dorsal tier and ventral tegmental area, recapitulating the well-defined dorsoventral axis of susceptibility to degeneration of dopaminergic neurons. In particular, a loss of Aldh1a1+ neurons in the ventral SNc was observed in parallel to the progressive development of parkinsonism. Aldh1a1+ neurons were the main population of vulnerable dopaminergic nigrostriatal-projecting neurons, while Aldh1a1- neurons giving rise to nigropallidal projections remained relatively preserved. Moreover, bundles of entwined Aldh1a1+ dendrites with long trajectories extending towards the substantia nigra pars reticulata emerged from clusters of Aldh1a1+ neurons and colocalized with dense cannabinoid receptor 1 afferent fibers likely representing part of the striatonigral projection that is affected in human disorders, including Parkinson´s disease. In conclusion, vulnerable nigrostriatal-projecting neurons can be identified by using Aldh1a1 and Girk2. Further studies are needed to define the afferent/efferent projection patterns of these most vulnerable neurons.

Accuracy optimized neural networks do not effectively model optic flow tuning in brain area MSTd.

Accuracy-optimized convolutional neural networks (CNNs) have emerged as highly effective models at predicting neural responses in brain areas along the primate ventral stream, but it is largely unknown whether they effectively model neurons in the complementary primate dorsal stream. We explored how well CNNs model the optic flow tuning properties of neurons in dorsal area MSTd and we compared our results with the Non-Negative Matrix Factorization (NNMF) model, which successfully models many tuning properties of MSTd neurons. To better understand the role of computational properties in the NNMF model that give rise to optic flow tuning that resembles that of MSTd neurons, we created additional CNN model variants that implement key NNMF constraints - non-negative weights and sparse coding of optic flow. While the CNNs and NNMF models both accurately estimate the observer's self-motion from purely translational or rotational optic flow, NNMF and the CNNs with nonnegative weights yield substantially less accurate estimates than the other CNNs when tested on more complex optic flow that combines observer translation and rotation. Despite its poor accuracy, NNMF gives rise to tuning properties that align more closely with those observed in primate MSTd than any of the accuracy-optimized CNNs. This work offers a step toward a deeper understanding of the computational properties and constraints that describe the optic flow tuning of primate area MSTd.

Atlas-based structural analysis of prefrontal cortex atrophy in major depressive disorder: Correlations with severity and episode frequency

BackgroundCurrent models of major depressive disorder (MDD) primarily focus on the structural and functional changes in key prefrontal areas responsible for emotional regulation. Among these regions some sections such as the dorsal prefrontal area, has received limited attention regarding its structural abnormalities in MDD. This study aims to evaluate volumetric abnormalities in brain regions associated with markers of depression severity and episode frequency. MethodsThe study included 33 MDD patients and 33 healthy subjects. Using an atlas-based method, we measured the volumes of several key brain regions based on MRI data. The regions of interest included prefrontal and posterior sections of the middle frontal gyrus (MFG) and superior frontal gyrus (SFG). Additionally, we evaluated the volumes of the dorsal anterior cingulate cortex (dACC), perigenual (rostral) anterior cingulate cortex (pgACC), subgenual cingulate cortex (sgACC), posterior cingulate cortex (PCC), hippocampus (HPC), and parahippocampus (paraHPC). Hamilton Depression Scale (HAM-D) scores and count of the depressive episodes of patients were also obtained. A regression analysis with sex as the confounding factor has been made. ResultsAnalysis of covariances, controlling for sex, showed significant atrophy in the sgACC in the depression group: F(1, 63) = 4.013, p = 0.049 (left) and F(1, 63) = 8.786, p < 0.004 (right). Poisson regression, also controlling for sex, found that each additional depressive episode was associated with a significant reduction in left posterior MFG volume (0.952 times, 95 % CI, 0.906 to 1.000; p = 0.049). ConclusionsFindings in this study highlight the structural abnormalities in MDD patients in correlation to either current depression severity or chronicity of the disease.

A new genus of Gyponini (Hemiptera, Cicadellidae, Iassinae) with description of two new species from Brazil and key to genera of the Hecalapona complex

Gracilipona gen. nov. is described and illustrated based on males and females of two new species from Brazil: G. tetrarama sp. nov. (type-species) from the states of Minas Gerais, Paraná, Rio de Janeiro, and Rio Grande do Sul, and G. birama sp. nov. from Bahia State. The new genus differs from other genera of the Hecalapona complex as follows: antennal ledge extending anteriorly below anterior margin of crown, forming an arched carina that connects the antennal ledges medially; pronotum moderately declivous; forewing with extra crossveins on distal third; protibia with dorsal surface flattened but not expanded, with lateral margins carinate; aedeagus with dorsal apodemes strongly developed and divergent and shaft with lateral processes arising from basal third; ovipositor with valvulae expanded subapically; first valvula with dorsal sculptured area short, mostly strigate, areolate near dorsal margin; and second valvula with a few rounded denticles subapically on dorsal margin. An updated key to genera of the Hecalapona complex and a discussion comparing Gracilipona gen. nov. with other related genera are provided.

Musculoskeletal disorders prediagnosis by infrared thermography in CNC machinery operators: Regression models approaches.

Musculoskeletal System Disorders (MSDs) are a group of injuries that represent common occupational diseases and should be evaluated for prevention purposes because an increase has been observed due to the repetitive movements performed in the industry. This research was carried out in a manufacturing industry where metal parts are manufactured, and workers experience back and wrist pain. To prediagnose Musculoskeletal System Disorders (MSDs) and examine the relationship between temperature, demographic, and physiological factors in workers through predictive models, contributing to MSD prevention. Information from 36 operators was used to obtain vital signs and somatometry data, and thermograms of their hands in the dorsal, palmar, and back areas were collected and analyzed to determine the relationship between temperature and demographic and physiological factors. The ergonomic evaluations proved that the operators were at high risk owing to repetitive movements and postures adopted during work. Eighty-six percent of cases with injuries were identified using infrared thermograms, proving their high level of effectiveness. When studying the relationship between temperature behavior during recovery from repetitive activities and demographic and physiological factors, it was determined that age, dominant hand, respiratory frequency, and BMI were the most significant. Nine regression models were obtained, with coefficients of determination between 0.17 and 0.71. The significant factors for worker injuries were age, dominant hand, respiratory rate, and BMI. However, the sample size and variability in work activities should be extended to generalize the findings.

Topical Application of Cha-Koji, Green Tea Leaves Fermented with Aspergillus Luchuensis var Kawachii Kitahara, Promotes Acute Cutaneous Wound Healing in Mice

“Koji” is one of the most well-known probiotic microorganisms in Japan that contribute to the maintenance of human health. Although the beneficial effects of some probiotics on ulcer healing have been demonstrated, there have been no reports on the wound healing effects of koji to date. In the present study, we investigated the effects of “cha-koji”, green tea leaves fermented with Aspergillus luchuensis, on cutaneous wound healing, using a linear incision wound mouse model. Topical application of autoclave-sterilized cha-koji suspension on the dorsal incision wound area healed the wound significantly faster and, notably, with less scarring than did the green tea or the control distilled water treatment. Further in vitro experiments revealed that the accelerated effects of cha-koji could be attributed to its increased anti-bacterial activity, enhanced epidermal cell proliferation and migration, augmented expression of the anti-inflammatory cytokine transforming growth factor-β1, reduced expression of inflammatory cytokine interleukin-6 in macrophages, and decreased endoplasmic reticulum stress. In addition, we conducted a skin sensitizing potential test, which revealed that cha-koji had no adverse effects that posed a sensitizing risk. Thus, cha-koji may have a potent therapeutic effect on cutaneous wound healing, opening up a new avenue for its clinical application as a medical aid.

Comparison of laparoscopic liver resection for the ventral versus the dorsal areas of segment 8.

The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear. We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023. Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences. The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss. B230165 (approved at December 26, 2023).

Surface-Conjugated Galactose on Electrospun Polycaprolactone Nanofibers: An Innovative Scaffold for Uterine Tissue Engineering.

The uterus, a vital organ in the female reproductive system, nurtures and supports developing embryos until maturity. This study focuses on addressing uterine related problems by creating a nanofibrous scaffold to regenerate uterine myometrial tissue, closely resembling the native extracellular matrix (ECM) for enhanced efficacy. To achieve this, we utilized polycaprolactone (PCL) as a biomaterial and employed an electrospinning technique to generate PCL nanofibers in both random and aligned orientations. Due to the inherent hydrophobic nature of PCL nanofibers, a two-step wet chemistry surface modification technique is used, involving the conjugation of galactose onto them. Galactose, a lectin-binding sugar, was chosen to enhance the scaffold's hydrophilicity, thereby improving cell adhesion and fostering l-selectin-based interactions between the scaffold and uterine cells. These interactions, in turn, activated uterine fibroblasts, leading to ECM remodeling. The optimized electrospinning process successfully generated random and aligned nanofibers. Subsequent surface modification was carried out, and the modified scaffold was subjected to various physicochemical characterization, such as the ninhydrin assay, enzyme-linked lectin assay techniques that revealed successful galactose conjugation, and mechanical characterization to assess any changes in material bulk properties resulting from the modification. The tensile strength of random galactose-modified PCL fibers reached 0.041 ± 0.01 MPa, outperforming random unmodified PCL fibers (0.026 ± 0.01 MPa), aligned unmodified PCL fibers (0.011 ± 0.001 MPa), and aligned modified PCL fibers (0.016 ± 0.002 MPa). Cytocompatibility studies with human uterine fibroblast cells showed enhanced viability and proliferation on the modified scaffolds. Initial pilot studies were attempted in the current study involving subcutaneous implantation in the dorsal area of Wistar rats to assess biocompatibility and tissue response before proceeding to intrauterine implantation indicated that the modification did not induce adverse inflammation in vivo. In conclusion, our study introduces a surface-modified PCL nanofibrous material for myometrial tissue engineering, offering promise in addressing myometrial damage and advancing uterine health and reproductive well-being.

Orthostatic Ex-Vivo Lung Perfusion (EVLP): A Proof of Concept.

The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the "Achilles' heel" of the EVLP due to a more fluid accumulation than in the supine standard position.

Exploring the Consistent Roles of Motor Areas Across Voluntary Movement and Locomotion.

Multiple cortical motor areas are critically involved in the voluntary control of discrete movement (e.g., reaching) and gait. Here, we outline experimental findings in nonhuman primates with clinical reports and research in humans that explain characteristic movement control mechanisms in the primary, supplementary, and presupplementary motor areas, as well as in the dorsal premotor area. We then focus on single-neuron activity recorded while monkeys performed motor sequences consisting of multiple discrete movements, and we consider how area-specific control mechanisms may contribute to the performance of complex movements. Following this, we explore the motor areas in cats that we have considered as analogs of those in primates based on similarities in their cortical surface topology, anatomic connections, microstimulation effects, and activity patterns. Emphasizing that discrete movement and gait modification entail similar control mechanisms, we argue that single-neuron activity in each area of the cat during gait modification is compatible with the function ascribed to the activity in the corresponding area in primates, recorded during the performance of discrete movements. The findings that demonstrate the premotor areas' contribution to locomotion, currently unique to the cat model, should offer highly valuable insights into the control mechanisms of locomotion in primates, including humans.