Dilated Spaces Research Articles

Isometries of Lipschitz‐free Banach spaces

AbstractWe describe surjective linear isometries and linear isometry groups of a large class of Lipschitz‐free spaces that includes, for example, Lipschitz‐free spaces over any graph. We define the notion of a Lipschitz‐free rigid metric space whose Lipschitz‐free space only admits surjective linear isometries coming from surjective dilations (i.e., rescaled isometries) of the metric space itself. We show that this class of metric spaces is surprisingly rich and contains all 3‐connected graphs as well as geometric examples such as nonabelian Carnot groups with horizontally strictly convex norms. We prove that every metric space isometrically embeds into a Lipschitz‐free rigid space that has only three more points.

Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins diagnosed at autopsy in association with novel FOXF1 variant

Abstract Introduction/Objective Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACD/MPV) is a rare disorder characterized by abnormal development of the pulmonary vasculature resulting in intractable pulmonary hypertension in neonates. Affected newborns present with progressive hypoxemia that is nearly always fatal. ACD/MPV is typically seen in the setting of other congenital anomalies, including gastrointestinal, genitourinary, and cardiac systems. Although the pathogenesis of ACD/MPV is poorly understood, inactivating mutations in the FOXF1 gene have been implicated. We present a case of ACD/MPV with associated gastrointestinal/cardiac anomalies and a novel heterozygous mutation of FOXF1. Methods/Case Report A complete autopsy was perfomed. Rapid whole exome sequencing of whole blood was done via reference laboratory. Results (if a Case Study enter NA) A 36-week gestational age male was born via cesarean delivery following a pregnancy course complicated by polyhydramnios. The neonate developed respiratory failure requiring intubation and Extracorporeal Membranous Oxygenation (ECMO). Further clinical evaluation revealed a patent foremen ovale and ductus arteriosus with right to left shunting. After 18 days on ECMO, he was transferred to comfort care where he later died. The body was that of a small for gestational age, phenotypic male neonate without gross dysmorphia noted on external examination. Internal examination revealed duodenal atresia, a patent ductus arteriosus and foramen ovale, and heavy, edematous lungs. Histologic examination of the lungs demonstrated prominent congested veins abutting small arteries with medial hypertrophy within shared adventitial sheaths. The interlobar septa contained dilated lymphatic spaces. Airspaces showed a dense neutrophilic exudate. Rapid whole exome sequencing revealed heterozygous mutations in FOXF1 (c.182T>C, p.Ile61Thr), NOTCH1 (c.7495A>C, p.Ser2499Arg) and a hemizygous mutation in SSR4 (c.20G>T, p.Gly7Val). The FOXF1 mutation was predicted to be damaging and has not yet been reported in the literature; however, its clinical significance was interpreted as uncertain. The significance of the NOTCH1 and SSR4 mutations were considered unknown. Given these findings, a diagnosis of ACD/MPV was given as the cause of death. Conclusion This case illustrates the classic clinical, gross and histologic findings described in ACD/MPV. Additionally, a novel heterozygous mutation of FOXF1 was identified and predicted to be damaging, supporting the role of FOXF1 mutations in the pathogenesis of ACD/MPV.

Hydrops regression after vestibular denervation - longitudinal magnetic resonance study in patients with severe Meniere's disease treated with vestibular neurectomy.

The aim was to evaluate endolymphatic hydrops in patients with severe Ménière's disease (MD) before and after vestibular neurectomy to verify if vestibular denervation results in hydrops regression. Magnetic resonance imaging was performed after intravenous gadolinium injection in twenty patients with unilateral definite MD before and after the vestibular neurectomy. Clinical symptoms and audiovestibular tests were evaluated. Follow-up intervals ranged from 18 to 35 months after the surgery. Endolymphatic hydrops were visualized in all patients in the preoperative scans. After the vestibular neurectomy, all patients presented a complete resolution of vertigo episodes. Regression of the endolymphatic hydrops was observed in 35% and 15% of cases analyzing cochlea and vestibule, respectively. In 71.43% of patients with utricular herniation into the lateral semicircular canal, withdrawal of the hernia was visualized. Asymmetrical contrast enhancement in the cochlea regressed in 17.64% of cases. Analyzing all the parameters collectively, in 60% of patients, partial regression of at least one of the radiological signs was confirmed in the follow-up examination. No progression of the endolymphatic hydrops was visualized after the surgery in either the cochlea or the vestibule. Vestibular neurectomy is an effective treatment, eliminating vertigo attacks and improving the quality of life in patients with MD. Magnetic resonance imaging of the inner ear allows visualization of changes in endolymphatic hydrops degree after treatment. Regression of the endolymphatic hydrops after vestibular neurectomy suggests that vestibular denervation may effectively halt the progression of the endolymphatic space dilatation and result in hydrops regression.

ELUCIDATING THE EFFECTS OF FORMALIN AS FOOD PRESERVATIVE ON GROSS AND HISTOARCHITECTURE OF VITAL ORGANS OF SWISS ALBINO MICE

Formalin usage as food preservative in Bangladesh has dramatically increased recently, especially in fish, fruits, and many other food products, putting the vast majority of people in serious health risk. With this background, the study was aimed to detect the alterations of gross structure and histoarchitecture of vital organs in Swiss albino mice due to the consumption of formalin. Mice were divided into five groups at the age of four weeks. Normal drinking water was supplied to the control group of mice. Mice of group 1, 2, 3 and 4 were supplied normal drinking water mixed with formalin at 1%, 5%, 10% and 20% concentrations, respectively up to week 24. Mice treated with varying concentrations of formalin for 24 weeks was assessed for the weight change of their liver, heart, kidney and lung weights. Investigations were also conducted on histological alterations in the liver, heart, kidney and lung. After 24 weeks of treatment of mice with different concentrations of formalin, the weight of all four major organs (liver, heart, kidney and lung) was decreased in all formalin-treated mice in comparison to control mice. Petechial hemorrhages, congestion, necrosis, and parenchymatous cell degeneration have been found in liver. Kidney sections have shown decreased Bowman’s space, hypertrophied glomerulus and tubular dilatation. Leucocyte infiltration, necrosis, and rupture of connective tissue have been seen in the heart sections. Lung sections have shown pulmonary alterations, including hemorrhages, thicker alveolar walls, and inflammatory cells. It was, concluded that formalin has adverse effects on vital organs of Swiss Albino mice.

Biochanin A Has Protective and Therapeutic Effects against Li2CO3-induced Nephrotoxicity in Rats Model

BACKGROUND: Long-term usage of lithium carbonate (Li2CO3) as treatment of bipolar disorder might cause nephrotoxicity. Li2CO3-induced nephrotoxicity usually treated by renal dialysis, which is quite expensive. Usage of natural products that possess anti-inflammatory and antioxidant properties as biochanin A (BCA) may be useful against Li2CO3 nephrotoxicity. Therefore, this study was conducted to evaluate Li2CO3 nephrotoxic effects and BCA therapeutic and protective effects against it.METHODS: Twenty-eight rats divided into 4 groups: negative control (NC), Li2CO3, Li2CO3 + BCA therapeutic, and BCA + Li2CO3 protective group. Complete blood picture, serum kidney function tests (urea, creatinine, and cystatin C) and kidney tissue homogenate oxidative stress index as malonaldehyde (MDA), superoxide dismutase (SOD), glutathione S-transferase (GST) and catalase (CAT) were measured using enzyme linked immunosorbent assay (ELISA) methods. While, kidney histopathological changes were evaluated under light microscope.RESULTS: Li2CO3 administration elicited significant changes in hematological parameters as hypochromic anemia, decreased platelets and leukocytosis. Serum urea, creatinine and cystatin C were elevated. Renal homogenate analysis revealed significant elevation of MDA and decline in GST, CAT, SOD levels. Kidney histopathology analysis revealed hemorrhage between renal tubules, glomerular capillaries congestion, Bowman’s space dilatation, structural alterations in renal tubules cells include loss of brush border, deeply stained nuclei and elevated in size and number of cytoplasmic vacuoles. Therapeutic and protective groups of BCA showed amelioration of hematological alteration, kidney functions, oxidative stress markers and restoration of kidney tissues.CONCLUSION: BCA has both protective and therapeutic effects against Li2CO3-induced nephrotoxicity possibly through the reduction of oxidative stress.KEYWORDS: biochanin A, hematological changes, kidney, lithium carbonate salt, oxidative stress, protective effects, therapeutic effects

Quantum simulation of dissipation for Maxwell equations in dispersive media

The dissipative character of an electromagnetic medium breaks the unitary evolution structure that is present in lossless, dispersive optical media. In dispersive media, dissipation appears in the Schrödinger representation of classical Maxwell equations as a sparse diagonal operator occupying an r-dimensional subspace. A first order Suzuki-Trotter approximation for the evolution operator enables us to isolate the non-unitary operators (associated with dissipation) from the unitary operators (associated with lossless media). The unitary operators can be implemented through qubit lattice algorithm (QLA) on n qubits, based on the discretization and the dimensionality of the pertinent fields. However, the non-unitary-dissipative part poses a challenge both physically and computationally on how it should be implemented on a quantum computer. In this paper, two probabilistic dilation algorithms are considered for handling the dissipative operators. The first algorithm is based on treating the classical dissipation as a linear amplitude damping-type completely positive trace preserving (CPTP) quantum channel where an unspecified environment interacts with the system of interest and produces the non-unitary evolution. Therefore, the combined system-environment is now closed, and must undergo unitary evolution in the dilated space. The unspecified environment can be modeled by just one ancillary qubit, resulting in an implementation scaling of O(2n−1n2) elementary gates for the total system-environment unitary evolution operator. The second algorithm approximates the non-unitary operators by the Linear Combination of Unitaries (LCU). On exploiting the diagonal structure of the dissipation, we obtain an optimized representation of the non-unitary part, which requires O(2n) elementary gates. Applying the LCU method for a simple dielectric medium with homogeneous dissipation rate, the implementation scaling can be further reduced into O[poly(n)] basic gates. For the particular case of weak dissipation we show that our proposed post-selective dilation algorithms can efficiently delve into the transient evolution dynamics of dissipative systems by calculating the respective implementation circuit depth. A connection of our results with the non-linear-in-normalization-only (NINO) quantum channels is also presented.

Higher intracranial arterial pulsatility is associated with presumed imaging markers of the glymphatic system: An explorative study

BackgroundArterial pulsation has been suggested as a key driver of paravascular cerebrospinal fluid flow, which is the foundation of glymphatic clearance. However, whether intracranial arterial pulsatility is associated with glymphatic markers in humans has not yet been studied. MethodsSeventy-three community participants were enrolled in the study. 4D phase-contrast magnetic resonance imaging (MRI) was used to quantify the hemodynamic parameters including flow pulsatility index (PIflow) and area pulsatility index (PIarea) from 13 major intracerebral arterial segments. Three presumed neuroimaging markers of the glymphatic system were measured: including dilation of perivascular space (PVS), diffusivity along the perivascular space (ALPS), and volume fraction of free water (FW) in white matter. We explored the relationships between PIarea, PIflow, and the presumed glymphatic markers, controlling for related covariates. ResultsPIflow in the internal carotid artery (ICA) C2 segment (OR, 1.05; 95 % CI, 1.01–1.10, per 0.01 increase in PI) and C4 segment (OR, 1.05; 95 % CI, 1.01–1.09) was positively associated with the dilation of basal ganglia PVS, and PIflow in the ICA C4 segment (OR, 1.06, 95 % CI, 1.02–1.10) was correlated with the dilation of PVS in the white matter. ALPS was associated with PIflow in the basilar artery (β, -0.273, p, 0.046) and PIarea in the ICA C2 (β, -0.239, p, 0.041) and C7 segments (β, -0.238, p, 0.037). Conclusions: Intracranial arterial pulsatility was associated with presumed neuroimaging markers of the glymphatic system, but the results were not consistent across different markers. Further studies are warranted to confirm these findings.

Perivascular Space Burden and Cerebrospinal Fluid Biomarkers in US Veterans With Blast-Related Mild Traumatic Brain Injury.

Blast-related mild traumatic brain injury (mTBI) is recognized as the "signature injury" of the Iraq and Afghanistan wars. Sleep disruption, mTBI, and neuroinflammation have been individually linked to cerebral perivascular space (PVS) dilatation. Dilated PVSs are putative markers of impaired cerebrospinal fluid (CSF) and interstitial fluid exchange, which plays an important role in removing cerebral waste. The aim of this cross-sectional, retrospective study was to define associations between biomarkers of inflammation and MRI-visible PVS (MV-PVS) burden in Veterans after blast-related mTBI (blast-mTBI) and controls. The CSF and plasma inflammatory biomarker concentrations were compared between blast-mTBI and control groups and correlated with MV-PVS volume and number per white matter cm3. Multiple regression analyses were performed with inflammatory biomarkers as predictors and MV-PVS burden as the outcome. Correction for multiple comparisons was performed using the Banjamini-Hochberg method with a false discovery rate of 0.05. There were no group-wise differences in MV-PVS burden between Veterans with blast-mTBI and controls. Greater MV-PVS burden was significantly associated with higher concentrations of several proinflammatory biomarkers from CSF (i.e., eotaxin, MCP-1, IL-6, IL-8) and plasma (i.e., MCP-4, IL-13) in the blast-mTBI group only. After controlling for sleep time and symptoms of post-traumatic stress disorder, temporal MV-PVS burden remained significantly associated with higher CSF markers of inflammation in the blast-mTBI group only. These data support an association between central, rather than peripheral, neuroinflammation and MV-PVS burden in Veterans with blast-mTBI independent of sleep. Future studies should continue to explore the role of blast-mTBI related central inflammation in MV-PVS development, as well as investigate the impact of subclinical exposures on MV-PVS burden.

The Space Dilation: Analyzing Progressive Speed Reduction and Its Relativistic Parallels

The Space Dilation: Analyzing Progressive Speed Reduction and Its Relativistic Parallels

Saroglitazar suppresses KIM-1 and type IV collagen in high fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats.

Nephropathy is the most common comorbidity linked to T2D. The present study aimed to examine the potential of saroglitazar in the context of a high-fat diet and low-dose streptozotocin-induced diabetic nephropathy in Wistar rats. Molecular docking simulation investigations were conducted on the ligand-binding region of type IV collagen and Kidney injury molecule-1 (KIM-1), using saroglitazar and fenofibrate as the subjects. The rats were fed either a conventional rodent diet or a high-fat diet ad libitum for two weeks. Following a two-week period, the rats given an HFD were administered with a low-dose of STZ (35 mg/kg, IP). Rats with experimentally induced diabetes were categorized into five groups: normal control; diabetic control; HFD+STZ+saroglitazar (2 mg/kg); HFD+STZ+saroglitazar (4 mg/kg); HFD+STZ+fenofibrate (100 mg/kg) treated orally for 21 days with continuation on HFD. After 21 days, rats were kept on fasting overnight, blood and urine was acquired for various biochemical analysis. Animals were sacrificed, and kidney tissues were removed for histopathological studies. In-silico investigation showed a substantial affinity between saroglitazar and fenofibrate with KIM-1 and type IV collagen. Saroglitazar produced a significant (P<0.01) reduction in weight of the body, serum blood sugar, albumin, creatinine, and BUN levels. Further, saroglitazar significantly (P<0.01) reduced the KIM-1 and type IV collagen levels in the urine of diabetic rats. Histopathological results showed improvement in tubular degeneration, necrosis, and dilatation of Bowman's space in kidney tissue. Saroglitazar attenuated renal injury by improving renal function in HFD+STZ-induced DN in Wistar rats.

Comprometimento cognitivo vascular e demência: uma revisão narrativa

ABSTRACT Vascular cognitive impairment (VCI) is the second most common cause of cognitive impairment after Alzheimer's disease. The VCI spectrum involves a decline in cognition attributable to vascular pathologies (e.g., large infarcts or hemorrhages, microinfarcts, microbleeds, lacunar infarcts, white matter hyperintensities, and perivascular space dilation). Pathophysiological mechanisms include direct tissue injury, small vessel disease, inflammaging (inflammation + aging), atrophy, and altered neurotransmission. VCI is diagnosed using distinct clinical and radiological criteria. It may lead to long-term disability and reduced quality of life. An essential factor for reducing cognitive impairment incidence is preventing stroke by managing traditional and non-traditional cerebrovascular risk factors. This article reviews the spectrum of VCI, epidemiology, risk factors, pathophysiology, diagnosis, available treatment, and preventive strategies.

The role of pomegranate seed oil on kidney and lung tissues in the treatment of sepsis: animal pre-clinical research.

Sepsis is a common disease with a high mortality. Decreasing the speed is possible with early and intensive therapy. However, most medicines have been tested, but none has proven effective. Therefore, the study aimed to discover the protective and therapeutic effects of pomegranate seed oil (PSO). The cecal ligation puncture (CLP) method was used to induce sepsis. The experimental procedure was started with the animals divided haphazardly into four groups: control (C), sepsis (CLP), CLP + low dose PSO (CLP + LD), and CLP + high dose PSO (CLP + HD). First, the cecum was filled with feces. The full cecum was tied under the ileocecal valve for ligation and punctured. At 1 hour after CLP, 0.32 mg/kg and 0.64 mg/kg of PSO were administered. 24 hours after, lung and kidney specimens were collected. Neutrophil infiltration/aggregation and alveolar wall thickness decreased in lung with PSO groups compared with the CLP. The findings for overall lung injury were similar. In renal, all parameters were increased in the CLP compared with C, except for vascular vacuolization and hypertrophy. According to the CLP, all parameters were significantly lower in CLP + HD. Furthermore, glomerular vacuolization, degeneration, and necrosis of tubular cell, dilatation of bowman space, and tubular hyaline cylinders reduced CLP + LD versus CLP. Thiobarbituric acid-reactive substances decreased in lung, with the PSO groups. In addition, superoxide dismutase increased in PSO groups versus CLP. We conclude that the high-dose PSO is especially effective in treating sepsis.

PKCε activator protects hippocampal microvascular disruption and memory defect in 3×Tg-Alzheimer's disease mice with cerebral microinfarcts.

Current evidence suggests that microvessel disease is involved in Alzheimer's disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs. To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 months old were examined for confocal immunohistochemistry at a single cell or microvessel level in the hippocampal CA1 area, important for spatial memory storage, and in the dorsal hippocampus by western blots. In 3×Tg mice without cerebral microinfarcts, an accelerating age-related increase in (mild) oxidative stress and hypoxia inducible factor (HIF)-1α, but a reduction in VEGF, mitochondrial transcription factor A (TFAM), and MnSOD were associated with capillary loss. The change was less pronounced in arterioles. However, in 3×Tg mice with cerebral microinfarcts, increasing arteriolar diameter and their wall cells were related with the strong oxidative DNA damage 8-hydroxy-2'-deoxyguanosine (8-OHdG), apoptosis (cleaved caspase 3), and sustained hypoxia (increased HIF-1α and VEGF/PKCε/extracellular signal regulated kinase or ERK pathway). Microocclusion enhanced the loss of the synaptic marker spinophilin, astrocytic number, and astrocyte-vascular coupling areas and demyelination of axons. DCPLA-ME prevented spatial memory defect; strong oxidative stress-related apoptosis; sustained hypoxia (by reducing HIF-1α and VEGF); and exaggerated cell repair in arteriolar walls, pericapillary space dilation, neuro-glial-vascular disruption, and demyelination. In conclusion, in 3×Tg mice with cerebral microinfarcts, sustained hypoxia (increased HIF-1α and VEGF signals) is dominant with arteriolar wall thickening, and DCPLA has a protective effect on sustained hypoxia.

Neochloris aquatica induces larval mortality, molting defects, and unstable flightless adults in the Asian tiger mosquito

The Asian tiger mosquito, Aedes albopictus, is a highly invasive and aggressive species capable of transmitting a large number of etiological agents of medical and veterinary importance, posing a high risk for the transmission of emerging viruses between animals and humans. In this work, we evaluated the mosquitocidal activity of Neochloris aquatica against A. albopictus throughout its development and analyzed whether this effect was potentiated when the microalga was cultivated under stress conditions due to nutrient deprivation. Our results suggest that N. aquatica produces metabolites that have negative effects on these insects, including larval mortality, interruption of pupal development, and incomplete emergence of adults when fed on microalgae in the larval stages. When microalgae were cultured under stress conditions, an increase in molting defects was recorded, and the number of healthy adults emerged drastically decreased. Histological studies revealed severe signs of total disintegration of different tissues and organs in the thorax and abdomen regions. The muscles and fat bodies in the midgut and foregut were severely distorted. In particular, larval intestinal tissue damage included vacuolization of the cytoplasm, destruction of brush border microvilli, and dilation of the intercellular space, which are distinctive morphological characteristics of apoptotic cells. Evidence suggests that N. aquatica produces metabolites with mosquitocidal effects that affect development and, therefore, the ability to vector etiological agents of medical and veterinary importance.

Hypoxia-inducible microRNA-155 negatively regulates epithelial barrier in eosinophilic esophagitis by suppressing tight junction claudin-7.

MicroRNA (miRNA)-mediated mRNA regulation directs many homeostatic and pathological processes, but how miRNAs coordinate aberrant esophageal inflammation during eosinophilic esophagitis (EoE) is poorly understood. Here, we report a deregulatory axis where microRNA-155 (miR-155) regulates epithelial barrier dysfunction by selectively constraining tight junction CLDN7 (claudin-7). MiR-155 is elevated in the esophageal epithelium of biopsies from patients with active EoE and in cell culture models. MiR-155 localization using insitu hybridization (ISH) in patient biopsies and intra-epithelial compartmentalization of miR-155 show expression predominantly within the basal epithelia. Epithelial miR-155 activity was evident through diminished target gene expression in 3D organotypic cultures, particularly in relatively undifferentiated basal cell states. Mechanistically, generation of a novel cell line with enhanced epithelial miR-155 stable overexpression induced a functionally deficient epithelial barrier in 3D air-liquid interface epithelial cultures measured by transepithelial electrical resistance (TEER). Histological assessment of 3D esophageal organoid cultures overexpressing miR-155 showed notable dilated intra-epithelial spaces. Unbiased RNA-sequencing analysis and immunofluorescence determined a defect in epithelial barrier tight junctions and revealed a selective reduction in the expression of critical esophageal tight junction molecule, claudin-7. Together, our data reveal a previously unappreciated role for miR-155 in mediating epithelial barrier dysfunction in esophageal inflammation.

Examination of the traction effect in an artificial muscle-type dynamic traction orthosis using computed tomography.

Dart-throwing motion from radial dorsiflexion to palmar flexion has recently attracted attention as a functional movement direction of the wrist joint. We developed a novel artificial muscle-type dynamic traction orthosis (DTSaM) that includes these movements. This prospective crossover controlled study aimed to compare the traction effects in the presence and absence of DTSaM using computed tomography. Healthy participants with no history of finger disease (6 men: 6 fingers, 4 women: 4 fingers; average age [range]: 29.4 [34-24] years) were examined. The distance and area of the joint space between the radiolunate (RL) and capitolunate (CL) joints were evaluated using 2 types of computed tomography: automatic movement and DTSaM. Participants with DTSaM showed more dilated joint space distance on the dorsal and central sides (p < 0.05) and larger joint space areas on the dorsal side (p < 0.05) of the RL and CL joints than those without orthosis. Significant differences in the magnitude of change in each joint were observed between the RL and CL joints regarding the joint space distance on the dorsal (p = 0.021) and central (p = 0.038) sides and the joint space area on the dorsal side (p = 0.044). The movement of the CL joint is important in the dorsiflexion direction. Our results suggest that the dilated CL joint allows dorsiflexion and that combined traction and dart-throwing motion exercises may be possible for wrist joint contracture.

Congenital Pulmonary Airway Malformation Type 1 with Pulmonary Neuroendocrine Cell Hyperplasia in an Adult Male: a Rare Case Report

Abstract Introduction/Objective Congenital pulmonary airway malformations (CPAM) is rare, usually diagnosed in the pediatric population, and may occur in adults. Pulmonary neuroendocrine cell hyperplasia (PNECH) mimicking diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) associated with CPAM has not been described previously. We report a case of CPAM Type 1 with PNECH. Methods/Case Report A 33-year-old male, with past medical history of latent tuberculosis (TB) by Quantiferon blood testing, recurrent pneumonia, recurrent lung abscesses, and lung cavitary lesion for three years, presented with fever, cough with hemoptysis, shortness of breath, and left-sided chest pain. Computerized tomography of chest displayed a 10.8 cm cavitary lesion in the left lower lobe of the lung. The patient underwent left lower lobectomy of the lung. Grossly, the lobectomy specimen revealed a 10.5 cm irregular cavity communicating to the superior segmental bronchus of the left lower lobe. Microscopically, the dominant large cyst was surrounded by lung parenchyma and small cystically dilated spaces resembling bronchioles under the fibrotic pleura. The large cyst was lined by respiratory epithelium with rare pathognomonic mucous cells in clusters. Cyst walls contained smooth muscle, small islands of cartilage, and focal intense acute and chronic inflammatory cell infiltrates with hemorrhage. There were multiple foci of proliferation of pulmonary neuroendocrine cells centered around bronchioles surrounding the large cyst. The neuroendocrine cells were arranged from individual cells and cellular aggregates to larger tumorlets, highlighted by Synaptophysin and Chromogranin immunostains. No granuloma or necrosis was present. No acid-fast bacilli or fungal microorganisms were identified by special stains. The findings are consistent with CPAM type 1, with PNECH. Results (if a Case Study enter NA) NA Conclusion Our study demonstrates a histologically diagnosed adult congenital pulmonary airway malformations type 1 with an incidental pulmonary neuroendocrine cell hyperplasia, which mimics diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. To the best of our knowledge, this is the first report of such an association.

Cerebrospinal fluid efflux through dynamic paracellular pores on venules as a missing piece of the brain drainage system

AbstractThe glymphatic system plays a key role in the clearance of waste from the parenchyma, and its dysfunction has been associated with the pathogenesis of Alzheimer's disease (AD). However, questions remain regarding its complete mechanisms. Here, we report that efflux of cerebrospinal fluid (CSF)/interstitial fluid (ISF) solutes occurs through a triphasic process that cannot be explained by the current model, but rather hints at the possibility of other, previously undiscovered routes from paravenous spaces to the blood. Using real‐time, in vivo observation of efflux, a novel drainage pathway was discovered, in which CSF molecules enter the bloodstream directly through dynamically assembled, trumpet‐shaped pores (basolateral ϕ&lt;8 μm; apical ϕ &lt; 2 μm) on the walls of brain venules. As Zn2+ could facilitate the brain clearance of macromolecular ISF solutes, Zn2+‐induced reconstruction of the tight junctions (TJs) in vascular endothelial cells may participate in pore formation. Thus, an updated model for glymphatic clearance of brain metabolites and potential regulation is postulated. In addition, deficient clearance of Aβ through these asymmetric venule pores was observed in AD model mice, supporting the notion that impaired brain drainage function contributes to Aβ accumulation and pathogenic dilation of the perivascular space in AD.

Electroacupuncture improves cognitive dysfunction in rats with Alzheimer's disease by regulating microglial cells.

To observe the effect of electroacupuncture (EA) on microglia (MG), Janus kinase-2 (JAK2) and signal transducer and activator of transcription-3 (STAT3) in hippocampal CA1 region of Alzheimer's di-sease (AD) rats, so as to explore its mechanisms in the treatment of AD. Thirty-six male SD rats were randomly divided into sham operation, model and EA groups, with 12 rats in each group. The AD rat model was established by intraperitoneal injection of D-galactose combined with intrahippocampal injection of aggregated Aβ25-35. The rats in the EA group were given EA (2 Hz/20 Hz, 2 mA) at "Baihui"(GV20) and"Shenting"(GV24) for 30 min, once daily, 6 days a week for 4 weeks. Morris water maze test was used to detect the learning and memory ability and spatial exploration ability of rats. HE staining was used to observe the pathological changes of hippocampus. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The positive expression of MG marker io-nized calcium adaptor protein (Iba-1) in hippocampus was observed by immunofluorescence staining. The expression levels of serum inflammatory factor interferon-γ (IFN-γ) and transforming growth factor beta 1 (TGF-β1) were detected by ELISA. The mRNA expression levels of JAK2, STAT3, inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in hippocampal CA1 region were detected by real-time quantitative PCR. The protein and phosphorylation levels of JAK2 and STAT3 in hippocampal CA1 region were detected by Western blot. Compared with the sham operation group, the escape latency of the model group was significantly prolonged (P<0.01), and the number of crossing the original platform was significantly reduced (P<0.01), the positive expression of Iba-1 in CA1 region, the content of serum IFN-γ, the relative mRNA expressions of JAK2, STAT3 and iNOS, and the protein and phosphorylation levels of JAK2 and STAT3 were significantly increased (P<0.01), while the content of serum TGF-β1 and the relative expression of Arg-1 mRNA were significantly decreased (P<0.01). Compared with the model group, the escape latency of rats in the EA group was significantly shortened (P<0.01), the number of crossing the original platform was significantly increased (P<0.01), the positive expression of Iba1, the content of serum IFN-γ, the mRNA expressions of JAK2, STAT3 and iNOS, and the protein and phosphorylation levels of JAK2 and STAT3 were significantly decreased (P<0.05, P<0.01), while the content of serum TGF-β1 and the expression of Arg-1 mRNA were significantly increased (P<0.01). Moreover, pathological and ultrastructural observation showed a reduction in the number of hippocampal neurons, changement of nuclear morphology, dilation of intercellular space, and decreased number of mitochondria in the model group；these situations were relatively milder in the EA group. EA can improve the learning and memory function of AD rats, which may be associated with its functions in decreasing MG activities, and inhibiting the JAK2 / STAT3 signaling pathway in the hippocampus.

High‐precision real‐time urine crystallization recognition based on dilated bilinear space pyramid ConvNext

AbstractUrinary sediment image detection, as one of the three major routine clinical tests in medical practice, is an important method for physical examination and diagnosis of urinary system diseases. Crystalluria detection is a subtask of urinary sediment image detection, focusing on detecting and identifying crystalline components in urine. To address the issues of low accuracy and inefficiency caused by small crystal granularity in crystalluria detection, we propose the Dilated Bilinear Space Pyramid ConvNext Network (DBSPC‐Net), which achieves high‐precision real‐time crystalluria detection. DBSPC‐Net ingeniously combines dilated convolution pooling with bilinear space pyramid, introducing Dilated Bilinear Space Pyramid Pooling (DBSPP) to enlarge the receptive field and capture information at multiple scales. Additionally, we utilize the Normalized Gaussian Wasserstein Distance Loss (NWDLoss) instead of Intersection over Union (IoU) to enhance the recognition of small targets. Finally, the ConvNext module is employed to fuse local and global features, enhancing urine crystal recognition accuracy and speed. The crystalluria dataset is sourced from 400 actual patients in a hospital. It comprises five main types of urine crystals, namely calcium oxalate dihydrate, calcium oxalate monohydrate, uric acid, ammonium magnesium phosphate, and cystine. Experimental results demonstrate that the proposed improved model achieves an average precision of 87.34% and a detection time of 7.9 ms per urine crystal image. DBSPC‐Net can accurately and rapidly identify crystalluria objects in scenarios involving microscope mica compensation, meeting the requirements of algorithmic detection accuracy and real‐time performance in crystalluria detection.