The matricellular protein CCN3 supports lung endothelial homeostasis and function.

Aberrant vascular remodeling contributes to the progression of many aging-associated diseases, including idiopathic pulmonary fibrosis (IPF), where heterogeneous capillary density, endothelial transcriptional alterations, and increased vascular permeability correlate with poor disease outcomes. Thus, identifying disease-driving mechanisms in the pulmonary vasculature may be a promising strategy to limit IPF progression. Here, we identified Ccn3 as an endothelial-derived factor that is upregulated in resolving but not in persistent lung fibrosis in mice, and whose function is critical for vascular homeostasis and repair. Loss and gain of function experiments were carried out to test the role of CCN3 in lung microvascular endothelial function in vitro through RNAi and the addition of recombinant human CCN3 protein, respectively. Endothelial migration, permeability, proliferation, and in vitro angiogenesis were tested in cultured human lung microvascular endothelial cells (ECs). Loss of CCN3 in lung ECs resulted in transcriptional alterations along with impaired wound-healing responses, in vitro angiogenesis, barrier integrity as well as an increased profibrotic activity through paracrine signals, whereas the addition of recombinant CCN3 augmented endothelial function. Altogether, our results demonstrate that the matricellular protein CCN3 plays an important role in lung endothelial function and could serve as a promising therapeutic target to facilitate vascular repair and promote lung fibrosis resolution.

Impairment of Nrf2- and Nitrergic-Mediated Gastrointestinal Motility in an MPTP Mouse Model of Parkinson's Disease.

BACKGROUND: Gastrointestinal (GI) motility dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Studies have indicated that GI motility functions are impaired before the onset of PD. AIMS: To investigate the underlying mechanism of PD-induced GI dysmotility in MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine)-induced animal model. METHODS: C57BL/6 mice were administered with or without a selective dopamine neurotoxin, MPTP, to induce parkinsonian symptoms. In addition to in vivo studies, in vitro experiments were also conducted in colon specimens using l-methyl-4-phenylpyridinium (MPP+), a metabolic product of MPTP. Gastric emptying, colon motility, nitrergic relaxation, and western blot experiments were performed as reported. RESULTS: MPTP-induced PD mice showed decreased expression of nuclear factor erythroid 2-related factor (Nrf2) and its target phase II genes in gastric and colon neuromuscular tissues. Decreased levels of tetrahydrobiopterin (BH4, a critical cofactor for nNOS dimerization) associated with uncoupling of nNOS in gastric and colon tissues exposed to MPTP. Impaired enteric nitrergic system led to delayed gastric emptying and slower colonic motility compared to the control mice. In vitro results in colon specimens confirm that activation of Nrf2 restored MPP+-induced suppression of alpha-synuclein, tyrosine hydroxylase (TH), Nrf2, and heme oxygenase-1. In vitro exposure to L-NAME [N(w)-nitro-L-arginine methyl ester], a NOS synthase inhibitor, reduced protein expression of TH in colon tissue homogenates. CONCLUSIONS: Loss of Nrf2/BH4/nNOS expression in PD impairs antioxidant gene expression, which deregulates NO synthesis, thereby contributing to the development of GI dysmotility and constipation. Nitric oxide appears to be important to maintain dopamine synthesis in the colon.

Extranodal follicular dendritic cell sarcoma involving tonsil.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm arising from lymph nodes as well as extranodal sites. Despite the characteristic histopathological features and distinctive immunophenotype, extranodal FDCS are often misdiagnosed initially as undifferentiated carcinoma, inflammatory pseudotumour, meningioma, metastatic malignant melanoma, ectopic thymoma, etc., because of its rarity and lack of awareness. Correct diagnosis of this tumour is imperative given its potential for recurrence and metastasis. We report a case of tonsillar FDCS in a 30-year-old lady who presented with slowly progressing throat pain and dysphagia for a duration of one year. Local examination showed an enlarged left tonsil with an ulceroproliferative growth. The right tonsil was normal. There was no regional lymphadenopathy. Histopathological examination of the tonsillectomy specimen showed a 2.2x1.5 cm infiltrative tumour composed of ovoid to spindle cells arranged in characteristic storiform, interlacing fascicular and diffuse patterns. The tumour cells were immunopositive for CD21, CD23, CD35, and S-100 protein and negative for cytokeratin. The Ki-67 antigen-labelling index (Ki-67 LI) was 6%. The EBV status was negative. It was classified as a low risk FDCS. The patient was lost to follow-up after 6 months.

A comparative evaluation of hyperbaric ropivacaine versus hyperbaric bupivacaine for elective surgery under spinal anesthesia.

BACKGROUND: Recently introduced ropivacaine is 40% less potent than bupivacaine. Ropivacaine made hyperbaric by the addition of dextrose is known to provide reliable spinal anesthesia (SA). This study was designed to compare the clinical efficacy of equal doses of hyperbaric 0.5% ropivacaine with 0.5% bupivacaine for SA. MATERIALS AND METHODS: Eighty American Society of Anesthesiologists grade I-II patients undergoing elective infraumbilical surgeries under SA were recruited and randomized to receive 3ml of hyperbaric ropivacaine 5mg/ml containing dextrose 83 mg/ml (by the addition of desired dose of 25% dextrose) in Group R or 3ml of hyperbaric bupivacaine 5mg/ml containing dextrose 80 mg/ml in Group B. Monitoring of vitals and observation for the block parameters were carried out. The data were presented as mean with a standard deviation and frequency with percentage. Statistical analysis was performed using InStat computer software with appropriate tests and P < 0.05 was considered to be significant. RESULTS: Ropivacaine produced a slower onset of sensory block (ropivacaine 4.5 min; bupivacaine 3.2 min; P < 0.05) and the mean total duration of sensory block was significantly lesser (ropivacaine155 min; bupivacaine 190.5 min; P < 0.05). Patients in the ropivacaine Group R had significantly more rapid recovery from the motor blockade (ropivacaine120 min; bupivacaine 190 min; P < 0.05) and passed urine sooner than the patients in bupivacaine Group B (ropivacaine 257 min; bupivacaine 358 min; P < 0.05). CONCLUSION: Ropivacaine 15 mg in dextrose 8.3% provides reliable SA of shorter duration than bupivacaine 15 mg in 8% dextrose.

Sodium Alginate Chitosan Crosslinked Hydrogel Amoxycillin Absorption Properties.

Wound healing refers to the replacement of destroyed or damaged tissue of a living organism by newly produced tissue, and the time taken is known as wound regeneration time. Wound care is a major challenging biomedical field due to the delayed healing process or delayed wound regeneration time. The factors responsible for delayed wound healing are poor oxygen flow, less exposure to moisture, diseases such as diabetes and cancer, etc., Wound dressings that are formulated from biopolymers such as chitosan, chitin, and cellulose have properties such as biocompatibility (compatible with living systems and does not cause any immunological rejection), biodegradable, nontoxic with minimal side effects, anti-microbial, anti-inflammatory properties. Chitosan is obtained from scales of fish and shrimp. It contains highly reactive amine groups and sodium alginate, which is a polysaccharide produced from seaweed and bacteria and is biocompatible with living systems and biodegradable polysaccharides. This study is based on the development of sodium alginate crosslinked hydrogel and testing the properties of hydrogel with amoxycillin drug and water release property of the drug.

Effect of Dextrose Cross-Linked Glutaraldehyde Hydrogel on Wound Healing Activity.

Dextrose cross-linked glutaraldehyde hydrogels are effective and promising drug delivery candidates. The addition of chitosan with dextrose resulted in the polymerization of material which resulted in the production of a gel-like structure that was highly viscous and had gelling properties. A swelling and absorption assay was conducted on the hydrogel. The dextrose cross-linked hydrogel has a higher absorption potential for distilled water followed by PBS and the least absorption was observed in the ethanol. Dextrose cross-linked hydrogel favors solubility in distilled water as compared to other solvents. The amoxicillin release by the dextrose cross-linked hydrogel was then tested. The result from drug release demonstrates that the dextrose cross-linked hydrogel released more than 55% of the amoxicillin in 2 hours and the remaining portion of the drug remaining. Therefore, it has a slow drug-release property, and it can be used for further wound-healing studies.

Doxycycline Drug Release Property of Glutaraldehyde Crosslinked Hydrogel.

Delayed wound healing is one of the most common problems associated with diabetic patients. There are several factors associated with delayed wound healing. It has been observed that if not cured the wound healing takes a long time. This is the reason that researchers are engaged in developing sustainable, biodegradable, biocompatible, and effective wound-healing dressings. However, it has been observed that the traditional wound-healing bandages have drawbacks such as allergies and less efficiency in the absorption of wound exudate. To fill the gap, hydrogels have been developed recently which have higher absorption capacity. In addition, they pose slow drug release properties. Therefore, the present study was conducted to prepare an effective and promising hydrogel that has high drug absorption and release properties.

Starch Glutaraldehyde Cross-Linked Hydrogel for Drug Release Properties.

In this study, we synthesized and characterized a novel starch glutaraldehyde cross-linked hydrogel for drug release. The hydrogel exhibited excellent properties such as absorption capacity and drug release. By optimizing the cross-linking reaction using varying concentrations of glutaraldehyde and reaction time, we obtained a hydrogel with a three-dimensional network structure, superior swelling properties, and mechanical strength. The results revealed doxycycline sustained and controlled drug release over a prolonged period, which could be adjusted by altering the cross-linking density of the hydrogel. Overall, the starch glutaraldehyde cross-linked hydrogel shows great promise as a drug delivery system with controlled release properties, applicable in pharmaceuticals and tissue engineering.

Polyethylene Glycol Cross-Linked Hydrogel for Drug Absorption Properties.

Three-dimensional polymeric networks called hydrogels have drawn a lot of interest in a variety of biomedical applications because of their distinctive qualities, like high water content and biocompatibility. Hydrogels can be strengthened mechanically and become more stable via cross-linking. In this study, we described the synthesis and characterization of a cross-linked hydrogel made of polyethylene glycol (PEG) capable of absorbing drug. The hydrogel was created by using a polymerization procedure to cross-link PEG chains. In order to allay this worry, we added particular functional groups to the hydrogel matrix that had a strong affinity for glutaraldehyde. These functional groups made it easier for excess glutaraldehyde to be absorbed and sequestered inside the hydrogel, lowering its cytotoxic potential. After incubation with the hydrogel, the residual glutaraldehyde concentration in solution was measured in order to assess the glutaraldehyde absorption potential.

Rare coexistence of spinal muscular atrophy with membranous nephropathy - A clinical conundrum with management dilemma.

ABSTRACT: A 48-year-old male presented with proximal muscle weakness of the shoulder with difficulty in lifting objects above the shoulder in July 2012. Electromyogram was suggestive of chronic motor axonal loss with a myogenic pattern, and a deltoid muscle biopsy revealed groups of atrophic muscle fibers and hypertrophic fibers with pan fascicular atrophy suggestive of adult-onset spinal muscular atrophy. He was managed conservatively and developed bilateral pedal edema in August 2022. He had nephrotic range proteinuria, and renal biopsy revealed capillary wall thickening of glomeruli with serum PLA2R antibody positivity suggestive of primary membranous nephropathy. He was managed with telmisartan for 6 months, and there was a reduction in proteinuria. In January 2023, he was given Injection Rituximab due to worsening proteinuria. He failed to have a clinical resolution. This case report describes the management dilemma in membranous nephropathy with SMA due to the risk of toxic myopathies associated with tacrolimus and steroids.

A Study on Pressure Ulcer: Influencing Factors and Diagnostic Techniques.

Pressure ulcer (PU) is one of the most common occurrences in bedridden subjects. Despite the standard of care, there is a huge challenge in monitoring immobile subjects in all the bodily pressure points. This increases the chance of onset of PU which in turn increases the expenditure for treating and managing the PU. Hence, we made a study on the biological and physiological factors that are responsible for the formation of PU and also on various techniques used for diagnosis. Thus, we have summarised the efficacy of various advanced diagnostic procedures with their limitations. Though there are advanced imaging techniques, risk assessment tools based on the visual inspection are widely followed in hospitals. Based on our observation, we here have identified three major areas; one being the development of mathematical modeling, the second is towards the development of non-invasive devices and finally to automate cot facility. We have also provided possible suggestions as to solutions that could be useful to researchers and for society. Thus, this review covers the present difficulty faced by bedridden subjects and respective care-takers along with the knowledge gap and a few suggestions as to future scope.

Metaheuristic Optimization-Driven Novel Deep Learning Approach for Brain Tumor Segmentation.

Brain tumor has the foremost distinguished etiology of high morality. Neoplasm, a categorization of brain tumors, is very operative in distinguishing and determining the tumor's exact location in the brain. Magnetic resonance imaging (MRI) is an efficient noninvasive technique for the anatomical examination of brain tumors. Growth tissues have a distinguishable look in MRI pictures in order that they are unit-wide used for brain tumor feature extraction. The existing research algorithms for brain tumors have some limitations such as different qualities, low sensitivity, and diagnosing the tumor at its stages. In this particular piece of research, an innovative method of optimization known as the procedure for lightning attachment algorithm (PLA) is used, and for the purpose of classification, a CNN model known as DenseNet-169 is applied. PLA was used in order to optimize the growth, and a network model known as the DenseNet-169 model was utilized in order to extract the various growth-optimization choices. First, the MR images of the brain were preprocessed to remove any outliers. Next, the Dense Net-169 CNN model was used to extract network choices from the MR images. In addition, it is used to execute the function of a classifier in order to identify the growth as either an aberrant growth or a traditional growth. In addition, the publicly benchmarked datasets that are widely utilized have validated the algorithmic rule that was granted. The planned system demonstrates the satisfactory accuracy in getting ready to on the dataset and outperforms many of the notable current techniques.

Face Mask in COVID-19 and Its Association With Dry Eye Disease: A Cross-Sectional Study.

AIM: To determine whether wearing a face mask for more than three to six hours/day leads to the new onset of symptoms or worsening of pre-existing dry eye disease (DED) in healthcare workers (HCWs) of our institute. METHODOLOGY: An observational cross-sectional study, where 114 HCWs using face masks regularly participated voluntarily in the study. A survey with a modified Ocular Surface Disease Index (OSDI) questionnaire was completed by participants. They were divided into groups based on their sex, age, how long they had been wearing face masks, and whether they had a history of DED. RESULTS: We found that for HCWs who had previously experienced DED and who were under the age of 40, wearing a face mask for more than three to six hours/day could contribute to or worsen symptoms of DED. Also, we observed that the N-95 mask has a higher chance of causing DED than surgical masks. CONCLUSION: Medical professionals need to be aware of any potential dry eye symptoms related to the prolonged use of a face mask. Additional consideration should be given to patients who already have DED. The possible concerns that incorrectly fitted facemasks may cause to the health of their ocular surface should be discussed with patients by ophthalmologists. Future research involving larger populations will shed light on the prevalence and scope of the mask-associated dry eye problem.

Everything real about unreal artificial intelligence in diabetic retinopathy and in ocular pathologies.

Artificial Intelligence is a multidisciplinary field with the aim of building platforms that can make machines act, perceive, reason intelligently and whose goal is to automate activities that presently require human intelligence. From the cornea to the retina, artificial intelligence (AI) is expected to help ophthalmologists diagnose and treat ocular diseases. In ophthalmology, computerized analytics are being viewed as efficient and more objective ways to interpret the series of images and come to a conclusion. AI can be used to diagnose and grade diabetic retinopathy, glaucoma, age-related macular degeneration, cataracts, IOL power calculation, retinopathy of prematurity and keratoconus. This review article intends to discuss various aspects of artificial intelligence in ophthalmology.

Rational design of a macrocyclic-based chemosensor for anions.

A macrocyclic-based fluorescence chemosensor has been designed and synthesized from the reaction of dansyl chloride and a hexaaminomacrocycle containing four secondary and two tertiary amines. The new chemosensor has been examined for its binding ability toward phosphate, sulfate, nitrate, iodide, bromide, chloride, and fluoride by fluorescence spectroscopy in DMSO. The results indicate that the compound binds each of the anions with a 1:1 stoichiometry, showing high affinity for the oxoanions, chloride and iodide with the binding constants up to four orders of magnitude. Ab initio calculations based on density functional theory (DFT) suggest that the ligand is deformed in order to encapsulate an anion, and each anion, except fluoride, is bonded to the macrocycle through two NH…X(-) and four CH…X(-) interactions.

Binding and selectivity aspects of an expanded azamacrocycle for anions.

An expanded azamacrocycle L, containing four secondary and two tertiary amines was synthesized, and its binding ability towards chloride, bromide, iodide, sulfate, nitrate and perchlorate were determined by (1)H NMR titrations in D(2)O at pH 1.7. The results suggest that the ligand is capable of forming a complex with each of the anions examined, showing the selectivity for sulfate in water. X-ray diffraction analysis of the perchlorate complex of L suggests that the ligand is tetraprotonated and is involved in interacting anions from both sides forming a ditopic complex with strong NH···O bonds. In the packing diagram, the macrocycles and external perchlorates are alternatively linked though hydrogen bonding to form a 1D chain.

A new hexaaminomacrocycle for ditopic binding of bromide.

A hexaaminomacrocycle L, containing four secondary and two tertiary amines has been synthesized and crystallized with hydrobromic acid. Structural analysis of the bromide complex suggests that the ligand in its tetrtaprotonated form, is involved in coordinating two bromides from both sides via hydrogen bonding interactions with N…Br(-) distance of 3,351 Å, forming a ditopic complex. The other two bromides are outside the cavity, and singly bonded to the macrocycle. The molecules are packed showing layer structures in which the internal bromides are locked between the layers of macrocycles. The bromide anions are coordinated alternatively by one and two hydrogen bonds with the protonated amines from the two adjacent macrocycles.

1,3-Phenyl-enediammonium dinitrate.

In the title compound, C(6)H(10)N(2) (2+)·2NO(3) (-), the dication lies on a crystallographic twofold rotation axis. The nitrate ions are linked to the dications though N-H⋯O hydrogen bonds, forming a three-dimensional network.

An systematic review of e-learning outcomes in undergraduate dental radiology curricula-levels of learning and implications for researchers and curriculum planners.

OBJECTIVES: To examine the outcomes of e-learning or blended learning interventions in undergraduate dental radiology curricula and analyze the nature of the knowledge levels addressed in learning interventions. METHODS: A systematic literature review was performed using a search strategy based on MeSH key words specific to the focus question and indexed in the MEDLINE database. The search again was supplemented by hand-searching of selected journals. Data were extracted relating to outcomes of knowledge and student perceptions. Analysis of the e-learning intervention was performed using a new framework to examine the level of knowledge undertaken: (1) remember/understand (2) analysis or evaluation or diagnosis and (3) performance ("knows how" or "shows how"). RESULTS: From the selected 17 papers, 11 were positive about student reported outcomes of the interventions, and 8 reported evidence that e-learning interventions enhanced learning. Out of the included studies, 8 used e-learning at the level of remember/understand, 4 at the level of analysis/evaluate/diagnosis, and 5 at the level of performance ("knows how," "shows how"). CONCLUSIONS: The learning objectives, e-learning intervention, outcome measures and reporting methods were diverse and not well reported. This makes comparison between studies and an understanding of how interventions contributed to learning impractical. Future studies need to define "knowledge" levels and performance tasks undertaken in the planning and execution of e-learning interventions and their assessment methods. Such a framework and approach will focus our understanding in what ways e-learning is effective and how it contributes to better evidence-based e-learning experiences.

Utility of tissue Doppler and strain echocardiography in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable cardiomyopathy characterized by the fibrofatty replacement of right ventricular (RV) myocardium leading to RV failure and arrhythmias. This study evaluated the potential utility of tissue Doppler echocardiography (TDE) and strain echocardiography (SE) to quantitatively assess RV function and their potential role in diagnosing ARVD. Images of 30 patients with ARVD (diagnosed by task force criteria) and 36 healthy controls were obtained. Peak systolic velocity, early diastolic velocity, displacement, strain rate, strain, outflow tract diameter, and fractional RV area change were measured in all subjects. Peak RV systolic velocity (6.4 +/- 2.2 vs 9 +/- 1.6 cm/s, p <0.0001), early diastolic velocity (-6.7 +/- 2.7 vs -9.4 +/- 2 cm/s, p <0.0001), displacement (13.7 +/- 5.8 vs 18.7 +/- 3.5 mm, p <0.0003), strain rate (-1 +/- 0.7 vs -2 +/- 1 s(-1), p = 0.002), and strain (-10 +/- 6% vs -28 +/- 11%, p = 0.001) were significantly lower in patients with ARVD compared with controls, respectively. Sensitivity and specificity, respectively, were 67% and 89% for systolic velocity, 77% and 71% for displacement, 73% and 87% for strain, 50% and 96% for strain rate, 53% and 93% for outflow tract diameter, and 47% and 83% for fractional area change. RV systolic velocity and displacement were significantly lower than in controls, even in the subset of patients with ARVD with apparently normal right ventricles by conventional echocardiography. Inter- and intraobserver agreement was high. In conclusion, TDE and SE enable the detection of ARVD via the quantification of RV function and may have potential clinical value in the assessment of patients with suspected ARVD. Peak RV systolic velocity <7.5 cm/s and peak RV strain <18% best identify patients with ARVD.