Proportion of Peripheral Arterial Disease in Patients with Chronic Kidney Disease.

Among the different complications of chronic kidney diseases, peripheral arterial disease is not uncommon. Though it is an indicator of widespread atherosclerosis, sometimes it is neglected in CKD patients. Our study was done to evaluate the frequency and pattern of PAD in chronic kidney disease patients admitted in a tertiary care hospital of Bangladesh. One hundred (100) admitted patients of CKD were taken by nonrandom purposive sampling considering inclusion and exclusion criteria. After clinical evaluation and Ankle brachial index (ABI) measurement 5 cc venous blood was collected and sent to Clinical Pathology and Biochemistry department of CMCH. Data was collected in a structured proforma and analyzed. Among the 100 patients, 2.0% patient belonged to stage 3, 28.0% were in stage 4 and remaining 70.0% were in stage 5. We found the proportion of PAD in CKD were 18.0%. Among 18 PAD patients, 66.67% were in stage 5, 22.22% in stage 4 and 11.11% in stage 3. Regarding right lower limb 12 patients had some PAD, 3 patients had moderate PAD, 2 patients had borderline and 1 patient had calcified PAD. For left lower limb, 10 patients had some PAD, 4 patients had moderate PAD, 4 patients had borderline PAD. The mean AB) of the PAD patients for right limb was 0.87 and for left limb 0.84. 50.0-55.0% patients were asymptomatic. Among the PAD patients 38.9% had DM, 72.2% had HTN, 33.3% had both DM and HTN, 44.4% had other vascular events, 55.6% were smokers, 33.3% had dyslipidemia and 22.2% had family history of PAD. Renal diseases seem to have a strong association with vascular disease and PAD is not uncommon.

IQGAP-2: A novel interacting partner for the Human Colonic Thiamin Pyrophosphate Transporter (hcTPPT).

The human colonic thiamin pyrophosphate transporter (hcTPPT) mediates the uptake of the microbiota-generated and phosphorylated form of vitamin B1 (i. e., thiamin pyrophosphate) in the large intestine. Expression of hcTPPT along the absorptive tract is restricted to the large intestine and the transporter is exclusively localized at the apical membrane domain of the polarized epithelial cells/colonocytes. Previous studies have characterized different physiological/pathophysiological aspects of the hcTPPT system, but nothing is currently known on whether the transporter has interacting partner(s) that affects its physiology/biology. We addressed this issue using a Y2H to screen a human colonic cDNA library, and have identified 3 putative interactors, namely IQGAP-2, SNX-6 and DMXL-1. Focusing on IQGAP-2 (whose expression in human colonocytes is the highest), we found (using fluorescent microscopy imaging and co-immunoprecipitation approaches) the putative interactor to co-localize with hcTPPT, and to directly interact with the transporter. Also, over-expressing IQGAP-2 in NCM460 cells and in human primary differentiated colonoid monolayers was found to lead to significant (P < 0.01) induction in TPP uptake, while it's knocking down (using gene-specific siRNAs) caused significant (P < 0.01 & < 0.05) decrease in uptake. Furthermore, over-expressing IQGAP-2 in NCM460 cells was found to lead to a significant enhancement in hcTPPT protein stability. Finally, we found the expression of IQGAP-2 to be markedly suppressed in conditions/factors that negatively impact colonic TPP uptake. These results identify the IQGAP-2 as an interacting partner with the hcTPPT in human colonocytes and show that this interaction has physiological and biological consequences.

Rapid and non-invasive diagnosis of hyperkalemia in patients with systolic myocardial failure using a model based on machine learning algorithms.

Background: Hyperkalemia is a potentially life-threatening electrolyte disturbance that if not diagnosed on time may lead to devastating conditions and sudden cardiac death. Blood sampling for potassium level checks is time-consuming and can delay the treatment of severe hyperkalemia on time. So, we propose a non-invasive method for correct and rapid hyperkalemia detection. Methods: The cardiac signal of patients referred to the Pediatrics Emergency room of Shahid Rejaee Hospital was measured by a 12-lead Philips electrocardiogram (ECG) device. Immediately, the blood samples of the patients were sent to the laboratory for potassium serum level determination. We defined 16 features for each cardiac signal at lead 2 and extracted them automatically using the algorithm developed. With the help of the principal component analysis (PCA) algorithm, the dimension reduction operation was performed. The algorithms of decision tree (DT), random forest (RF), logistic regression, and support vector machine (SVM) were used to classify serum potassium levels. Finally, we used the receiver operation characteristic (ROC) curve to display the results. Results: In the period of 5 months, 126 patients with a serum level above 4.5 (hyperkalemia) and 152 patients with a serum potassium level below 4.5 (normal potassium) were included in the study. Classification with the help of a RF algorithm has the best result. Accuracy, Precision, Recall, F1, and area under the curve (AUC) of this algorithm are 0.71, 0.87, 0.53, 0.66, and 0.69, respectively. Conclusions: A lead2-based RF classification model may help clinicians to rapidly detect severe dyskalemias as a non-invasive method and prevent life-threatening cardiac conditions due to hyperkalemia.

Bacterial lipopolysaccharide inhibits free thiamin uptake along the intestinal tract via interference with membrane expression of thiamin transporters 1 and 2.

This study examined the effect of exposure of small and large intestinal epithelial cells to the bacterial lipopolysaccharide (LPS) on uptake of free form of vitamin B1, i.e., thiamin. The intestinal tract encounters two sources of thiamin: diet and the gut microbiota. Absorption of thiamin in both the small and large intestine occurs via a carrier-mediated process that involves thiamin transporters 1 and 2 (THTR-1 and -2). Complementary in vitro (human duodenal epithelial HuTu-80 cells and human colonic epithelial NCM460 cells), in vivo (mice), and ex vivo (human primary differentiated enteroid and colonoid monolayers) models were used. The results showed that exposure to LPS causes a significant inhibition in carrier-mediated [3H]-thiamin uptake by small and large intestinal epithelia, with no change in the levels of expression of THTR-1 and -2 mRNAs and their total cellular proteins. However, a significant decrease in the fractions of the THTR-1 and -2 proteins that are expressed at the cell membranes of these epithelial cells was observed. These effects of LPS appeared to involve a protein kinase A (PKA) signaling pathway as activating this pathway caused a reversal in the inhibition of thiamin uptake and level of expression of its transporters at the cell membrane. These findings demonstrate that exposure of gut epithelia to LPS (a situation that occurs under different pathological conditions) leads to inhibition in thiamin uptake due to a decrease in level of expression of its transporters at the cell membrane that is likely mediated via a PKA signaling pathway. NEW & NOTEWORTHY This study shows that the exposure of gut epithelial cells to bacterial LPS negatively impact the uptake process of the free form of vitamin B1 (i.e., thiamin). This appears to be mediated via suppression in the level of thiamin transporters 1 and 2 (THTR-1 and -2) expression at the cell membrane and involves a protein kinase A (PKA) signaling pathway.

Species-Specific Root Distribution and Leaf Iso/Anisohydric Tendencies Shape Transpiration Patterns Across Heterogeneous Karst Habitats.

The driving forces of transpiration are not only atmospheric evaporation but also root zone water supply and stomatal regulation among species. However, the biophysiological drivers of transpiration remain incompletely understood in heterogeneous karst habitats. This study investigated the commonly coexisting tree species Mallotus philippensis and Celtis biondii in two typical karst habitats: rock-dominated (RD) habitat and control soil-dominated (SD) habitat. Over 2 years, soil moisture, transpiration, root distribution, and leaf water potential were measured. The results showed that soil moisture in the RD habitat was significantly lower than in the SD habitat. Transpiration patterns also differed between habitats, with species-specific distinctions driven by biophysiological traits. M. philippensis showed small hydroscape areas and its root system mainly distributed in the soil zone in both habitats. The isohydric behaviour and lower root density in the RD habitat drove M. philippensis to reduce transpiration in response to soil water deficiency. Conversely, C. biondii had large hydroscape areas and roots capable of penetrating bedrock. It transpired higher relying on ample accessible water through anisohydric behaviour and having a more robust root system both in soil and bedrock zones in the RD habitat. Our study highlights the critical role of root water accessibility and leaf iso/anisohydric tendencies in driving transpiration.

Novel candidates synthesis of indenopyrazole, indenoazine and indenothiophene, with anticancer and in silico studies.

Aim: The indandione nucleus, is one of the most amazing nuclei in medicinal chemistry, is used to design new derivatives.Methods & materials: Novel indandione derivatives are prepared with different electrophilic and nucleophilic reagents to yield 3, 4, 8, 11, 14, 16, 19, 20, 21, 22 and 23. Compounds 8, 11, 16, 20 and 23 are investigated against OVCAR-3 and HeLa, using LLC-MK2 and cis-Pt as references. in silico and spectral studies were analyzed for the selected compounds.Results: Compounds 20 and 23 at 100 ns were the most potent compounds, so molecular dynamics studies were performed.Conclusion: Compound 23 was the most active toward the HeLa cervical cell line, and compound 20 was the most active toward the Ovcar-3 cell line.

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Redundancy in microbiota-mediated suppression of the soybean cyst nematode.

BACKGROUND: Soybean cyst nematodes (SCN) as animal parasites of plants are not usually interested in killing the host but are rather focused on completing their life cycle to increase population, resulting in substantial yield losses. Remarkably, some agricultural soils after long-term crop monoculture show a significant decline in SCN densities and suppress disease in a sustainable and viable manner. However, relatively little is known about the microbes and mechanisms operating against SCN in such disease-suppressive soils. RESULTS: Greenhouse experiments showed that suppressive soils (S) collected from two provinces of China and transplantation soils (CS, created by mixing 10% S with 90% conducive soils) suppressed SCN. However, SCN suppressiveness was partially lost or completely abolished when S soils were treated with heat (80 °C) and formalin. Bacterial community analysis revealed that the specific suppression in S and CS was mainly associated with the bacterial phylum Bacteroidetes, specifically due to the enrichment of Chitinophaga spp. and Dyadobacter sp., in the cysts. SCN cysts colonized by Chitinophaga spp. showed dramatically reduced egg hatching, with unrecognizable internal body organization of juveniles inside the eggshell due to chitinase activity. Whereas, Dyadobacter sp. cells attached to the surface coat of J2s increased soybean resistance against SCN by triggering the expression of defence-associated genes. The disease-suppressive potential of these bacteria was validated by inoculating them into conducive soil. The Dyadobacter strain alone or in combination with Chitinophaga strains significantly decreased egg densities after one growing cycle of soybeans. In contrast, Chitinophaga strains alone required more than one growing cycle to significantly reduce SCN egg hatching and population density. CONCLUSION: This study revealed how soybean monoculture for decades induced microbiota homeostasis, leading to the formation of SCN-suppressive soil. The high relative abundance of antagonistic bacteria in the cyst suppressed the SCN population both directly and indirectly. Because uncontrolled proliferation will likely lead to quick demise due to host population collapse, obligate parasites like SCN may have evolved to modulate virulence/proliferation to balance these conflicting needs. Video Abstract.

Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology.

Humans and mammals obtain vitamin B1 from dietary and gut microbiota sources. A considerable amount of the microbiota-generated vitamin exists in the form of thiamine pyrophosphate (TPP), and colonocytes are capable of absorbing TPP via a specific carrier-mediated process that involves the colonic TPP transporter (cTPPT encoded by SLC44A4). Little is known about the relative contribution of the SLC44A4 transporter toward total colonic carrier-mediated TPP uptake and its role in colon physiology. To address these issues, we generated an Slc44a4 knockout (KO) mouse model (by Cre-Lox recombination) and found a near-complete inhibition in colonic carrier-mediated [3H]TPP uptake in the Slc44a4 KO compared with wild-type (WT) littermates. We also observed a significant reduction in KO mice's body weight and a shortening of their colon compared with WT. Using RNAseq and Ingenuity pathway analysis (IPA) approaches, we found that knocking out the colonic Slc44a4 led to changes in the level of expression of many genes, including upregulation in those associated with intestinal inflammation and colitis. Finally, we found that the Slc44a4 KO mice were more susceptible to the effect of the colitogenic dextran sodium sulfate (DSS) compared with WT animals, a finding that lends support to the recent prediction by multiple genome-wide association studies (GWAS) that SLC44A4 is a possible colitis susceptibility gene. In summary, the results of these investigations show that Slc44a4 is the predominant or only transporter involved in the colonic uptake of TPP, that the transporter is important for colon physiology, and that its deletion increases susceptibility to inflammation.NEW & NOTEWORTHY This study shows that Slc44a4 is the predominant or only transport system involved in the uptake of the gut microbiota-generated thiamine pyrophosphate (TPP) in the colon and that its deletion affects colon physiology and increases its susceptibility to inflammation.

Genome sequencing enables diagnosis and treatment of SLC5A6 neuropathy.

The sodium-dependent multivitamin transporter encoded by SLC5A6 is responsible for uptake of biotin, pantothenic acid, and α-lipoic acid. Thirteen individuals from eight families are reported with pathogenic biallelic SLC5A6 variants. Phenotype ranges from multisystem metabolic disorder to childhood-onset peripheral motor neuropathy. We report three additional affected individuals with biallelic SLC5A6 variants. In Family A, a male proband (AII:1) presenting in early childhood with gross motor regression, motor axonal neuropathy, recurrent cytopenia and infections, and failure to thrive was diagnosed at 12 years of age via genome sequencing (GS) with a paternal NM_021095.4:c.393+2T>C variant and a maternal c.1285A>G p.(Ser429Gly) variant. An uncle with recurrent cytopenia and peripheral neuropathy was subsequently found to have the same genotype. We also report an unrelated female with peripheral neuropathy homozygous for the c.1285A>G p.(Ser429Gly) recurrent variant identified in seven reported cases, including this study. RT-PCR studies on blood mRNA from AII:1 showed c.393+2T>C caused mis-splicing with all canonically spliced transcripts in AII:1 containing the c.1285A>G variant. SLC5A6 mRNA expression in AII:1 fibroblasts was ~50% of control levels, indicative of nonsense-mediated decay of mis-spliced transcripts. Biotin uptake studies on AII:1 fibroblasts, expressing the p.(Ser429Gly) variant, showed an ~90% reduction in uptake compared to controls. Targeted treatment of AII:1 with biotin, pantothenic acid, and lipoic acid resulted in clinical improvement. Health Economic analyses showed implementation of GS as an early investigation could have saved $ AUD 105,988 and shortened diagnostic odyssey and initiation of treatment by up to 7 years.

The outcome of 12-week corticosteroid therapy in COVID-19-related diffuse interstitial lung abnormalities.

INTRODUCTION: The efficacy of long-course corticosteroid therapy in treating COVID-19-related diffuse interstitial lung abnormalities (DILA) needs to be better understood. We aimed to investigate the benefits of 12-week corticosteroid treatment in COVID-19-related DILA by evaluating computed tomography (CT) lung severity scores. MATERIALS AND METHODS: This retrospective, single-centre observational study included patients aged 18 years or older admitted with moderate to severe COVID-19 pneumonia who received 12 weeks of oral prednisolone between January 2021 and December 2021. We recorded clinical parameters, baseline CT scores and post-treatment, modified Medical Research Council (mMRC) dyspnoea scale and pulmonary function tests. RESULTS: A total of 330 patients were analysed. The mean (standard deviation, SD) age was 54.6 (14.2) years, and 43% were females. Three-point nine per cent (3.9%) require noninvasive ventilation (NIV), while 14.6% require mechanical ventilation (MV). On follow-up at 12 weeks, the CT patterns showed improvement in ground-glass opacities, perilobular density and consolidation. There was an improvement in the mean (SD) CT score before and after prednisolone therapy, with values of 17.3 (5.3) and 8.6 (5.5), respectively (p<0.001). The median mMRC was 1 (IQR 0-1), and 98.8% had a radiological response. The common side effects of prednisolone therapy were weight gain (13.9%), hyperglycaemia (1.8%) and cushingoid habitus (0.6%). CONCLUSION: A 12-week treatment with prednisolone showed significant improvement in CT scores with minimal residual dyspnoea and was relatively safe. Longer duration of steroids may be beneficial in moderate to severe COVID-19- related DILA.

NTRK3-Rearranged Prostatic Acinar Adenocarcinoma: Report of a Patient and Review of the Literature.

Molecular investigations have led to increased therapeutic options for prostatic adenocarcinoma. A single case report of a PRPSAP1::NTRK3 gene fusion occurring in prostate cancer was previously reported. A review of the literature revealed that NTRK gene rearrangements are exceedingly rare molecular events in prostate cancer. NTRK gene fusions can be oncogenic drivers or develop as resistance mechanisms. The tumor-agnostic approvals of TRK inhibitors by the FDA provide additional rationale for molecular investigations of aggressive prostatic adenocarcinomas. This may prove to be an additional therapeutic option for patients with aggressive prostatic carcinomas refractory to initial therapy. We report a case of an aggressive castrate-resistant prostatic adenocarcinoma with a BMP6::NTRK3 gene fusion.

Insights Into MRI Neuroimaging Patterns of COVID-19 in Children: A Retrospective Comprehensive Analysis.

RATIONALE AND OBJECTIVES: Neurological complications associated with coronavirus disease (COVID-19) have been reported in children; however, data on neuroimaging findings remain limited. This study aimed to comprehensively examine neuroimaging patterns of COVID-19 in children and their relationship with clinical outcomes. MATERIALS AND METHODS: This retrospective cross-sectional study involved reviewing the medical records and MRI scans of 95 children who developed new neurological symptoms within 2-4 weeks of clinical and laboratory confirmation of COVID-19. Patients were categorized into four groups based on guidelines approved by the Centers for Disease Control and Prevention (CDC). Initial brain/spinal MRI was performed. Images were reviewed by three blinded radiologists, and the findings were analyzed and categorized based on the observed patterns in the brain and spinal cord. Follow-up MRI was performed and analyzed to track lesion progression. RESULTS: Encephalopathy was the most common neurological symptom (50.5%). The most common initial MRI involvement patterns were non-confluent multifocal hyperintense white matter (WM) lesions (36.8%) and ischemia (18.9%). Most patients who underwent follow-up MRI (n = 56) showed complete resolution (69.9%); however, some patients developed encephalomalacia and myelomalacia (23.2% and 7.1%, respectively). Non-confluent hyperintense WM lesions were associated with good outcomes (45.9%, P = 0.014), whereas ischemia and hemorrhage were associated with poor outcomes (44.1%, P < 0.001). CONCLUSION: This study revealed diverse neuroimaging patterns in pediatric COVID-19 patients. Non-confluent WM lesions were associated with good outcomes, whereas ischemia and hemorrhage were associated with poorer prognoses. Understanding these patterns is crucial for their early detection, accurate diagnosis, and appropriate management.

A DFT approach to correlate the physical characteristics of novel chalcopyrites ASbN2(A = Li, Na) for green technology.

Semiconductor chalcopyrite compounds have been a subject of research interest due to their diverse range of physical properties that have captured the attention of scientists. In this ongoing research, we have examined the physical characteristics of LiSbN2 and NaSbN2 chalcopyrites using DFT. The modified Becke-Johnson (mBJ) potential is utilized for the computation of electronic structures. The stability is attained with negative formation energies and optimization curves. A bandgap of 2.60 eV in LiSbN2 and 3.15 eV in NaSbN2 has been achieved, which is further endorsed by the density of states. An in-depth analysis of the optical properties unveils the potential utility of LiSbN2 and NaSbN2 in various photovoltaic devices, attributed to its pronounced absorption in the UV spectrum. The transport characteristics are also assessed through various transport characteristics. The large electrical conductivity and ZT values for both chalcopyrite compounds are attained. Due to their remarkable capability to convert heat into electricity, these materials display potential for use in thermoelectric devices.

Abbreviated breast magnetic resonance imaging (MRI) or digital breast tomosynthesis for breast cancer detection in dense breasts? A retrospective preliminary study with comparable results.

AIM: To compare the diagnostic performance of abbreviated breast magnetic resonance (AB-MR) imaging (MRI) and digital breast tomosynthesis (DBT) for breast cancer detection in Malaysian women with dense breasts, using histopathology as the reference standard. MATERIALS AND METHODS: This was a single-centre cross-sectional study of 115 women with American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BIRADS) breast density C and D on DBT with breast lesions who underwent AB-MR from June 2018 to December 2021. AB-MR was performed on a 3 T MRI system with an imaging protocol consisting of three sequences: axial T1 fat-saturated unenhanced; axial first contrast-enhanced; and subtracted first contrast-enhanced with maximum intensity projection (MIP). DBT and AB-MR images were evaluated by two radiologists blinded to the histopathology and patient outcomes. Diagnostic accuracy (sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV]) was assessed. RESULT: Of the 115 women, the mean age was 50.6 years. There were 48 (41.7%) Malay, 54 (47%) Chinese, and 12 (10.4%) Indian women. The majority (n=87, 75.7%) were from the diagnostic population. Sixty-one (53.1%) were premenopausal and 54 (46.9%) postmenopausal. Seventy-eight (72.4%) had an increased risk of developing breast cancer. Ninety-one (79.1%) women had density C and 24 (20.9%) had density D. There were 164 histopathology-proven lesions; 69 (42.1%) were malignant and 95 (57.9%) were benign. There were 62.8% (n=103/164) lesions detected at DBT. All the malignant lesions 100% (n=69) and 35.7% (n=34) of benign lesions were detected. Of the 61 lesions that were not detected, 46 (75.4%) were in density C, and 15 (24.6%) were in density D. The sensitivity, specificity, PPV, and NPV for DBT were 98.5%, 34.6%, 66.3%, and 94.7%, respectively. There were 65.2% (n=107/164) lesions detected on AB-MR, with 98.6% (n=68) malignant and 41.1% (39) benign lesions detected. The sensitivity, specificity, PPV, and NPV for AB-MR were 98.5%, 43.9%, 67.2%, and 96.2%, respectively. One malignant lesion (0.6%), which was a low-grade ductal carcinoma in-situ (DCIS), was missed on AB-MR. CONCLUSION: The present findings suggest that both DBT and AB-MR have comparable effectiveness as an imaging method for detecting breast cancer and have high NPV for low-risk lesions in women with dense breasts.

The prognostic value of bone marrow retention index and bone marrow-to-liver ratio of baseline 18F-FDG PET/CT in diffuse large B-cell lymphoma.

OBJECTIVE: To determine prognostic value of bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) measured on baseline dual-phase 18F-FDG PET/CT in a series of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) treated homogeneously with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. PATIENTS AND METHODS: This prospective study enrolled 135 patients with newly diagnosed DLBCL. All patients underwent dual-phase 18F-FDG PET/CT. The following PET parameters were calculated for both tumor and bone marrow: maximum standardized uptake value (SUVmax) at both time points (SUVmax early and SUVmax delayed), SUVmax increment (SUVinc), RI, and BLR. Patients were treated with R-CHOP regimen and response at end of treatment was assessed. RESULTS: The final analysis included 98 patients with complete remission. At a median follow-up of 22 months, 57 patients showed no relapse, 74 survived, and 24 died. The 2-year relapse-free survival (RFS) values for patients with higher and lower RI-bm were 20% and 65.1%, respectively (p < 0.001), and for patients with higher and lower BLR were 30.2% and 69.6%, respectively (p < 0.001). The 2-year overall survival (OS) values for patients with higher and lower RI-bm were 60% and 76.3%, respectively (p = 0.023), and for patients with higher and lower BLR were 57.3% and 78.6%, respectively (p = 0.035). Univariate analysis revealed that RI-bm and BLR were independent significant prognostic factors for both RFS and OS (hazard ratio [HR] = 4.02, p < 0.001, and HR = 3.23, p < 0.001, respectively) and (HR = 2.83, p = 0.030 and HR = 2.38, p = 0.041, respectively). CONCLUSION: Baseline RI-bm and BLR were strong independent prognostic factors in DLBCL patients. CLINICAL RELEVANCE STATEMENT: Bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) could represent suitable and noninvasive positron emission tomography/computed tomography (PET/CT) parameters for predicting pretreatment risk in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. KEY POINTS: • Bone marrow retention index (RI-bm) and bone marrow-to-liver ratio (BLR) are powerful prognostic variables in diffuse large B-cell lymphoma (DLBCL) patients. • High BLR and RI-bm are significantly associated with poor overall survival (OS) and relapse-free survival (RFS). • RI-bm and BLR represent suitable and noninvasive risk indicators in DLBCL patients.

MRI-Based Classification for Tibial Spine Fracture: Detection Efficacy, Classification Accuracy, and Reliability.

RATIONALE AND OBJECTIVES: Recently, a new MRI-based classification for evaluating tibial spine fractures (TSFs) was developed to aid in treating these injuries. Our objective was to assess the detection efficacy, classification accuracy, and reliability of this classification in detecting and grading TSFs, as well as its impact on treatment strategy, compared to the Meyers and McKeever (MM) classification. MATERIALS AND METHODS: A retrospective study included 68 patients with arthroscopically confirmed TSFs. All patients had plain radiography and conventional MRI of the affected knee before arthroscopy. Three experienced radiologists independently reviewed all plain radiographs and MRI data and graded each patient according to MM and MRI-based classifications. The detection efficacy, classification accuracy, and inter-rater agreement of both classifications were evaluated and compared, using arthroscopic findings as the gold standard. RESULTS: The final analysis included 68 affected knees. Compared to the MM classification, the MRI-based classification produced 22.0% upgrade of TSFs and 11.8% downgrade of TSFs. According to the reviewers, the fracture classification accuracy of the MRI-based classification (91.2-95.6%) was significantly higher than that of the MM classification (73.5-76.5%, p = 0.002-0.01). The fracture detection rate of MRI-based classification (94.1-98.5%) was non-significantly higher than that of the MM classification (83.8-89.7%, p = 0.07-0.4). The soft tissue injury detection accuracy for MRI-based classification was 91.2-94.1%. The inter-rater reliability for grading TSFs was substantial for both the MM classification (κ = 0.69) and MRI-based classification (κ = 0.79). CONCLUSION: MRI-based classification demonstrates greater accuracy and reliability compared to MM classification for detecting and grading TSFs and associated soft tissue injuries.

Identification and Pathogenicity of Fusarium Species Associated with Young Vine Decline in California.

Grapevine trunk diseases are caused by a broad diversity of fungal taxa that have serious impacts on the worldwide viticulture industry due to significant reductions in vineyards yield and lifespan. Field surveys carried out from 2018 to 2022 in California nurseries and young vineyards revealed a high incidence of Fusarium. Since Fusarium species are important pathogens of other perennial crops, the present study aimed to identify and determine the pathogenicity of the Fusarium species on grapevines. Morphology of the fungal colonies coupled with multilocus phylogenetic analyses using nucleotide sequences of the translation elongation factor 1-alpha (tef1) and the RNA polymerase II second largest subunit (rpb2) genes revealed the occurrence of 10 species clustering in six species complexes, namely F. fujikuroi (FFSC), F. oxysporum (FOSC), F. solani (FSSC), F. sambucinum (FSAMSC), F. incarnatum-equiseti (FIESC), and F. tricinctum (FTSC) species complexes. The species F. annulatum (FFSC) was the most prevalent in samples from both symptomatic young vineyards (73.5% incidence) and nursery propagation material (62.5% incidence). Pathogenicity of the 10 most frequent species was confirmed by fulfilling Koch's postulates on living woody tissue of 1103 Paulsen rootstocks. Our results suggest that Fusarium spp. are involved in the development of young vine decline, probably as opportunistic pathogens when grapevines are under stress conditions.

Bone marrow-derived mesenchymal stem cells abate CCl4-induced lung damage via their modulatory effects on inflammation, oxidative stress and apoptosis.

OBJECTIVE: The aim of this study was to assess and compare the therapeutic effects of allogenic and xenogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) on a rat model for treating experimental lung inflammation, oxidative stress, and apoptosis. MATERIALS AND METHODS: Male Wistar rats were randomly divided into four groups. Group 1 received an intraperitoneal injection of olive oil vehicle (2 mL/kg body weight) for 8 weeks. Group 2 received an intraperitoneal injection of carbon tetrachloride (CCl4) (0.5 mL/kg body weight, twice/week) dissolved in olive oil for 8 weeks. Groups 3 and 4 received the CCl4 similar to group 2, followed by the intravenous injection of rat and mouse BM-MSCs (1 × 106 cells/rat twice/week into a lateral tail vein), respectively, for 4 weeks. Subsequently, the rats were sacrificed, and lung tissues were excised for molecular, histological, and ultrastructural investigations. RESULTS: Fibrosis, interstitial bleeding, dilatation and congestion of blood vessels, intra-alveolar edema, damaged alveoli, scattered mononuclear leucocytic infiltrates, and an increased number of apoptotic cells and apoptotic remnants were observed in the lungs of rats exposed to CCl4; the treatment with rat and mouse BM-MSCs attenuated these changes. The effects of CCl4 on the increase in collagen fibers in the lungs and the expression levels of cyclooxygenase-2, tumor necrosis factor-α, and apoptotic protein p53 were considerably reduced following treatment with the BM-MSCs. The higher levels of lipid peroxidation, the lower-level glutathione content, and the activities of superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase in CCl4-injected rats were significantly improved by treatments with rat and mouse BM-MSCs. CONCLUSIONS: These findings indicate that mouse and rat BM-MSCs, which were more potent, can protect against CCl4-induced lung damage and fibrosis by reducing inflammation, apoptosis, and oxidative stress and boosting the antioxidant defense system.

Paradigm shift towards emergency cholecystectomy: one site experience of the Chole-QuiC process.

INTRODUCTION: Substantial evidence exists for the superiority of emergency over delayed cholecystectomy for gallstone disease during primary admission. Despite this, emergency surgery rates in the UK remain low compared with other developed countries, with great variation in care across the nation. We aimed to describe the local paradigm shift towards emergency surgery and investigate outcomes. METHODS: This is a prospective observational study examining patients enrolled onto an emergency cholecystectomy pathway, following the hospital's subscription to the Royal College of Surgeons of England's Cholecystectomy Quality Improvement Collaborative (Chole-QuIC), between 1 December 2021 and 31 January 2023. Multivariate logistical regression models were used to identify patient and hospital factors associated with postoperative outcomes. RESULTS: Of the 307 suitable acute admissions, 261 (85%) had an emergency cholecystectomy, compared with 5% preceding the Chole-QuIC interventions. Waiting time dropped from 67 to 5 days. A total of 208 (79.7%) patients were primary presentations, 92 (35.2%) were classed Tokyo grade 2 and 142 (54.4%) were obese. A total of 23 (8.8%) patients underwent preoperative endoscopic retrograde cholangiopancreatography, and 26 (10%) patients had a subtotal cholecystectomy. Favourable outcomes (Clavien Dindo ≥3) were observed in first presentations (odds ratio (OR) 0.35; p=0.042) and for operation times within 7 days (OR 0.32; p=0.037), with worse outcomes in BMI ≥35 (OR 3.32; p=0.005) and operation time >7 days (OR 3.11; p=0.037). CONCLUSION: A paradigm shift towards emergency cholecystectomy benefits both the patient and the service. Positive outcomes are apparent for early operation in patients presenting for the first time and recurrent attendees, with early operation (<7 days) providing the most favourable outcome in a select patient group.