Idiopathic multicentric Castleman disease with marrow fibrosis and extramedullary hematopoiesis.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is a rare inflammatory disorder mediated by excessive proinflammatory cytokine signaling, most notably by interleukin 6 (IL-6). IL-6-induced extramedullary hematopoiesis (EMH) has been reported in murine models of iMCD. Herein we present four cases of iMCD with EMH in humans. CASE SERIES: The index case is a 24-year-old white woman who presented with pancytopenia, hepatosplenomegaly, and diffuse lymphadenopathy (LAD) with EMH in core lymph node biopsies. We then searched ACCELERATE, a Castleman disease (CD) natural history registry, and identified three additional CD cases with EMH reported in biopsies: A 23-year-old Asian man with fatigue, edema, LAD, and splenomegaly; a 20-year-old white man with fever, dyspnea, LAD, and hepatosplenomegaly; and a 50-year-old white man with constitutional symptoms, LAD, and myelodysplastic syndrome in bone marrow with a KRAS mutation. RESULTS: All four patients presented with thrombocytopenia and fever and/or markedly elevated C-reactive protein. Patient 1 had iMCD-NOS (not otherwise specified) with severe thrombocytopenia, reticulin fibrosis in bone marrow, small volume LAD and organomegaly but no anasarca. The other three patients had iMCD-TAFRO (thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly). Two had mixed CD and two had hypervascular CD in lymph nodes. All four had bone marrow hypercellularity and megakaryocyte hyperplasia and two had reticulin fibrosis. CONCLUSIONS: This case series demonstrates that EMH can be seen in CD, particularly in iMCD-TAFRO. Given the similarity of this finding to previous murine models of IL-6-induced marrow and lymph node changes we hypothesize that this is an IL-6-mediated phenomenon.

Developmental defects of enamel in childhood cancer survivors: A systematic review and meta-analysis.

AIM: The present systematic review and meta-analysis (Prospero registration number: CRD42023472016) aims to assess the prevalence of developmental defects of enamel (DDEs), qualitatively and/or quantitatively, in childhood cancer survivors (CCS) and evaluate, when possible, these data in comparison with those found in healthy children. METHODS: Three electronic databases (PubMed, Embase, Scopus) were searched from January 2003 to January 2024 for studies reporting on DDEs in children with a mean age not exceeding 16 years at the time of the study who underwent antineoplastic therapy. The ROBINS-I and the Joanna Briggs Institute (JBI) tools were used to assess the risk of bias. Included studies with comparable outcomes underwent random effects models meta-analysis using Stata®18. CONCLUSION: CCS showed a higher prevalence of DDEs, both qualitative and quantitative, compared to healthy children. The meta- analysis showed higher odds of developing qualitative defects over quantitative defects in CCS. Conclusions regarding the association between the type of therapy administered, age of therapy initiation, and prevalence of DDEs could not be drawn due to insufficient data. A lack of a standardized method of detecting enamel defects posed a challenge in the qualitative and quantitative analysis.

Immunohistochemical expression of vimentin, E-cadherin, and CD45 in natural cases of canine cutaneous round tumors.

Round cell tumors are common cutaneous lesions in dogs, with increased occurrence percentages among different skin tumors. This study aimed to investigate the frequency as well as gross and pathological characteristics of round cell tumors in natural cases of tumorous dogs in relation to breed, sex, and age. Moreover, it aimed to evaluate the immunohistochemical expression of a panel of immunohistochemical stains, including vimentin, E-cadherin, and cluster of differentiation (CD45) as an adjunct technique for the differential diagnosis of cutaneous round cell neoplasm. Data were collected from 64 dogs of both sexes (36 females and 28 males), various breeds, and different ages (8 months to 7 years). The histopathological nature of neoplastic growth was reported, and neoplasm prevalence was classified using age, sex, breed, and site on the body. We observed 48 cases of transmissible venereal tumors, 12 cutaneous histiocytomas, and 4 histiocytic sarcoma. Immunohistochemical characterization revealed an intense positive immunoreactivity for vimentin in transmissible venereal tumor cells and moderate positive immunoreactivity for E-cadherin and CD45 in cutaneous histiocytoma and histiocytic sarcoma cells. In conclusion, the canine transmissible venereal tumor was the most frequent form of round cell tumor; thus, a definitive cutaneous neoplasm diagnosis should be based on histopathological morphology and immunohistochemical findings.

Rehabilitation of patients with peripheral arterial disease.

Vascular rehabilitation is an essential and effective treatment of peripheral arterial obstructive disease (PAOD). It is recommended in the first line by the European and American scientific societies. The rehabilitation to the walk remains the basic treatment of the arteriopathy of the lower limbs. Different walking protocols can be proposed. For similar effectiveness, vascular rehabilitation consists of an outpatient or specialized institution management program based on a comprehensive approach involving all or many of the following techniques: relaxation, active analytical exercises, gait rehabilitation, exercise re-entry, physical activities adapted to the patient's daily life and illness, respiratory physiotherapy, therapeutic education of the patient, smoking cessation aid. Vascular rehabilitation of arteritis requires a variety of skills but still faces a clear lack of suitable structures; it remains poorly prescribed and poorly known by usual prescribers (general practitioner, vascular surgeon).

Synthesis, anticancer activity and molecular docking of new triazolo[4,5-d]pyrimidines based thienopyrimidine system and their derived N-glycosides and thioglycosides.

A series of new substituted triazolo[4,5-d]pyrimidine derivatives linked to thienopyrimidine ring system were prepared as a hybrid heterocyclic systems, as possible nucleobases analogs, starting from the key carboxamide derivative 2 and its azide precursor via heterocyclization reactions and their structures were characterized. Glycosylation of the prepared triazolopyrimidine derivatives was performed and afforded, regioselctively, the corresponding thienopyrimidine-triazolopyrimidine hybrid N1-glycosides and their thioglycoside analogues in good yields. The synthesized glycosyl heterocycles were studied for their cytotoxic activity against HepG-2 and MCF-7 human cancer cells and significant results were obtained. Compounds 7a, 8 b, 9 b, 9a and 7 b demonstrated promising activities comparable to the activity of the doxorubicin for (HepG-2) cell line. Furthermore, a number of the afforded triazolopyrimidine glycosides were found potent against cancer cells (MCF-7). Furthermore, docking simulation the promising thienopyrimidine analogues 7-13 was done against EGFR kinase to provide a binding model that could serve in discovery of further anticancer agents.

Click chemistry based synthesis, cytotoxic activity and molecular docking of novel triazole-thienopyrimidine hybrid glycosides targeting EGFR.

In the current study, new thienopyrimidine conjugates bearing 1,2,3-triazole core and different sugar moieties have been designed and synthesized by Cu(I)-catalysed click dipolar cycloaddition. The cytotoxic activity of the synthesised conjugates 2, 5, 7, and 13-18 was studied against HCT-116 and MCF-7 cell lines by the MTT assay. The triazole glycosides 16 and 18 provided significant cytotoxic activities against HCT-116 cell lines comparable to that of doxorubicin and other studied compounds. The cytotoxic behaviour against MCF-7 exhibited that all the investigated compounds were more potent than doxorubicin. Moreover, all screened targets were evaluated against mutant EGFR kinase type L858R and the results revealed that the acetylated 1,2,3-triazole glycosides 13-18 exhibited excellent EGFR inhibitory activity in comparison with gefitinib. Furthermore, molecular modelling studies were performed to investigate the binding affinity of the most active compounds to EGFR enzyme.

Surgical and functional outcomes of two types of transcutaneous bone conduction implants.

OBJECTIVE: This study aimed to evaluate surgical and functional outcomes, in a tertiary referral centre, of two different types of semi-implantable transcutaneous bone conduction devices. METHOD: This study involved prospective data collection and review of patients implanted between November 2014 and December 2016. Glasgow Hearing Aid Inventory (Glasgow Hearing Aid Benefit Profile or Glasgow Hearing Aid Difference Profile) and Client Oriented Scale of Improvement were completed where appropriate. Surgical and audiological outcomes were recorded in the surgical notes. RESULTS: Glasgow Hearing Aid Difference Profile and Glasgow Hearing Aid Benefit Profile showed similar mean score in the active and the passive transcutaneous bone conduction devices. Client Oriented Scale of Improvement showed improvements in listening situations. Post-operative speech reception threshold showed better mean threshold in the active transcutaneous bone conduction devices group when compared with the passive transcutaneous bone conduction devices group. No device failures or surgical complications existed in either group, with the surgical time being less in the passive transcutaneous bone conduction devices group. CONCLUSION: Both devices are reliable semi-implantable transcutaneous bone conduction devices with excellent surgical and functional outcomes and patient satisfaction. Overall surgical time was much less in the passive transcutaneous bone conduction devices group with no necessity for pre-planning. This is much easier to remove with the possibility of conversion to other devices in the manufacturer's portfolio and wide-ranging wireless accessories. Further studies are needed to assess the longer-term results in a bigger population.

Streptococcus anginosus group infections: Management and outcome at a tertiary care hospital.

BACKGROUND: Data on patients with invasive Streptococcus anginosus group (SAG) infections is limited, as it's been considered commensal bacteria in the human microbiota. We conducted an analysis of SAG infections to assist clinicians in understanding their burden and clinical outcomes. METHODS: A retrospective study of medical records, identifying invasive SAG bacteria of sterile-site isolates that were managed from May 2015 to April 2017, at a tertiary care hospital in Riyadh, Saudi Arabia. Demographic data, clinical presentation, site of infection, antibiotic use, and outcome were recorded and analyzed to identify factors associated with poor outcome and/or polymicrobial growth. RESULTS: We identified 105 cases of SAG infections in adults, with 52% of the patients being male and the mean age of 52.4 years with comorbidities occurring in more than half of the cases such as diabetes (38%) and malignancy (15%). Overall mortality was 6%, and it was statistically associated with age older than 65 years, polymicrobial growth and a history of malignancy. The infection frequencies were skin and soft tissue infections (SSTI; 55%), intra-abdominal infections (24%), bacteremia (14%), genitourinary infections (8.5%), and pleuropulmonary infections (5%). Abscesses accounted for 68% of cases. Polymicrobial infection (46%) with Enterobacteriaceae and Gram-negative anaerobes coincided with SAG infection. Polymicrobial growth was significantly associated with abscess formation, intra-abdominal source of infections, and poor outcome. In addition, death in patients with SAG was statistically associated with patients older than 65 years of age and those with history of cancer or transplant. CONCLUSION: SSTIs and intra-abdominal infections are the most common clinical presentations in our cohort. Bacteremia was uncommon; however, the prognosis is less favorable. Overall susceptibility to penicillin was 91%, therefore ß-lactam antibiotics are the drug of choice and additional coverage for anaerobic and gram-negative bacteria should be considered for intra-abdominal collection and solid or organ abscesses.

Does the use of different oil sources in quail diets impact their productive and reproductive performance, egg quality, and blood constituents?

The present study investigated the impact of dietary oil sources (soybean, corn, peanut, flaxseed, olive, and sunflower oils as sources of omega 3, 6, and 9 fatty acids) on productive and reproductive traits, egg quality, hematological and biochemical blood parameters of laying Japanese quail. A total of 360 eight-week mature Japanese quail were randomly divided into 6 groups fed for 8 wk on a basal diet included with 1.5% of different oil sources. Results showed that the highest egg weights and the best feed conversion ratio (P < 0.01) were recorded for quail fed diets supplemented with 1.5% soybean and peanut oil. The highest hatchability percentages (P < 0.05) were recorded for quail fed diets supplemented with corn oil as compared to the other oils. Furthermore, diets enriched with corn, olive, or sunflower oils had higher values of blood lymphocytes (%) compared to the other treated groups. Blood total cholesterol significantly decreased in quail fed on corn, peanut, flaxseed, or olive oil sources as compared to soybean or sunflower oil groups. Immunologically, the highest levels (P < 0.001) of immunoglobulins (G and M) were recorded for quail fed on corn or olive oil sources compared to other oil sources. Quail consuming olive oil-included diets showed a significant increase in superoxide dismutase and glutathione S-transferase activities and a significant decrease on malondialdehyde level compared with those consumed the other oil sources. It could be concluded that varying the oil source can affect productive, reproductive, and health aspects of Japanese quail. Soybean oil showed good results regarding production aspects; however, olive oil was the best regarding health aspects.

Synthesis and Cytotoxic Activity of New Thiazolopyrimidine Sugar Hydrazones and Their Derived Acyclic Nucleoside Analogues.

New thienyl- or chlorophenyl-substituted thiazolopyrimidine derivatives and their derived sugar hydrazones incorporating acyclic d-galactosyl or d-xylosyl sugar moieties in addition to their per-O-acetylated derivatives were synthesized. Heterocyclization of the formed sugar hydrazones afforded the derived acyclic nucleoside analogues possessing the 1,3,4-oxadiazoline as modified nucleobase via acetylation followed by the cyclization process. The cytotoxic activity of the synthesized compounds was studied against human breast cancer MCF7 and MDA-MB-231 cell lines as well as human colorectal cancer HCT 116 and Caco-2 cell lines. High activities were revealed by compounds 1, 8, 10, 11, and 13 against Caco-2 and MCF7 cells in addition to moderate activities exhibited by other compounds against HCT116 or MDA-MB-231 cells.

'MCC' protein interacts with E-cadherin and ß-catenin strengthening cell-cell adhesion of HCT116 colon cancer cells.

E-cadherin and ß-catenin are key proteins that are essential in the formation of the epithelial cell layer in the colon but their regulatory pathways that are disrupted in cancer metastasis are not completely understood. Mutated in colorectal cancer (MCC) is a tumour suppressor gene that is silenced by promoter methylation in colorectal cancer and particularly in patients with increased lymph node metastasis. Here, we show that MCC methylation is found in 45% of colon and 24% of rectal cancers and is associated with proximal colon, poorly differentiated, circumferential and mucinous tumours as well as increasing T stage and larger tumour size. Knockdown of MCC in HCT116 colon cancer cells caused a reduction in E-cadherin protein level, which is a hallmark of epithelial-mesenchymal transition in cancer, and consequently diminished the E-cadherin/ß-catenin complex. MCC knockdown disrupted cell-cell adhesive strength and integrity in the dispase and transepithelial electrical resistance assays, enhanced hepatocyte growth factor-induced cell scatter and increased tumour cell invasiveness in an organotypic assay. The Src/Abl inhibitor dasatinib, a candidate anti-invasive drug, abrogated the invasive properties induced by MCC deficiency. Mechanistically, we establish that MCC interacts with the E-cadherin/ß-catenin complex. These data provide a significant advance in the current understanding of cell-cell adhesion in colon cancer cells.

Pancreatic stellate cells in pancreatic cancer: In focus.

Pancreatic stellate cells are stromal cells that have multiple physiological functions such as the production of extracellular matrix, stimulation of amylase secretion, phagocytosis and immunity. In pancreatic cancer, stellate cells exhibit a different myofibroblastic-like morphology with the expression of alpha-smooth muscle actin, the activated form is engaged in several mechanisms that support tumorigenesis and cancer invasion and progression. In contrast to the aforementioned observations, eliminating the stromal cells that are positive for alpha-smooth muscle actin resulted in immune-evasion of the cancer cells and resulted in worse prognosis in animal models. Understanding the cancer-stromal signaling in pancreatic adenocarcinoma will provide novel strategies for therapy. Here we provide an updated review of studies that handle the topic "pancreatic stellate cells in cancer" and recent experimental approaches that can be the base for future directions in therapy.

SerpinB2 regulates stromal remodelling and local invasion in pancreatic cancer.

Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated with reduced metastasis and prolonged survival in pancreatic ductal adenocarcinoma (PDAC) and our genomic analysis revealed that SERPINB2 is frequently deleted in PDAC. We show that SerpinB2 is required by stromal cells for normal collagen remodelling in vitro, regulating fibroblast interaction and engagement with collagen in the contracting matrix. In a pancreatic cancer allograft model, co-injection of PDAC cancer cells and SerpinB2-/- mouse embryonic fibroblasts (MEFs) resulted in increased tumour growth, aberrant remodelling of the extracellular matrix (ECM) and increased local invasion from the primary tumour. These tumours also displayed elevated proteolytic activity of the primary biochemical target of SerpinB2-urokinase plasminogen activator (uPA). In a large cohort of patients with resected PDAC, we show that increasing uPA mRNA expression was significantly associated with poorer survival following pancreatectomy. This study establishes a novel role for SerpinB2 in the stromal compartment in PDAC invasion through regulation of stromal remodelling and highlights the SerpinB2/uPA axis for further investigation as a potential therapeutic target in pancreatic cancer.

Mixed phenotype acute leukemia, B/myeloid, NOS with near-tetraploidy: a case report.

Acute leukemia in adults is usually associated with a myeloid phenotype, and less commonly presents as an acute lymphocytic leukemia. Rarely, the leukemic blast cells express more than one lineage phenotype and satisfy the diagnostic criteria for an acute leukemia of ambiguous lineage (ALAL), further subclassified as mixed phenotype acute leukemia (MPAL). Near-tetraploidy is an unusual presentation of acute leukemia where the blasts contain 80-104 chromosomes. More commonly associated with acute lymphocytic leukemia, near-tetraploidy has been described in only a limited number of cases of acute myeloid leukemias, and near-tetraploid ALAL is rare. We describe the first report of near-tetraploid MPAL, B/myeloid, not otherwise specified.

Nano-ropinirole for the management of Parkinsonism: blood-brain pharmacokinetics and carrier localization.

AIM: The aim of this study was to investigate the brain targeting potential of chitosan-coated oil in water nanoemulsions (CSNE(ROP)) delivered intranasally in haloperidol-induced Parkinson's disease rat models. METHODS: Chitosan-coated nanoemulsion (CSNE(ROP)) was developed through aqueous titration followed by a high pressure homogenization method. RESULTS: Gamma-scintigraphy study showed a significantly high mucoadhesive potential of CSNE(ROP) and least for conventional and homogenized formulations. Confocal study showed deep localization of formulations in the brain confirming the permeation potential of CSNE(ROP). Pharmacokinetic results of CSNE(ROP) in Wistar rat brain and plasma showed a significantly high (p** < 0.005) AUC0→24 and amplified Cmax over i.v treatment group. Neurobehavioral activity (rotarod and swim tests) and biochemical parameters (glutathion, TBARS and SOD) corroborated well with the pharmacokinetic results. The order of dopamine recovery in haloperidol-induced Wistar rats was found to be (i.n)CSNEROP group>(i.n)SolnROP group>(i.v)SolnROP group>haloperidol group. CONCLUSIONS: Finally, the investigation demonstrated that intranasal delivery of mucoadhesive nanocarrier might play as a potential candidate in the management of Parkinson's disease and related brain disorders.

Hyponatraemia in cancer: association with type of cancer and mortality.

Hyponatraemia is common in patients with cancer. The objectives of this study are to investigate the severity distribution of hyponatraemia and its association with mortality. We retrospectively reviewed medical records for patients admitted to a national centre for cancer care and research in Qatar between 2008 and 2012. A model was built through multivariate analyses to investigate the role of hyponatraemia in mortality. Patients were grouped into those who had moderate-severe hyponatraemia (Na < 130) and those who only had normal-mild hyponatraemia (Na ≥ 130). A total of 2048 patients were included in this study. Prostate (57.1%), pancreatic (50%), liver (49%) and lung (40.2%) cancers showed the highest frequency of moderate-severe hyponatraemia, while breast cancer showed the lowest frequency at 23.5%. In the multivariate analyses, patients with moderate-severe hyponatraemia (Na < 130 mmol/L) were 4.28 times more likely to die than those with normal-mild hyponatraemia (Na ≥ 130) (P < 0.05). The present study shows that hyponatraemia is a common electrolyte disturbance among hospitalised patients with cancer diagnoses. The severity of hyponatraemia was a statistically significant independent factor associated with higher in-hospital mortality. This is in accordance with the reported literature and emphasises the importance of early diagnosis and correction of hyponatraemia.

Penile epidermal inclusion cyst.

We report a case of epidermal inclusion cyst in a 32-year-old male. This was a complication of circumcision that was neglected over years to form stones and urethrocutaneous fistula. Complete excision of the cyst and repair of the fistula were performed successfully. Histopathological examination confirmed our diagnosis.

A rapid improved method for sexing embryo of water buffalo.

The objective of the experiment of this paper is to develop and improve in the sexing method for preimplantation embryos of water buffalo (Bubalus bubalis) using loop-mediated isothermal amplification (LAMP) reaction. Embryo sexing has been recognized to control effectively the sex of offspring in the embryo transfer industry. A rapid and simple detection system was established by adding ethidium bromide (EB) or 5 µl of CuSO4 (3M) to the product of LAMP reaction. The result of these additions after 2 min was a color change and a precipitate. It could be employed as an alternative method in the detection of the reaction products in place of the time consuming electrophoresis or the turbidity meter. The in vitro produced buffalo embryos were divided into one to eight pieces using a microblade attached to a micromanipulator. The cell number in each piece was counted before sexing. Sexing of DNA samples extracted from one to five biopsies cells was performed by LAMP. After biopsy, the remaining part of the embryos was used to confirm the sex by polymerase chain reaction (PCR). Fifty buffalo embryos were used and the accuracy of sex prediction was 100% when the blastomeres dissociated from a morula exceeds three. In conclusion, the present procedure without turbidity meter and electrophoresis was reliable and applicable for sexing the water buffalo embryos.