Molecular characterization of a rare case of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 rearrangements.

Quadruple-hit lymphomas are extremely rare non-Hodgkin lymphomas with a reported dismal prognosis in the few reported cases. A "quadruple hit" has been defined by the presence of concurrent MYC, BCL2, BCL6, and CCND1 chromosomal rearrangements. We report a new case of a quadruple hit lymphoma in a 73-year-old Hispanic man who presented with an enlarging left-sided neck mass. Computed tomography showed a 1.9-cm mass in left the tonsil with bulky cervical lymphadenopathy. The presence of all four chromosomal rearrangements can reportedly occur with disease progression in both diffuse large B-cell lymphomas and mantle cell lymphomas. Further characterization of the tumor by next-generation sequencing may be of benefit to delineate between these two possibilities. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing were used to confirm and classify the diagnosis. Histologic sections of the cervical lymph node demonstrated an atypical lymphoid infiltrate with large and pleomorphic cells, which were positive for CD20, CD10, BCL1 (Cyclin D1), BCL2, BCL6, and cMYC and negative for CD5 and SOX11 on immunohistochemistry with a Ki-67 proliferative index of 70%. FISH demonstrated MYC, BCL2, BCL6, and CCND1 rearrangements and the diagnosis of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 was rendered. Our patient was treated with dose adjusted etoposide, doxorubicin, cyclophosphamide, prednisone, and rituximab chemotherapy and has been in remission for 20 months.

Recurrent Gastrointestinal Stromal Tumor With Chondroid Differentiation After Imatinib Therapy: An Unusual Case and Literature Review.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract and is most commonly seen in the stomach. The standard treatment for patients with advanced GISTs include both surgical resection and imatinib therapy. There have been cases that document the alterations of patients' GIST histomorphology both with primary GIST prior to imatinib therapy and with recurrent GIST after imatinib therapy. However, there has been no documented case of a patient who has recurrent GIST with chondroid differentiation at the primary site after imatinib therapy. In this article, we report an incidental finding of a 58-year-old patient who had two treatments of imatinib therapy prior to surgical resection of her recurrent GIST in her stomach. We also explore through a mini-literature review the various cases of GIST with chondroid differentiation that have been reported to compare the histomorphology, immunophenotype, and patient demographic of these cases. This article is significant for reporting a rare finding of GIST after imatinib therapy and highlights the various presentations that GIST could acquire after imatinib therapy that exclude another malignant process, such as chondrosarcoma.

Disseminated Anaplastic Lymphoma Kinase (ALK)-Positive T-cell Lymphoma Involving the Uterus and Cervix: A Case Report.

Primary or secondary non-Hodgkin lymphomas (NHLs) involving the female gynecologic tract are rare. T-cell subtypes are further rare and portend a worse prognosis. We present a case of a 23-year-old female presenting with a cervical mass accompanied by constitutional symptoms and abnormal vaginal bleeding. Immunohistochemistry studies revealed the presence of disseminated T-cell non-Hodgkin lymphoma that was anaplastic lymphoma kinase (ALK)-positive. The patient demonstrated a complete response to systemic chemotherapy initially and again after the relapse of the disease one year after diagnosis. To our knowledge, this is the first case of an ALK-positive T-cell lymphoma with secondary involvement of the uterus and cervix; all previously published cases of this histologic subtype in the gynecologic tract describe primary disease of the vagina. This case emphasizes the importance of immunohistochemistry studies inclusive of T-cell and B-cell markers when evaluating biopsies from cervical tumors to render the appropriate diagnosis and guide systemic therapy.

Isolated Myeloid Sarcoma Masquerading as Scattered Abscesses in a Septic Patient: A Case Report and Literature Review.

Introduction: Myeloid sarcoma (MS) is also known as chloroma, extramedullary acute myeloid leukemia (AML), or granulocytic sarcoma. MS is a rare extramedullary infiltration of myeloid cells, most commonly collecting in the skin and causing a small number of localized lesions. It is strongly associated with AML; however, MS more commonly occurs after diagnosis of AML is previously established or after previous treatment of AML. Case Presentation: This case describes a patient with an atypical presentation of MS with no known history of AML and up to 18 lesions identified on CT scan that were previously being monitored for months by her primary care physician. She presented with sepsis attributed to choledocholithiasis versus bacteremia from scattered abscesses versus osteomyelitis of her left knee; nonetheless, lactic acid failed to improve after common bile duct stent with biliary sphincterotomy/dilation or with incision and drainage and empiric antibiotics. Core needle biopsy of her left abdominal sidewall was eventually positive for MS, but she unfortunately developed multiorgan failure with symptomatic hypercalcemia refractory to treatment and ultimately decided to go to comfort care rather than pursue further workup and treatment. Although bone marrow biopsy was ultimately not performed to rule out synchronous AML, this is likely a case of isolated MS due to her scattered skin lesions being present for months prior to hospitalization and acute illness. Conclusion: This case highlights the importance of maintaining MS in the differential diagnosis and the importance of early diagnostic core needle biopsy for patients with persistent skin lesions of unknown origin.

Gastrointestinal Mucormycosis: A Clinical Review.

Mucormycosis is a devastating fungal infection that is usually seen in immunocompromised hosts. It is caused by fungi of the subphylum Mucoromycotina, order Mucorales, with most cases caused by Mucor, Rhizopus, or Rhizomucor species. It can involve any organ system and can disseminate in severe cases. Lately, there has been an increased number of reports for mucormycosis infection in immunocompetent patients. Gastrointestinal system involvement is rare compared to other organ systems but has been increasingly reported in the literature. Mucormycosis can affect any part of the gastrointestinal tract and lead to different presentations depending on the area of involvement. Due to the paucity of the condition, there has been no specific guidelines on how to treat gastrointestinal mucormycosis. In this review, we discuss the risk factors of gastrointestinal mucormycosis, clinical presentation, approach to diagnosis, and most recent treatment modalities for gastrointestinal mucormycosis.

Cultivation of blue green algae (Arthrospira platensis Gomont, 1892) in wastewater for biodiesel production.

The production of biodiesel has become an important issue in the effort to reduce gas emissions due to the climate change crisis; therefore, algae have widely used to produce biodiesel for energy sustainability. The present study represented an effort to assess the ability of the alga Arthrospira platensis to produce fatty acids involved in biofuel (diesel) by cultivation in Zarrouk media enriched with different municipal wastewater concentrations. Wastewater was used in different concentrations (5, 15, 25, 35 and 100% [control]). Five fatty acids from the alga were determined and included in the present study. These were inoleic acid, palmitic acid, oleic acid, gamma-linolenic acid, and docosahexaenoic acid. Impact of different cultivation conditions were studied in terms of observed changes in growth rate, doubling time, total carbohydrate, total protein, chlorophyll a, carotenoids, phycocyanin, allophycocyanin, and phycobiliproteins. Results showed an increase in the values of growth rate, total protein content, chlorophyll a, and levels of carotenoids at all treatments except for carbohydrate content, which decreased with an increasing concentration of wastewater. The high value of doubling time (11.605 days) was recorded at treatment 5%. Fatty acids yields were increased at treatment 5% and 15%. The highest concentrations of fatty acids were 3.108 mg/g for oleic acid, gamma-linolenic acid (28.401 mg/g), docosahexaenoic acid (41.707 mg/g), palmitic acid (1.305 mg/g), and linoleic acid (0.296 mg/g). Moreover, the range of phycocyanin (0.017-0.084 mg/l), allophycocyanin (0.023-0.095 mg/l), and phycobiliproteins (0.041-0.180 mg/l) were obtained in treatment with 15-100%, respectively. Cultivation with municipal wastewater reduced the values of nitrate, phosphate, and electrical conductivity as well as increased dissolved oxygen. Maximum electrical conductivity was recorded in untreated wastewater with algae, while the highest level of dissolved oxygen was noted at 35% concentration. The use of the household wastewater is more environmentally friendly as an alternative of the traditional cultivation techniques used for long-term for biofuel production.

Metal-Free Aerobic C-N Bond Formation of Styrene and Arylamines via Photoactivated Electron Donor-Acceptor Complexation.

This study processes a facile and green approach for the Markovnikov-selective hydroamination of styrene with naphthylamine through irradiation with UV LED light (365 nm) via an electron donor-acceptor complexation between naphthylamines and oxygen in situ. This protocol showcases the synthetic potential for aerobic C-N bond formation without using a metal catalyst and photosensitizer. Three naphthylamines were examined and afforded desired C-N bond formation product in moderate yield.

Two-Step Synthesis, Structure, and Optical Features of a Double Hetero[7]helicene.

A novel double aza-oxa[7]helicene was synthesized from the commercially available N1,N4-di(naphthalen-2-yl)benzene-1,4-diamine and p-benzoquinone in two steps. Combining the acid-mediated annulation with the electrochemical sequential reaction (oxidative coupling and dehydrative cyclization) afforded this double hetero[7]helicene. Moreover, the structural and optical features of this molecule have been studied using X-ray crystallographic analysis, and the absorption and emission behaviors were rationalized based on DFT calculations.

Gastrointestinal manifestations, risk factors, and management in patients with post-transplant lymphoproliferative disorder: A systematic review.

BACKGROUND: Patients with a history of solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT) are at an increased risk of developing post-transplant lymphoproliferative disorder (PTLD). The gastrointestinal (GI) tract is commonly affected as it has an abundance of B and T cells. AIM: To determine typical GI-manifestations, risk factors for developing PTLD, and management. METHODS: Major databases were searched until November 2021. RESULTS: Non-case report studies that described GI manifestations of PTLD, risk factors for developing PTLD, and management of PTLD were included. Nine articles written within the last 20 years were included in the review. All articles found that patients with a history of SOT, regardless of transplanted organ, have a propensity to develop GI-PTLD. CONCLUSION: GI tract manifestations may be nonspecific; therefore, consideration of risk factors is crucial for identifying GI-PTLD. Like other lymphoma variants, PTLD is very aggressive making early diagnosis key to prognosis. Initial treatment is reduction of immunosuppression which is effective in more than 50% of cases; however, additional therapy including rituximab, chemotherapy, and surgery may also be required.

Primary Vaginal Adenocarcinoma of Intestinal-Type: A Case Report of a Rare Tumor With Review of Histology, Differential Diagnosis, and Literature.

Intestinal-type adenocarcinoma is a rare primary vaginal carcinoma. Vaginal adenocarcinomas are most frequently a metastatic lesion, and less commonly, have clear cell histology and occur in young women with diethylstilbestrol (DES) exposure in utero. Due to the limited diagnostic power of immunohistochemistry (IHC) in differentiating primary from metastatic adenocarcinoma of the vagina, clinical and radiological correlation is critical in this scenario. The prognosis of this tumor depends on the patient's age, tumor stage, tumor differentiation, lymph node status, and distant metastasis. Several treatment modalities are present depending on the tumor stage. We present a case of primary adenocarcinoma of the vagina and describe the histopathologic features including the immunoprofile of the tumor and discuss the clinicopathologic features, differential diagnosis, diagnostic challenges, and a brief overview of the literature about age, size, site, immunohistochemical staining, and DES exposure.

Desert soil fungi isolated from Saudi Arabia: cultivable fungal community and biochemical production.

Desert soils harbor fungi that have survived under highly stressed conditions of high temperature and little available moisture. This study was designed to survey the communities of cultivable fungi in the desert soils of the Arabian Peninsula and to screen the fungi for the potentially valuable antioxidants (flavonoids, phenols, saponins, steroids, tannins, terpenoids, and alkaloids) and enzymes (cellulase, laccase, lipase, protease, amylase, and chitinase). Desert soil was sampled at 30 localities representing different areas of Saudi Arabia and studied for physico-chemical soil properties. Five types of soil texture (sand, loamy sand, sandy loam, silty loam, and sandy clay loam) were observed. A total of 25 saprotrophic species was identified molecularly from 68 isolates. Our survey revealed 13 culturable fungal species that have not been reported previously from Arabian desert soils and six more species not reported from Saudi Arabian desert soils. The most commonly recorded genera were Aspergillus (isolated from 20 localities) and Penicillium (6 localities). The measurements of biochemicals revealed that antioxidants were produced by 49 and enzymes by 52 isolates; only six isolates did not produce any biochemicals. The highest biochemical activity was observed for the isolates Fusarium brachygibbosum and A. phoenicis. Other active isolates were A. proliferans and P. chrysogenum. The same species, for instance, A. niger had isolates of both high and low biochemical activities. Principal component analysis gave a tentative indication of a relationship between the biochemical activity of fungi isolated from soil and soil texture variables namely the content of silt, clay and sand. However, any generalizable relation between soil properties and fungal biochemical activities cannot be suggested. Each fungal isolate is probable to produce several antioxidants and enzymes, as shown by the correlation within the compound groups. Desert soil warrants further research as a promising source of biochemicals.

Delayed acute myocarditis with COVID-19 infection.

Myocardial injury occurs in 20% to 30% of hospitalized patients with COVID-19 infection, and cardiovascular complications contribute to approximately 40% of all COVID-19-related deaths. Most cases of myocarditis related to COVID-19 infection occur in the acute phase of infection and are self-limited. We describe a case of delayed-onset fulminant myocarditis that developed 5 weeks after mild COVID-19 infection leading to cardiogenic shock and the need for mechanical circulatory support. Our case illustrates how myocarditis can occur as a late complication of COVID-19 infection, even in those with a mild initial course.

Vaginal Endosalpingiosis: A Case Report and Literature Review.

Endosalpingiosis is a benign condition with unclear pathogenesis and clinical significance and is defined as the presence of ectopic fallopian tube-like epithelium. It can be found in multiple locations, most commonly in the pelvic peritoneum covering the ovaries, uterus, and fallopian tubes, and less commonly found in the lymph nodes, omentum, appendix, cervix, vulva, or vagina. It is difficult to distinguish from endometriosis by gross appearance or localization, and theories propose that tissues of the secondary Mullerian system may undergo a metaplastic transformation, for example, from endosalpingiosis to endometriosis, which contributes to the debated association of endosalpingiosis with chronic pelvic pain. Additionally, there is evidence demonstrating a close association with reproductive tract neoplasms. We report the clinical course, diagnosis including pathology, follow-up, and the treatment plan of vaginal endosalpingiosis in a 34-year-old woman presenting with a chronic painful right-sided vaginal mucosal ulceration, dyspareunia, and foul-smelling vaginal discharge. To our knowledge, this is the second reported case of vaginal endosalpingiosis and the first case with this presentation.

Fabrication of Biohybrid Nanofibers by the Green Electrospinning Technique and Their Antibacterial Activity.

The development of bioactive polymer nanofiber sheets based on eco-friendly components is required to meet the needs of various medical applications as well as to preserve the environment. This study aimed to fabricate biohybrid nanofibers based on water-soluble polymers and aqueous extract of myrrh. The myrrh extract was incorporated into poly(vinyl alcohol)/tragacanth gum nanofiber mats (myrrh@PVA/TG) by the green electrospinning technique. Various characteristics of the prepared fibers such as morphology, fiber diameter distribution, crystallinity, and thermal stability were studied. The results confirmed that the morphology of biohybrid nanofibers was uniform without beads and tragacanth gum plays an important role in controlling the average diameter of fibers and the crystallinity. The antibacterial properties of the developed biohybrid nanofibers were investigated against common pathogens of Gram-positive and Gram-negative bacteria by the standard disc diffusion method. A significant antibacterial activity was observed toward bacterial strains after incorporation of aqueous myrrh extract into nanofibers, which increased on increasing the extract ratio. Due to their eco-friendly components and significant antibacterial activity, the prepared biohybrid nanofibers will open new avenues toward incorporating aqueous herbal extracts into degradable polymer fibers for use in many antibacterial applications.

Green Synthesis of Silver Nanoparticles Using Olea europaea Leaf Extract for Their Enhanced Antibacterial, Antioxidant, Cytotoxic and Biocompatibility Applications.

Herein, we report the green synthesis of silver nanoparticles (OE-Ag NPs) by ecofriendly green processes using biological molecules of Olea europaea leaf extract. Green synthesized OE-Ag NPs were successfully characterized using different spectroscopic techniques. Antibacterial activity of OE-Ag NPs was assessed against four different bacteriological strains using the dilution serial method. The cytotoxic potential was determined against MCF-7 carcinoma cells using MTT assay in terms of cell viability percentage. Antioxidant properties were evaluated in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. Biocompatibility was further examined by incubating the synthesized NPs with hMSC cells for 24 h. The results were demonstrated that synthesized OE-Ag NPs presented excellent log10 reduction in the growth of all the tested bacterial strains, which as statistically equivalent (p > 0.05) to the standard antibiotic drug. Moreover, they also demonstrated excellent cytotoxic efficacy against the MCF-7 carcinoma cells compared to plant lead extract and Com-Ag NPs. Green synthesized OE-Ag NPs appeared more biocompatible to hMSC and 293T cells compared to Com-Ag NPs. Excellent biological results of the OE-Ag NPs might be attributed to the synergetic effect of NPs' properties and the adsorbed secondary metabolites of plant leaf extract. Hence, this study suggests that synthesized OE-Ag NPs can be a potential contender for their various biological and nutraceutical applications. Moreover, this study will open a new avenue to produce biocompatible nanoparticles with additional biological functionalities from the plants.

Primary Cutaneous Leiomyosarcoma of the Lower Extremity: A Case Report and Literature Review.

Cutaneous leiomyosarcoma is a rare soft-tissue sarcoma that appears non-specific clinically and often is misdiagnosed as squamous cell carcinoma. We report the case of a 59-year-old Caucasian male with a grade I leiomyosarcoma tumor on his lower extremity with no previous history of local trauma. The tumor is composed of highly atypical spindle cells with pleomorphic nuclei and mitotic activity on hematoxylin and eosin stains. The diagnosis is confirmed with immunohistochemistry staining positive for smooth muscle actin, vimentin, and desmin. Due to high recurrence rates, the prognosis for leiomyosarcomas remains poor and requires close follow-up to prevent progression.

Epigenetic Modifiers Affect the Bioactive Compounds Secreted by an Endophyte of the Tropical Plant Piper longum.

Seven endophytic fungi were isolated from the tropical medicinal plant Piper longum L. After preliminary screening, Phomopsis heveicola was selected for the epigenetic activation treatments. The antibacterial, antifungal, and antioxidant potentials of crude extracts obtained from the treatments (with and without epigenetic modifiers) were analyzed in vitro. The extracts inhibited growth of the human pathogens Pseudomonas aeruginosa, Shigella sonnei, Streptococcus pyogenes, and Salmonella typhi, as well as the phytopathogens Puccinia recondita, Rhizoctonia solani, Phytophthora infestans, and Botrytis cinerea. Furthermore, DPPH-scavenging activity was higher in valproic acid treated extracts. Volatile chemicals with known biological activities (measured with GC-MS/MS), were released in the valproic acid treatment. The antimicrobial potentials of the extracts were confirmed using MRM/MS analysis. The experiments revealed a new promising endophytic fungus, P. heveicola, to be utilized in biological plant protection and in biomedical applications.

Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies.

A novel coronavirus responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, to test existing drugs as inhibitors of SARS-CoV-2 main protease is a good approach. Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules. The flavonoids chemical structures were downloaded from PubChem and protease structure 6LU7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the SARS-CoV-2 protease and could be further investigated by in vitro and in vivo experiments for further validation. MD simulations were further performed to evaluate the dynamic behavior and stability of the protein in complex with the three best hits of docking experiments. Our results indicate that the rutin is a potential drug to inhibit the function of Chymotrypsin-like protease (3CL pro) of Coronavirus.

A high-fat diet enriched in medium chain triglycerides triggers hepatic thermogenesis and improves metabolic health in lean and obese mice.

Obesity, liver steatosis and type 2 diabetes are major diseases partly imputed to energy-dense diets rich in long chain triglycerides (LCT). The search for bioactive nutrients that help to overcome metabolic diseases is a growing field. In this regard, medium chain triglycerides (MCT) were shown to promote lipid catabolism and to stimulate brown adipose tissue thermogenesis. The objective of our study was to evaluate if the replacement of LCT by MCT in high-fat diets could prevent and/or reduce metabolic disorders. For this purpose, two cohorts of C57BL/6 mice were fed during 10 weeks with three isocaloric high-fat diets with variable MCT content. Cohort A was composed of lean mice while cohort B was composed of obese, insulin resistant mice. In cohort A, replacement of LCT by MCT preserved metabolic health, in part by triggering hepatic thermogenesis. We further found that medium chain fatty acids promote thermogenesis markers within cultured hepatocytes in a FFAR1/GPR40-dependent manner. In cohort B, high-fat diets enriched in MCT promoted body fat depletion and caused metabolic health improvement, together with the induction of thermogenesis markers in the liver as well as in subcutaneous white adipose tissue. Our study supports that replacement of LCT by MCT in high-fat diets improves the metabolic features associated with obesity.

Hexanoic, Octanoic and Decanoic Acids Promote Basal and Insulin-Induced Phosphorylation of the Akt-mTOR Axis and a Balanced Lipid Metabolism in the HepG2 Hepatoma Cell Line.

Metabolic illnesses such as non-alcoholic fatty liver disease (NAFLD) are in constant increase worldwide. Highly consumed long chain fatty acids (LCFA) are among the most obesogenic and steatogenic nutrients. Hepatic steatosis is associated with several complications such as insulin resistance. Growing evidence points to medium chain fatty acids (MCFA), more efficiently oxidized than LCFA, as a promising dietary alternative against NAFLD. However, reports on the hepatic effects of MCFA are sometimes conflicting. In this study we exposed HepG2 cells, a human hepatocellular model, to 0.25 mM of hexanoic (C6), or octanoic (C8), and decanoic (C10) acids separately or in a C8 + C10 equimolar mix reflecting commercially available MCFA-rich oils. We found that C6, a poorly studied MCFA, as well as C8 and C10 did not provoke the deleterious lipid anabolism runaway typically induced by LCFA palmitate. MCFA tended, instead, to promote a balanced metabolic profile and were generally non-cytotoxic. Accordingly, mitochondrial integrity was mostly preserved following MCFA treatment. However, treatments with C8 induced a mitochondrial membrane potential decrease, suggesting prolonged exposure to this lipid could be problematic. Finally, MCFA treatments maintained optimal insulin sensitivity and even fostered basal and insulin-dependent phosphorylation of the Akt-mTOR pathway. Overall, MCFA could constitute an effective nutritional tool to manage liver steatosis and hepatic insulin resistance.