South Africa is prone to droughts and is heavily dependent on stored water resources. Few studies in South Africa have investigated the impact of drought on water quality when rainfall resumes and ...reservoir sediments are rewet. Other research has shown that several negative impacts may occur with rewetting, including eutrophication, and acidification with increased metal solubility. In this study, the impact of drying and rewetting sediments on the mobility of nutrients and metals is explored using sediments from Loskop Reservoir. Rarely exposed sediments were collected from three sites, dried at 35 degreesC for 36 days, and then rewet under aerobic conditions. Filtered water samples were collected on Days 1, 2,4, 7, 11 and 16 following rewetting, and analysed for NH4+, NO3-, NO2-, total N, total P, PO43-, dissolved Al, Fe, Mn, and SO42-. Results were expressed as mass/m2, and were compared to reference (non-drought) treatments that were maintained under saturated conditions. Acute toxicity tests were performed using Daphnia magna to establish if toxic effects were associated with changes in water quality following sediment rewetting. Following rewetting, elevated SO42- indicated the mobilisation of acid from sulfide oxidation, with an associated reduction in pH. Nitrification was evident as high quantities of organic N and NH4+ were initially released, followed by increases in NO2- + NO3-. Total P increased, but PO43- reduced. This was attributed to complexes formed between PO43- and Fe (FePO4) and Al (AlPO4). Amounts of Fe and Al released were lower following rewetting due to the formation of relatively immobile (hydr)oxides. In contrast, Mn increased substantially reaching maximum values > 2 300 mg/m2 (14 000 mug/L). There were no acute toxic effects observed to D. magna. This study highlights the potential for acidification, mobilisation of nutrients, SO42-, and Mn following rewetting of reservoir sediments under aerobic conditions. This information may be incorporated into reservoir and catchment management plans in the form of revised water quality guidelines and a better ability to predict how drought impacts water quality in our stored water resources.
Abstract
Introduction/Objective
Blinatumomab is a monoclonal antibody directed against CD19/CD3 utilized for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia ...(ALL) and for the treatment of B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥0.1%. Although Blinatumomab treatment has shown better overall survival, progression-free survival, and complete remission when compared to chemotherapy, most patients have a relapse and ultimately succumb to the disease. Interestingly, there are a number of cases reporting relapse in extramedullary places. The mechanisms for relapse in these unusual extramedullary sites are not well-understood. We herein report a case of a 20-year-old African American male with primary refractory Philadelphia-negative (Ph-) precursor B cell ALL with MLL rearrangement, who received treatment with Blinatumomab after achieving morphological remission with a pediatric-inspired regimen but found to be MRD +.
Methods/Case Report
A 20 year old African American male was found to have B cell precursor ALL. It was found to be Ph-. While initally receiving vincristine, prednisone, and aspariginase, the ALL proved to be refractory to treatment. Blinatumomab was used as second line therapy after the first failed remission. The patient remained with morphological response; however, remained MRD+ after three cycles of Blinatumomab. During the fourth cycle, the patient presented with back pain and lower extremity weakness. A spine MRI revealed an extradural mass in the thoracic spine causing cord compression. A thoracic laminectomy with partial removal of the mass, followed by radiation, was performed with improvement of symptoms. Pathology results of the extradural mass revealed a myeloid sarcoma with MLL rearrangement.
Results (if a Case Study enter NA)
NA
Conclusion
This case report demonstrates how patients treated with blinatumomab can have relapse in unusual extramedullary places. The possibility of leukemia manifesting in extramedullary sites should always be kept in mind by clinicians treating patients with Blinatumomab. The mechanisms of resistance against Blinatumomab are not well- understood and need further elucidation.
Abstract
Introduction/Objective
Hodgkins lymphoma is a B cell lymphoproliferative disease, with most cases showing PAX5 positivity. Very few PAX5 negative hodgkins lymphoma cases have been described. ...We describe four PAX5 negative nodular sclerosing hodgkins lymphoma cases. All received standard chemotherapy, three received additional chemotherapeutic agents. Exploring these rare cases can be invaluable in characterizing and later treating his atypical presentation.
Methods/Case Report
Four cases of Hodgkins Lymphoma were diagnosed between 2017 and 2020. Two males and two females between 31 and 80 year old. Case 1 was a 31 year old male with a left neck lymphadenopathy that revealed nodular sclerosing Hodgkins lymphoma without bone marrow involvement. IHC staining revealed CD15, CD30, fascin and MUM-1 positivity, and PAX5 negativity. He received Doxorubicin, Vinblastine, Dacarbazine (AVD) and Brentuximab with radiation, and later brentuximab with bendamutine. Follow up PET-CT and left axillary node excisional biopsy found nodular sclerosing classic hodgkins. He received Ifosfamide, Carboplatin, and Etoposide.
Case 2 was a 37 year old male with bilateral mediastinal lymphadenopathy that demonstrated nodular sclerosing Hodgkins lymphoma on biopsy. The cells were CD15, CD30 positive, and PAX5 negative. He received AVD with bleomycin (ABVD), and field radiation with excellent response and is currently under surveillance. Case 3 was a 31 year old female with a left chest mass that demonstrated nodular sclerosing Hodgkins lymphoma. The cells were positive for MUM1, CD30 and fascin and negatively for CD15 and PAX5. She received ABVD. Case 4 was an 80 year old female with prior stage IV gastric diffuse large B cell lymphoma treated with Rituximab, Cyclophophamide, Vincristine, and Prednisone and achieved remission. She later developed neck masses that were biopsied revealing classic Hodgkins lymphoma. The cells stained for CD30, for CD15, and were negative for PAX5. She was started on AVD and is on palliative care.
Results (if a Case Study enter NA)
NA
Conclusion
Most hodgkins lymphomas are PAX5 positive. We found four cases of PAX5 negative Hodgkins lymphoma. Incidentally, all were of the nodular sclerosing subtype. All cases were treated with recommended chemotherapy and/or radiation. All four cases had good response with reduction in disease burden. This finding suggests that PAX5 negativity still allows the nodular sclerosing hodgkins lymphoma to be responsive to standard treatment modalties.
Diets incorporating different levels of corn gluten meal replacement using biofuel algae or Spirulina protein at 0%, 25%, 50%, 75% and 100% were evaluated for larval/juvenile stage of Nile tilapia ...(Oreochromis niloticus). Fish averaging 0.02 g were divided into groups of 50. There were three replicates per every dietary treatment that were fed one of six diets for 11 weeks. Corn gluten protein was replaced with algae on the protein basis. All diets were supplemented with 1.5% lysine and 0.5% methionine. The experimental diets were formulated to contain 37 ± 2.8% protein and 14 ± 4.3% lipid in the form of fish oil and soybean lecithin (phospholipids source). The results indicated that algae positively affected feed consumption and fish growth up to the 50% replacement and then performance was depressed. Significant differences in concentration of individual minerals (Al, Fe, Zn and Cu) in the whole fish body were found. Mineral composition of algae might have affected growth when diets which contained more than 75% of plant protein were replaced with microalgae. These findings suggest that up to 50% of dietary corn gluten meal protein can be replaced with microalgae which significantly enhance fish growth.
To determine the prevalence and extent of impairments impacting health-related quality of life among survivors of COVID-19 who required mechanical ventilation, 6 months after hospital discharge.
...Multicenter, prospective cohort study, enrolling adults 18 years old or older with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection who received mechanical ventilation for 48 hours or more and survived to hospital discharge. Eligible patients were contacted 6 months after discharge for telephone-based interviews from March 2020 to December 2020. Assessments included: Montreal Cognitive Assessment-Blind, Hospital Anxiety and Depression Scale, Impact of Event Scale-6, EuroQOL 5 domain quality-of-life questionnaire, and components of the Multidimensional Dyspnea Profile.
Two tertiary academic health systems.
Of 173 eligible survivors, a random sample of 63 were contacted and 60 consented and completed interviews.
None.
Mean age was 57 + 13 years and mean duration of invasive mechanical ventilation was 14 + 8.2 days. Six months post-discharge, 48 patients (80%; 95% CI, 68-88%) met criteria for post-intensive care syndrome (PICS), with one or more domains impaired. Among patients with PICS, 28 (47%; 95% CI, 35-59%) were impaired in at least 2 domains, and 12 (20%; 95% CI, 12-32%) impaired in all three domains. Significant symptoms of post-traumatic stress were present in 20 patients (33%; 95% CI, 23-46%), anxiety in 23 (38%; 95% CI, 27-51%), and depression in 25 (42%; 95% CI, 30-54%). Thirty-three patients (55%; 95% CI, 42-67%) had impairments in physical activity; 25 patients (42%; 95% CI, 30-54%) demonstrated cognitive impairment.
Eighty percent of COVID-19 survivors who required mechanical ventilation demonstrated PICS 6 months after hospital discharge. Patients were commonly impaired in multiple PICS domains as well as coexisting mental health domains.
Abstract
Introduction/Objective
Adrenal Cortical Carcinoma (ACC) is a rare malignant neoplasms originating from adrenal cortical tissue with an annual incidence rate of 1 to 2 cases per million ...individuals. These tumors have poor prognosis with 5-year disease free survival being 30% after complete resection in Stage I to Stage III patients. Hence, there is a need for identifying prognostic markers for effective management of disease in these patients.
Methods
We analyzed the data in The Cancer Genome Atlas of 1141 ACC individuals, using cbioportal.org, a web- based platform for analysis of large-scale cancer genomics data sets, and derived correlation between prognosis and genetic alterations in approximately 51,309 genes.
Results
We identified 15 signature genes (NOTCH1, TP53, ZNRF3, LRP1, KIF5A, MDM2, LETMD1, MTOR, NOTCH3, RERE, SMARCC2, LDLR, HRNR, AVPR1A and PCDH15), alterations in which indicated a poor prognosis for ACC individuals. Analysis of 15 signature genes demonstrated that disease specific median survival for the patients with ACC, was reduced to 39.5 months (p value < 8 x 10 -9 and sensitivity of 93%) when any one or more of these genes was altered. Whereas, disease specific median survival was greater than 180 months (90% survival being 180 months) with no alteration in our signature genes. In addition, our analysis of our signature genes demonstrates reduced overall survival, disease free survival and progression free survival in individuals having alterations in our signature genes. Moreover, our set of 15 genes belonged mainly to MDM2-TP53, NOTCH and mTOR pathways, and small molecule modulators of these pathways are in process of development.
Conclusion
Our 15 gene signature was not only able to predict poor prognosis in ACC, but also has the potential to serve as a molecular marker set for initiation of NOTCH and mTOR specific targeted therapies in these patients.
Lipid concentration and fatty acid composition of common prey species or taxonomic groups from four distinct regions of Lake Michigan were quantified (n = 894). We used a combination of parametric ...and nonparametric statistics to assess the differences in fatty acid signatures (FAS) among species and to evaluate intraspecies variation relative to interspecies variation in FAS. Discriminant function analysis performed on 13 species or taxa groups using the 18 most abundant fatty acids revealed clear separation among taxa, with overall classification success reaching 89%. Species were readily distinguished based on their overall fatty acid profile in spite of intraspecies variation (temporal, regional, and size-related). Among species sampled, pelagic and benthic clusters were formed based on the degree of fatty acid profile similarity. In alewife (
Alosa pseudoharengus
) and round goby (
Neogobius melanostomus
), fatty acid compositions differed with fish size, sampling location, and temporal variation; however, the magnitude of these differences was small relative to differences between species. Our results demonstrate the utility of fatty acid signatures in studies of food webs in large freshwater ecosystems. This study is also a necessary first step toward development of mechanistic research that investigates the effects of variation in fatty acids within the prey base on top predators.
Abstract
Introduction/Objective
The anaplastic lymphoma kinase (ALK) gene is a receptor tyrosine kinase gene located in the 2p23.2 region. Normally, dimerization of ALK receptor by binding to its ...ligand activates the ALK receptor by autophosphorylation of c-termius and activates downstream PI3K, MAPK and JAK3 pathways. The ALK gene is abnormally hyperactivated by fusion of the 3’ half containing the kinase domain with 5’ portion of other genes, resulting in the ligand independent dimerization and activation of the ALK receptor. The tumors harboring these translocations are termed as ALK-positive tumors and can be treated with ALK inhibitors.
Methods
We analyzed the status of clinically relevant ALK fusion driver mutations in 230 different cancer studies, containing tumors from 79222 different individuals, in The Cancer Genome Atlas database (TCGA) using the cbioportal web browser.
Results
We observed that, as expected ALK-positive mutations are predominantly present in NSCLC, with EML4- ALK being the most common. In addition, we were able to identify ALK positive mutations in colorectal carcinomas, papillary thyroid carcinomas, papillary renal cell carcinomas, sarcomas and invasive ductal carcinomas of the breast. Most important, our analysis identified extremely rare ALK positive cases in salivary duct carcinomas, urothelial carcinomas, cutaneous melanomas and prostatic adenocarcinomas.
Conclusion
Our analysis identified ALK positive cases were predominant in adenocarcinoma of lung with EML4-ALK being the most common ALK positive mutation, which is also consistent with the literature. However, the ALK positive mutations were at a lower prevalence rate than that described in the literature. We attribute the lower prevalence rate to underrepresentation of the Asian population in the TCGA database. In addition, we identified extremely rare ALK positive cases in salivary duct carcinomas, melanomas and prostate cancers, thus highlighting the need for testing for these mutations in these cancers.
South Africa is prone to droughts and is heavily dependent on stored water resources. Few studies in South Africa have investigated the impact of drought on water quality when rainfall resumes and ...reservoir sediments are rewet. Other research has shown that several negative impacts may occur with rewetting, including eutrophication, and acidification with increased metal solubility. In this study, the impact of drying and rewetting sediments on the mobility of nutrients and metals is explored using sediments from Loskop Reservoir. Rarely exposed sediments were collected from three sites, dried at 35 degreesC for 36 days, and then rewet under aerobic conditions. Filtered water samples were collected on Days 1, 2,4, 7, 11 and 16 following rewetting, and analysed for NH4+, NO3-, NO2-, total N, total P, PO43-, dissolved Al, Fe, Mn, and SO42-. Results were expressed as mass/m2, and were compared to reference (non-drought) treatments that were maintained under saturated conditions. Acute toxicity tests were performed using Daphnia magna to establish if toxic effects were associated with changes in water quality following sediment rewetting. Following rewetting, elevated SO42- indicated the mobilisation of acid from sulfide oxidation, with an associated reduction in pH. Nitrification was evident as high quantities of organic N and NH4+ were initially released, followed by increases in NO2- + NO3-. Total P increased, but PO43- reduced. This was attributed to complexes formed between PO43- and Fe (FePO4) and Al (AlPO4). Amounts of Fe and Al released were lower following rewetting due to the formation of relatively immobile (hydr)oxides. In contrast, Mn increased substantially reaching maximum values > 2 300 mg/m2 (14 000 mug/L). There were no acute toxic effects observed to D. magna. This study highlights the potential for acidification, mobilisation of nutrients, SO42-, and Mn following rewetting of reservoir sediments under aerobic conditions. This information may be incorporated into reservoir and catchment management plans in the form of revised water quality guidelines and a better ability to predict how drought impacts water quality in our stored water resources.
South Africa is prone to droughts and is heavily dependent on stored water resources. Few studies in South Africa have investigated the impact of drought on water quality when rainfall resumes and ...reservoir sediments are rewet. Other research has shown that several negative impacts may occur with rewetting, including eutrophication, and acidification with increased metal solubility. In this study, the impact of drying and rewetting sediments on the mobility of nutrients and metals is explored using sediments from Loskop Reservoir. Rarely exposed sediments were collected from three sites, dried at 35 degreesC for 36 days, and then rewet under aerobic conditions. Filtered water samples were collected on Days 1, 2 ,4, 7, 11 and 16 following rewetting, and analysed for NH4+, NO3-, NO2-, total N, total P, PO43-, dissolved Al, Fe, Mn, and SO42-. Results were expressed as mass/m2, and were compared to reference (non-drought) treatments that were maintained under saturated conditions. Acute toxicity tests were performed using Daphnia magna to establish if toxic effects were associated with changes in water quality following sediment rewetting. Following rewetting, elevated SO42- indicated the mobilisation of acid from sulfide oxidation, with an associated reduction in pH. Nitrification was evident as high quantities of organic N and NH4+ were initially released, followed by increases in NO2- + NO3-. Total P increased, but PO43- reduced. This was attributed to complexes formed between PO43- and Fe (FePO4) and Al (AlPO4). Amounts of Fe and Al released were lower following rewetting due to the formation of relatively immobile (hydr)oxides. In contrast, Mn increased substantially reaching maximum values > 2 300 mg/m2 (14 000 mug/L). There were no acute toxic effects observed to D. magna. This study highlights the potential for acidification, mobilisation of nutrients, SO42-, and Mn following rewetting of reservoir sediments under aerobic conditions. This information may be incorporated into reservoir and catchment management plans in the form of revised water quality guidelines and a better ability to predict how drought impacts water quality in our stored water resources.
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