Outcomes of Ultrafiltration in community-based hospitals.

OBJECTIVE: We sought to examine outcomes of ultrafiltration in real world community-based hospital settings. BACKGROUND: Ultrafiltration (UF) is an accepted therapeutic option for advanced decompensated heart failure (ADHF). the feasibility of UF in a community hospital setting, by general cardiologists in a start-up program had not been objectively evaluated. METHODS: We retrospectively analyzed the first-year cohort of ADHF patients treated with UF from 10/1/2019 to 10/1/2020, which totaled 30 patients, utilizing the CHF Solutions Aquadex FlexFlow™ System with active UF rate titration. RESULTS: Baseline patient characteristics were similar to RCTs: mean age 63, 73% male; 27% female; 53% Caucasian; 47% African American; 77% had LVEF ≤ 40. The baseline mean serum creatinine (Cr) was 1.84 ±0.62 mg/dL, mean GFR of 36.95 ±9.60 ml/min. HF re-admission rates were not significantly different than prior studies (17.2% at 30 d, 23.3% at 60 d, but in our cohort, per patient HF re-admission rates were reduced significantly by 60 d (0.30 p = 0.017). CONCLUSION: Our analysis showed success with UF in mainstream setting with reproducible results of significant volume loss without adverse renal effect, mitigation of recurrent Hdmissions, and remarkable subjective clinical benefit.

First report of Cephalerous virescens causing Algal leaf spot of Averrhoa carambola in India.

Averrhoa carambola (Star fruit) is a drought resistant edible fruit belongs to family Oxalidaceae. It is native of Malaysia and further cultivation is extended to China, Southeast Asia, India and Northern South America. Star fruit has juicy texture and used in salads, beverages and traditionally it has been used for ayurvedic medicines in India, Brazil and China (Abduh et al. 2023). In early January 2023, we observed the symptoms of raised, more or less circular, orange to dark brown, velvet textured, scattered algal leaf spots (1-4 mm) on the upper surface of A. carambola leaves at College farm, Agricultural College, Aswaraopet (17.252039 latitude, 81.109573 longitude) (Supplementary Fig 1). The disease was observed in 2 hectare model orchard with incidence of 45% causing leaf defoliation and thereby reducing the yield and quality of fruits. Transverse section cutting of algal spots revealed the algal thalli at subcuticular region and causing necrosis of epidermal cells. Sporangiophores (n=20) raised from algal leaf spot were cylindrical, 4 to 5 celled, 200-450 µm long x 8-20 µm wide, and forming a head cell with suffultory cells and sporangia on the top. Sporangia (n=20) were spherical to elliptical, rusty brown and 17.5-29 µm long × 18-23.6 µm wide and the total number of sporangia produced by each sporangiophores varies from 1 to 6. Setae (n=20) were filamentous with three to six celled, 17.5-50 µm long × 2.5-7.5 µm wide (Supplementary Figure 2). In our collection, mature gametangia were not observed. Morphological characters were studied on 20 diseased leaf samples collected from randomly selected five plants. To isolate pathogen, fresh algal thalli (n=5) were scraped from host tissue, surface sterilized (70% alcohol (30 s), 1% sodium hypochlorite (30 s) and sterile distilled water (3 × 60 s), inoculated to trebouxia liquid media and incubated at 25 ± 2 °C with a 12 hours photoperiod for 72 hours (Vasconcelos et al. 2018). The resultant five algal filaments were subjected to PCR amplification. The primer pair PNS1/NS41 was used in a PCR to amplify a fragment of 18S rRNA (Davis and Kaur 2019). The 18S rRNA gene sequences of the algae were compared using the Basic Local Alignment Search Tool (BLAST; http://www.ncbi.nlm.nih.gov/Blast/Blast.cgi) showed that our partial sequence had 99.5% similarity to C. virescens (KM020142.1). Hence, it was classified as C. virescens and sequences was deposited in NCBI-GenBank with accession numbers (OR053653, OR243777, OR429406, OR429407 and OR243779). For proving pathogenicity, algal filaments obtained from trebouxia liquid media were inoculated to 6 months old healthy A. carambola plant. Pathogenicity test was negative and typical symptoms could not be produced even up to 150 days of inoculation. In previous studies also, due to difficulty with production of zoospores in synthetic media, Koch's postulates of C. virescens as a plant pathogen has not been demonstrated experimentally (Sunpapao et al. 2017; Sanahuja et al. 2018; Kumar et al. 2019). In the second experiment, zoosporangia spore suspension were prepared from small pieces of algal leaf spot tissue processed in a sterile pestle and mortar and filtered through sterile cheesecloth (Sunpapao et al. 2017). A total of five isolates of zoosporangia spore suspension (1 x 102 to 1 x 104/ml of water) was sprayed on healthy, surface sterilized leaves of A. carambola plants (n=5) until runoff with a handheld airpump sprayer and incubated in green house (T: 25 oC, H: 80%). During the experiment leaves were remain attached to plant (5 days old) and plants were 6 months old grown in plastic pots under controlled conditions. Two plants were inoculated with each isolate and three non inoculated control plants were included. Non inoculated controls were sprayed with sterile distilled water. The pathogenicity experiment was repeated. The initial symptoms were produced 60 days after inoculation and complete algal thalli was observed on 90 days after inoculation, control plants were without any symptoms upto 150 days. Reisolated algal thalli from symptomatic plants were morphologically similar to original algal thalli and molecularly identified as C. virescens (accession number OR067193 and OR243810). Red rust caused by C. virescens is a major algal disease in the world and causing severe leaf defoliation in various horticultural crops viz., Mangifera indica (Vasconcelos et al. 2018), Manilkara zapota (Sunpapao et al. 2017), Psidium guajava (Rajbongshi et al. 2022), Ziziphus mauritiana (Shareefa et al. 2022) and Anacardium occidentale (Dooh et al. 2022). The available literature suggest that, this is the first report of algal leaf spot on A. carambola caused by C. virescens in India. This report extends the range of known pathogens associated with A. carambola plant and serves as a basis for development and implementing disease management strategies.

Penile Nodule: What's Your Diagnosis?

Smegma pearls can cause diagnostic dilemmas for pediatricians who are unfamiliar with this condition leading to unnecessary investigations and referrals. Despite the common occurrence of smegma pearls in uncircumcised young boys, it is not often reported in the literature. Smegma is a normal secretion consisting of desquamated epithelial cells, fat, and protein. It has mixed bacterial flora with smegma bacillus in 50% of cases. Smegma itself is neither damaging nor irritating substance and as Howe has stated, it is not carcinogenic also. Smegma production and keratinization of cells facilitate the separation of the fused foreskin from the glans epithelium. we are presenting a case of a penile nodule in the shaft of the penis without any pain, bleeding, or discharge. The smegma content gives a yellowish color to the lump. Smegma pearls do not have any covering sac. When the smegma is covered in a well-formed epithelial wall, it is called a smegma cyst. Long-standing smegma collection can turn into a hard stone-like structure called Smegmolith due to chronic irritation and mineral accumulation. Treatment should include monitoring for resolution with parental reassurance. Smegma pearls are benign, and they spontaneously resolve over time. This case report intends to help pediatricians correctly identify this benign, yet not widely published in the literature condition and reassure the parents and patients to improve the patient care and avoid unnecessary tests and referrals.

Interaction of the Brain-Selective Sulfotransferase SULT4A1 with Other Cytosolic Sulfotransferases: Effects on Protein Expression and Function.

Sulfotransferase (SULT) 4A1 is a brain-selective sulfotransferase-like protein that has recently been shown to be essential for normal neuronal development in mice. In the present study, SULT4A1 was found to colocalize with SULT1A1/3 in human brain neurons. Using immunoprecipitation, SULT4A1 was shown to interact with both SULT1A1 and SULT1A3 when expressed in human cells. Mutation of the conserved dimerization motif located in the C terminus of the sulfotransferases prevented this interaction. Both ectopically expressed and endogenous SULT4A1 decreased SULT1A1/3 protein levels in neuronal cells, and this was also prevented by mutation of the dimerization motif. During differentiation of neuronal SH-SY5Y cells, there was a loss in SULT1A1/3 protein but an increase in SULT4A1 protein. This resulted in an increase in the toxicity of dopamine, a substrate for SULT1A3. Inhibition of SULT4A1 using small interference RNA abrogated the loss in SULT1A1/3 and reversed dopamine toxicity. These results show a reciprocal relationship between SULT4A1 and the other sulfotransferases, suggesting that it may act as a chaperone to control the expression of SULT1A1/3 in neuronal cells. SIGNIFICANCE STATEMENT: The catalytically inactive sulfotransferase (SULT) 4A1 may regulate the function of other SULTs by interacting with them via a conserved dimerization motif. In neuron-like cells, SULT4A1 is able to modulate dopamine toxicity by interacting with SULT1A3, potentially decreasing the metabolism of dopamine.

Health care providers' use of a drug information service for pregnancy-related inquiries.

OBJECTIVES: To characterize pregnancy and lactation-related medication inquiries to a drug information center to identify classes of medications of most concern to providers. A secondary objective was to identify any trends in provider inquiries over the study period. DESIGN: A retrospective descriptive study of pregnancy and lactation-related inquiries to the University of North Carolina Health Care System Drug Information Center database between January 2001 and December 2010. SETTING: University of North Carolina Health Care System Drug Information Center. INTERVENTION: Provider inquiries and responses were extracted and characterized by indication for treatment and reason for inquiry. Comparison of the first and second 5-year periods was performed to delineate trends. Descriptive statistics, Fisher's Exact and χ2 tests were used for analysis. MAIN OUTCOME MEASURES: Inquiry origin, time, and subject. RESULTS: 433 inquiries were retrieved over the study period from physicians (50%), pharmacists (21%), and nurses (18%). Inquiries were most often made during the antepartum period (34%), followed by the postpartum (28%) and preconception (22%) periods. The most frequent indications for inquiry were psychiatry (15%) and infectious diseases (14%), which remained constant throughout the study period. Safety was the most common reason for inquiry (52%). The responses provided to callers were limited due to lack of information availability 37% of the time. CONCLUSION: Psychiatry and infectious disease-related indications are the most frequent subjects of provider inquiry regarding medication use in pregnancy. Rates of inquiry remained constant throughout the past decade in most therapeutic areas. These findings are consistent with previous observations in other developed countries and suggest high-yield areas for pharmacist education.

Primary neuroendocrine carcinoma of male breast: A cytologically diagnosed rare entity.

Primary neuroendocrine (NE) carcinoma of the male breast is very rare. NE breast cancers encompass a heterogeneous group of tumors exhibiting morphological features similar to those of NE tumors of the gut and lung. They express one or more NE markers in at least 50% of the tumor cells. They are rare lesions representing about 2-3% of all breast cancers and more frequently affecting elderly patients. The present case report deals with a NE breast carcinoma in an 80-year-old male who presented with a right breast mass and axillary lymphadenopathy. The cytological features were suggestive of NE carcinoma. A thorough clinical evaluation helped confirm the primary nature of the tumor. The histopathology and immunohistochemistry helped confirm the cytological diagnosis. The histogenesis and prognostic implications of this rare breast tumor with predominant NE differentiation, unusually occurring in a male, is discussed here.

Expression of the orphan cytosolic sulfotransferase SULT4A1 and its major splice variant in human tissues and cells: dimerization, degradation and polyubiquitination.

The cytosolic sulfotransferase SULT4A1 is highly conserved between mammalian species but its function remains unknown. Polymorphisms in the SULT4A1 gene have been linked to susceptibility to schizophrenia. There are 2 major SULT4A1 transcripts in humans, one that encodes full length protein (wild-type) and one that encodes a truncated protein (variant). Here, we investigated the expression of SULT4A1 in human tissues by RT-PCR and found the wild-type mRNA to be expressed mainly in the brain, gastrointestinal tract and prostate while the splice variant was more widely expressed. In human cell-lines, the wild-type transcript was found in neuronal cells, but the variant transcript was expressed in nearly all other lines examined. Western blot analysis only identified SULT4A1 protein in cells that expressed the wild-type mRNA. No variant protein was detected in cells that expressed the variant mRNA. Ectopically expressed full length SULT4A1 protein was stable while the truncated protein was not, having a half-life of approximately 3 hr. SULT4A1 was also shown to homodimerize, consistent with other SULTs that contain the consensus dimerization motif. Mutation of the dimerization motif resulted in a monomeric form of SULT4A1 that was rapidly degraded by polyubiquitination on the lysine located within the dimerization motif. These results show that SULT4A1 is widely expressed in human tissues, but mostly as a splice variant that produces a rapidly degraded protein. Dimerization protects the protein from degradation. Since many other cytosolic sulfotransferases possess the conserved lysine within the dimerization motif, homodimerization may serve, in part, to stabilize these enzymes in vivo.

Cytosolic sulfotransferase 1A3 is induced by dopamine and protects neuronal cells from dopamine toxicity: role of D1 receptor-N-methyl-D-aspartate receptor coupling.

Dopamine neurotoxicity is associated with several neurodegenerative diseases, and neurons utilize several mechanisms, including uptake and metabolism, to protect them from injury. Metabolism of dopamine involves three enzymes: monoamine oxidase, catechol O-methyltransferase, and sulfotransferase. In primates but not lower order animals, a sulfotransferase (SULT1A3) is present that can rapidly metabolize dopamine to dopamine sulfate. Here, we show that SULT1A3 and a closely related protein SULT1A1 are highly inducible by dopamine. This involves activation of the D1 and NMDA receptors. Both ERK1/2 phosphorylation and calcineurin activation are required for induction. Pharmacological agents that inhibited induction or siRNA targeting SULT1A3 significantly increased the susceptibility of cells to dopamine toxicity. Taken together, these results show that dopamine can induce its own metabolism and protect neuron-like cells from damage, suggesting that SULT1A3 activity may be a risk factor for dopamine-dependent neurodegenerative diseases.

A pure epidural spinal cavernous hemangioma - with an innocuous face but a perilous behaviour!!

Cavernous hemangiomas occur frequently in the intracranial structures but they are rare in the spine, with an incidence of 0.22 cases/million/year, which account for 5 - 12% of the spinal vascular lesions, 51% of which are extradural. Most of the epidural hemangiomas are secondary extensions from the vertebral lesions. The spinal cavernous hemangiomas which do not involve the vertebrae are referred to as "pure" types. The pure epidural hemangiomas are rare, which account for only 4% of all the epidural lesions. A case of a Pure spinal epidural cavernous hemangioma in a 50 year old male, with the clinical picture of a slowly progressive compressive myelopathy, has been presented here. The imaging studies showed a well-defined, enhancing epidural lesion at the T7 - T8 level, with dorsal cordedema and myelomalacic changes. A radiological diagnosis of a meningioma was considered. Histopathologically, the lesion was diagnosed as a hemangioma. The patient improved dramatically after the excision of the lesion.

Effect of human telomerase reverse transcriptase transfection on differentiation in BeWo choriocarcinoma cells.

Arrest of proliferation is one of the prerequisites for differentiation of cytotrophoblasts into syncytiotrophoblasts, and thus during differentiation telomerase activity, as well as human telomerase reverse transcriptase (hTERT) expression, is down-regulated. Considering this, it is of interest to investigate whether syncytium formation can be delayed by prolonging the expression of telomerase in cytotrophoblasts. BeWo cells were transfected with pLPC-hTERT retroviral vector and the reverse transcription-polymerase chain reaction analysis for hTERT mRNA concentrations in the transfected cells revealed a several-fold increase in hTERT mRNA compared with the cells transfected with empty vector, and this confirmed that the transfection was successful. An increase in the proliferation, as assessed by bromodeoxyuridine incorporation assay, as well as an increase in mRNA and protein concentration of various cyclins and proliferating cell nuclear antigen, was noticed. The effect of hTERT transfection was also assessed after the addition of forskolin to induce differentiation and it was observed that cell-cell fusion was delayed and differentiation did not occur in hTERT-transfected cells. However, the effects seen were only transient as stable transfection was not possible and the cells were undergoing apoptosis after 72 h, which suggested that apart from hTERT other factors might be important for immortalization of BeWo cells.

Gene expression profiling during Forskolin induced differentiation of BeWo cells by differential display RT-PCR.

The differentiation of cytotrophoblasts into syncytiotrophoblasts in the placenta has been employed as a model to investigate stage specific expression as well as regulation of genes during this process. While the cytotrophoblasts are highly invasive and proliferative with relatively less capacity to synthesize pregnancy related proteins, the multinucleated syncytiotrophoblasts are non-proliferative and non-invasive. However, syncytiotrophoblasts are the site of synthesis of a variety of protein, peptide and steroid hormones as well as several growth factors. Both the freshly isolated cytotrophoblasts from human placenta as well as the BeWo cell, a choriocarcinoma cell line model which retain several characteristic of cytotrophoblasts has been employed by us to study regulation of differentiation. In the present study, we have employed the differential display RT-PCR analysis (DD-RT-PCR) to evaluate gene expression changes during Forskolin induced in vitro differentiation of BeWo cells. We have identified several genes which are differentially expressed during differentiation and the differential expression of 10 transcripts was confirmed by Northern blot analysis. Based on the identity of the transcripts an attempt has been made to relate the known function of the gene products, to changes observed during differentiation. Of the several transcripts, one of the transcripts, namely Secretory Leukocyte Protease Inhibitor (SLPI) which is known to have multiple functions was found to increase 15-fold in the syntiotrophoblast.

Proteomic profiling of forskolin-induced differentiated BeWo cells: an in-vitro model of cytotrophoblast differentiation.

Placental trophoblastic differentiation is characterized by the fusion of monolayer cytotrophoblasts into syncytiotrophoblasts. During this process of differentiation, several morphological and biochemical changes are known to occur, and this model has been employed to investigate the changes that occur at the gene and protein level during differentiation. Using the sensitive technique of proteomics [two-dimensional gel electrophoresis (2DGE)], changes in protein profile were evaluated in the control and forskolin-induced differentiated cells of trophoblastic choriocarcinoma BeWo cell line. Several proteins were differentially expressed in control and differentiated cells. Four major proteins were up-regulated as assessed by silver staining, and were further characterized as c-h-ras p 21 (phosphorylated), retinoblastoma susceptibility protein 1 and integrase interactor protein 1. These proteins are known to play an important role in growth arrest of cells, and thus may play a role in initiating the process of differentiation.

Differential effect of cadmium and mercury on growth and metabolism of Solanum melongena L. seedlings.

The present investigation reports the results of the effect of cadmium and mercury individually on seed germination, seedling growth, number of lateral roots, fresh and dry weights and seedling metabolism in Solanum melongena. Effect of different concentrations of these two heavy metals (Cadmium--50, 100, 300, 500, 700, 1000, 3000, 5000, 7000 and 9000 ppm and Mercury--5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 ppm) and durations for 6, 12 and 24 h were employed for all seedling parameters of brinjal. Both Cd and Hg showed drastic effects at high concentrations and longer duration with regard to seedling growth and metabolism.