Prevalence of vitamin D deficiency among patients attending Post COVID-19 follow-up clinic: a cross-sectional study.

OBJECTIVE: Post-COVID-19 syndrome appears to be a multi-organ illness with a broad spectrum of manifestations, occurring after even mild acute illness. Limited data currently available has suggested that vitamin D deficiency may play a role in COVID-19 cases. However, to our knowledge, no study has examined the frequency of vitamin D deficiency in post-COVID-19 cases and its effect on the symptom severity. The aim of this study is to both screen the frequency of vitamin D deficiency in post-COVID-19 syndrome patients and to study its relation to persistent symptoms. PATIENTS AND METHODS: A cross-sectional, single-center study was conducted involving all cases attending post-COVID-19 follow-up clinic from November 2020 to May 2021. Complete history, clinical examination, and laboratory analysis [kidney functions, serum calcium, C-reactive protein, serum ferritin, Serum 25-(OH) vitamin D] was done as well as HRCT chest. RESULTS: The study included 219 post-COVID-19 cases, 84% had deficient vitamin D levels (< 20 ng/dL); 11.4% had insufficient level (20-30 ng/dL) and only 4.9 % reported normal level. There was no link between levels of vitamin D with either the acute or post-COVID-19 symptoms in the studied groups. CONCLUSIONS: Despite the prevalence of vitamin D deficiency among the study population, no association was observed between the levels of vitamin D and post-COVID-19 symptoms. It appears that post-COVID-19 syndrome pathophysiology involves a more complex interaction with the immune system. Dedicated clinical trials are advised to better study vitamin D levels and the related disease severity in COVID-19 patients.

Diadema setosum: isolation of bioactive secondary metabolites with cytotoxic activity toward human cervical cancer.

In our promising project toward discovery of secondary metabolites with potential anticancer activity against human cervical cancer, seven marine organisms were screened for their cytotoxic activity against HeLa cancer cell line using MTT colorimetric assay. The crude extract of the outer shell of Diadema setosum showed promising activity with 88.02% inhibition at a concentration 250 µg/ml. Chromatographic investigation of the Ethyl acetate fraction, which is the main contributor to the activity (IC50= 43.1 ± 5.94 µg/ml), led to isolation of five compounds. Structures of the isolates (1-5) were elucidated by 1 D and 2 D NMR spectroscopy and HR-ESI-MS analysis. 5α,8α-epidioxycholest-6-en-3ß ol (2) and 5α,8α-epidioxycholest-6,9(11)-en-3ß ol (3) showed the highest cytotoxic activity with IC50 values 12.1 ± 2.74 µg/ml and 21.8 ± 6.32 µg/ml, respectively. Epidioxy steroids with cholestane nucleus could be a prospective candidate for the development of drugs for treatment of human cervical cancer.

Two new polyhydroxylated steroids from Egyptian soft coral Heteroxenia fuscescens (Fam.; Xeniidae).

Two new polyhydroxylated steroids, 3ß-acetoxy-gorgost-5α,6ß,11α-triol (3) and (23 R) methylergosta-20-ene-3ß,5α,6ß,17α-tetrol (4), together with three known gorgosteroid compounds, gorgost-3ß, 5α,6ß,11α- tetrol (1), 11α-acetoxy-gorgost- 3ß,5α, 6ß- triol (2), and gorgost-5 (E) ene-3-ß-ol (5), as well as batyl alcohol (6), were isolated from the Egyptian soft coral Heteroxenia fuscescens. The structures of these compounds were elucidated based on NMR spectroscopic analyses, HR-FAB-MS, and comparisons with published data. The cytotoxic activities of the fractions and compounds were evaluated against MCF-7 cancer cell lines using MTT colorimetric assay. Compounds 2 and 4 showed moderate cytotoxic activity, with IC50 values equal to 33.2 and 25.1 µM, respectively, in comparison with the IC50 of 5-fluorouracil 18.7 µM.

Recurrent takotsubo with prolonged QT and torsade de pointes and left ventricular thrombus.

Takotsubo cardiomyopathy, also known as "takotsubo syndrome," refers to transient apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome and is a recently recognized syndrome typically characterized by transient and reversible left ventricular dysfunction that develops in the setting of acute severe emotional or physical stress. Increased catecholamine levels have been proposed to play a central role in the pathogenesis of the disease, although the specific pathophysiology of this condition remains to be fully determined. At present, there have been very few reports of recurrent takotsubo cardiomyopathy. In this case report, we present a patient with multiple recurrences of takotsubo syndrome triggered by severe emotional stress that presented with recurrent loss of consciousness, QT prolongation, and polymorphic ventricular tachycardia (torsade de pointes) and left ventricular apical thrombus.

PIVKA-II correlates with INR but not protein C or protein S concentrations in cord blood among newborns.

BACKGROUND: Protein induced by vitamin K absence (PIVKA)-II, inactive precursor of prothrombin, is elevated in vitamin K (VK) deficiency. Our aims were to find the prevalence of VK deficiency in neonates, assess the utility of international normalized ratio (INR) as a screening tool, and explore the relationship between PIVKA-II, activated partial thromboplastin time (aPTT) and VK dependent anticoagulants. METHODS: INR, aPTT, PIVKA-II, and proteins C and S activities were measured in neonatal cord blood prior to VK administration. RESULTS: We found 45% of neonates had subclinical VK deficiency based on PIVKA-II levels and 7% based on INR. Receiver operating characteristic (ROC) analysis assessed the utility of INR in detecting >4 ng/mL of PIVKA-II and ROC of the area under the curve was 0.70 (95% CI 0.46-0.92, p = 0.07). Proteins C and S activities were normal for age and did not correlate with PIVKA-II [(r = 0.40, p = 0.14) and (r = 0.29, p = 0.29), respectively]. There was no association between aPTT and PIVKA-II (p = 0.83). CONCLUSION: PIVKA-II seems to be a sensitive indicator of mild VK deficiency. Further studies are needed to investigate the lack of relationship between PIVKA-II and functional protein C or S levels.

BMP-specific SMADs function as novel repressors of PDGFA and modulate its expression in ovarian granulosa cells and tumors.

Platelet-derived growth factor alpha (PDGFA) is frequently upregulated in various cancers and thought to function as a key player in the development and progression of tumor growth by regulating aspects of cell proliferation, angiogenesis and metastasis. However, the mechanism by which it is upregulated is not fully understood. Previously, we demonstrated that conditional deletion of two transcription factors that signal for the bone morphogenetic proteins (Smad1 and Smad5) in ovarian granulosa cells causes metastatic granulosa cell tumors (GCTs) in female mice and phenocopies human juvenile GCTs (JGCTs). Smad1/5 double conditional knockout tumors, as well as human JGCTs, are highly vascularized, hemorrhagic and mitotically active. Expression analysis of these tumors and their metastases revealed a significant upregulation of key proliferation and pro-angiogenic factors such as Pdgfa, Pdgfb and Vegf. We examined whether these genes were direct targets of SMAD1 and SMAD5. Knockdown of SMAD1 and SMAD5 in mouse primary granulosa cells and a human GCT-derived cell line (COV434) resulted in upregulation of PDGFA, but not PDGFB nor VEGF. We identified several putative SMAD1/5-binding sites in the PDGFA promoter, and chromatin immunoprecipitation and reporter assays demonstrated that SMAD1/5 interact with the PDGFA promoter to regulate its activity. Further, SMAD1/5 antagonize the activity of the transcription factor Sp1, a well-known positive regulator of PDGFA, by inhibiting its occupancy at a key regulatory site on the proximal PDGFA promoter. Collectively, our studies establish that loss of SMAD1/5 leads to upregulation of PDGFA in ovarian granulosa cells, and that a novel regulatory interaction exists between the BR-SMADs and Sp1 in controlling PDGFA expression during granulosa cell tumorigenesis.

Fatal Epstein-Barr virus meningitis: an autopsy report.

A 3-year-old Asian female presented with fever for 1 week and neck swelling for 1 day. Serology revealed a recent Epstein-Barr virus (EBV) infection. Late on the evening of admission, she developed confusion and would not follow commands. A CT scan showed diffuse cerebral edema and a cerebral flow scan demonstrated no blood flow to the brain. She was declared brain dead and expired on the following day. At autopsy, the brain weighted 1175 grams and grossly showed significant edema. Microscopically, the entire neuraxis revealed extensive leptomeningeal infiltrate of mainly CD8+ T lymphocytes, the majority of which expressed activated markers, HLA-DR and/or CD45RO, and monocytes/macrophages with intermixed numerous apoptotic/karyorrhectic nuclear fragments. These nuclear fragments were considered to be due to apoptosis of the expanded population of CD8+ T lymphocytes. Focal venulitis was noted. EBV-encoded small nuclear RNA in situ hybridization revealed positivity in the occasional lymphocytes. Interestingly, most intraparenchymal as well as leptomeningeal vascular endothelium showed HLA-DR immunoreactivity. This finding has been reported primarily in the acute inflammatory/demyelinating conditions, not in the viral meningitis/meningoencephalitis, and was thought to be related to cytokines due to widespread inflammation in our case. Massive edema secondary to severe EBV-meningitis can be fatal.

MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive multisystem disorder caused by thymidine phosphorylase (TP) deficiency, resulting in severe gastrointestinal dysmotility and skeletal muscle abnormalities. A patient is reported with a classical MNGIE clinical presentation but without skeletal muscle involvement at morphological, enzymatic, or mitochondrial DNA level, though gastrointestinal myopathy was present. MNGIE was diagnosed by markedly raised plasma thymidine and reduced thymidine phosphorylase activity. Molecular genetic analysis showed a homozygous novel splice site mutation in TP. On immunohistochemical studies there was marked TP expression in the CNS, in contrast to what has been observed in rodents. It is important to examine the most significantly affected tissue and to measure TP activity and plasma thymidine in order to arrive at an accurate diagnosis in this condition.