Efficacy of optimal nutraceutical combination in treating PCOS characteristics: an in-silico assessment.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a serious health condition affecting women of reproductive age. High prevalence of PCOS and associated metabolic complications needs effective treatment and management. This study evaluated the efficacy of optimal nutraceutical combinations in improving PCOS characteristics using system biology-based mathematical modelling and simulation. METHODS: A shortlisting of eight potent nutraceuticals was carried out with literature search. Menstrual cycle model was used to perform simulations on an in-silico population of 2000 individuals to test individual and combined effects of shortlisted nutraceuticals on five PCOS characteristics [oligomenorrhea, anovulation, hirsutism, infertility, and polycystic ovarian morphology (PCOM)] for a duration of 6 months. Efficacy was tested across lean and obese phenotypes and age groups. RESULTS: Individual assessment of nutraceuticals revealed seven most potent compounds. Myo-inositol among them was observed to be the most effective in alleviating the PCOS characteristics. The in-silico population analysis showed that the combination of melatonin and ALA along with myo-inositol was efficacious in restoring the hormonal balance across age-groups and Body Mass Index (BMI) categories. CONCLUSION: Supplementation with the combination of myo-inositol, melatonin, and ALA demonstrated potential in managing PCOS symptoms in our in-silico analysis of a heterogeneous population, including lean and obese phenotypes across various severities and age groups, over a 6-month period. Future clinical studies are recommended to validate these findings.

Analytics Pipeline for Visualization of Single Cell RNA Sequencing Data from Brochoaveolar Fluid in COVID-19 Patients: Assessment of Neuro Fuzzy-C-Means and HDBSCAN.

Since the mutation in SARS-COV2 poses new challenges in designing vaccines, it is imperative to develop advanced tools for visualizing the genetic information. Specially, it remains challenging to address the patient-to-patient variability and identify the signature for severe/critical conditions. In this endeavor we analyze the large-scale RNA-sequencing data collected from broncho-alveolar fluid. In this work, we have used PCA and tSNE for the dimension-reduction. The novelty of the current work is to depict a detailed comparison of k-means, HDBSAN and neuro-fuzzy method in visualization of high-dimension data on gene expression. Clinical Relevance- The subpopulation profiling can be used to study the patient-to patient variability when infected by SARS-COV-2 and its variants. The distribution of cell types can be relevant in designing new drugs that are targeted to control the distribution of epithelial cells T cells and macrophages.

Effect of Onconase on double-stranded RNA in vitro.

Onconase is a cytotoxic ribonuclease which targets tumor cells in vivo and in vitro. To date, cellular tRNA appeared to be the major target for Onconase mediated cytotoxic activity. Most recently we demonstrated that Onconase can also cleave double-stranded RNA (dsRNA). Incubation of Onconase at 37 degrees C with GAPDH gene-dsRNA (approximately 440 bp long) and dsRNA ladder showed degradation of dsRNA into a spectrum of smaller dsRNA fragments. Moreover, incubation of dsRNA substrates at 40 degrees C under similar conditions markedly potentiated further cleavage of dsRNAs. The recently discovered double-stranded RNase activity of Onconase suggests another mechanism for inducing cell death/apoptosis in malignant phenotypes via the RNA interference mechanism involving siRNA and miRNA.

Enzymatic and structural characterisation of amphinase, a novel cytotoxic ribonuclease from Rana pipiens oocytes.

Besides Onconase (ONC) and its V11/N20/R103-variant, oocytes of the Northern Leopard frog (Rana pipiens) contain another homologue of ribonuclease A, which we named Amphinase (Amph). Four variants (Amph-1-4) were isolated and sequenced, each 114 amino acid residues in length and N-glycosylated at two positions. Sequence identities (a) among the variants and (b) versus ONC are 86.8-99.1% and 38.2-40.0%, respectively. When compared with other amphibian ribonucleases, a typical pattern of cysteine residues is evident but the N-terminal pyroglutamate residue is replaced by a six-residue extension. Amph variants have relatively weak ribonucleolytic activity that is insensitive to human ribonuclease inhibitor protein (RI). Values of k(cat)/K(M) with hypersensitive fluorogenic substrates are 10(4) and 10(2)-fold lower than the maximum values exhibited by ribonuclease A and ONC, respectively, and there is little cytosine/uracil or adenine/guanine discrimination at the B(1) or B(2) subsites, respectively. Amph variants have cytotoxic activity toward A-253 carcinoma cells that requires intact ribonucleolytic activity. The glycan component has little or no influence over single-stranded RNA cleavage, RI evasion or cytotoxicity. The crystal structures of natural and recombinant Amph-2 (determined at 1.8 and 1.9 A resolution, respectively) reveal that the N terminus is unlikely to play a catalytic role (but an unusual alpha2-beta1 loop may do so) and the B(2) subsite is rudimentary. At the active site, structural features that may contribute to the enzyme's low ribonucleolytic activity are the fixture of Lys14 in an obstructive position, the accompanying ejection of Lys42, and a lack of constraints on the conformations of Lys42 and His107.

Propofol for pediatric radiotherapy.

OBJECTIVE: Pediatric radiotherapy is a day care procedure. In children, anaesthesia is necessary to prevent movement during the therapy. Traditionally intramuscular ketamine is used for these procedure because of its inherent safety in a child who used to be left alone in the cobalt room. METHODS: This study was designed to explore the efficacy of propofol and ketamine in pediatric radiotherapy in nineteen children. The inclusion criteria was a child fasting for six hours with no fever or URTI in the past week. A child coming to the radiotherapy (RT) unit without an intravenous cannula was given intramuscular ketamine 10 mg/kg and taken for the procedure. Before the child recovered from anaesthesia an intravenous cannula, 20-22G, Vasofix was inserted for subsequent sittings of RT. The child coming with an intravenous cannula was given propofol 2.5 mg/kg with xylocaine (0.1 mg/kg) without adrenaline. The parameters recorded were pulse rate, oxygen saturation and respiratory rate-baseline to every 30 seconds till five minutes. Onset time, recovery time, oral feeding time and any untoward effects like nausea, vomiting, nystagmus were also noted. RESULT: The drug was graded on a scale of 0-10 according to parental acceptability where 0 is the worst and 10 is the best acceptability. The mean (+/-SD) of all the measured parameters were calculated and compared between the two groups. CONCLUSION: Propofol was associated with faster onset, better recovery, early oral feeding time, no nausea and vomiting and better parental acceptability. There was no hypotension, bradycardia and oxygen saturation at 60 seconds, which was between 94-95%, was easily treatable with supplementation of oxygen by face mask.

Oral ketamine as an adjuvant to oral morphine for neuropathic pain in cancer patients.

To evaluate the role of oral ketamine as an adjuvant to oral morphine in cancer patients experiencing neuropathic pain, 9 cancer patients (5 men, 4 women) taking maximally tolerated doses of either morphine, amitriptyline, sodium valproate, or a combination of these drugs for intractable neuropathic pain, and reporting a pain score of >6 on a 0-10 scale, were studied prospectively to evaluate analgesia and adverse effects. Ketamine in the dose of 0.5 mg/kg body weight three times daily was added to the existing drug regimen. Patients were taught to maintain a pain diary wherein they daily recorded their pain, sedation, and vomiting scores, and other side effects. A decrease of more than 3 from the baseline in the average pain score, or a score of < or =3 was taken as a successful response. Seven patients exhibited a decrease of more than 3. Four patients experienced nausea, of which one had vomiting. Two developed loss of appetite. Eight patients reported drowsiness during the first two weeks of therapy (P = 0.001), and this gradually improved over the next two weeks in 5 of these 8 patients. Three patients withdrew from the study, two owing to excessive sedation and another due to a "feeling of unreality." None of the patients reported visual or auditory hallucinations. This experience suggests that low dose oral ketamine is beneficial and effective in the management of intractable neuropathic pain in patients with advanced cancer. However, its utility is limited in some patients by the adverse effects that accompany its use.