Prospective Study to Evaluate Efficacy of Single Versus Double Drains in Breast Cancer Patients Undergoing Surgery.

Seroma formation is a common sequel following modified radical mastectomy (MRM), which hinders healing, may prolong hospital stay, and cause a delay in adjuvant treatment. Closed suction drains have been used to prevent formation of seroma; however, the use of a single drain in the axilla along with draining the mastectomy flaps and axilla separately remains a topic of debate. This prospective randomized dual-arm study was conducted in the Department of Endocrine Surgery. All female patients with carcinoma breast diagnosed on core tissue biopsy, undergoing modified radical mastectomy, upfront or post neoadjuvant systemic therapy were included. Patients were randomized into two groups. In the first group, a single drain was placed in the axilla whereas in the second group, a drain each was placed below the mastectomy flaps and the axilla. Patients' particulars and the weight of the mass excised along with the operative details were documented. The volume of the drain was recorded daily. The flap drain was removed on postoperative day 5 and the axillary drain was removed when the drain volume was less than 30 mL/24 h for 2 consecutive days. The period of drain placement, volume of drainage, volume of seroma (if formed), and other complications (if any) were recorded. Patients in the single drain group had a significantly earlier drain removal time as compared to those with double drains (p = 0.01). The number of patients in whom seroma formation had occurred was more in the double drain group, but the difference was not significant. The average volume of aspirated seroma fluid was insignificantly more in the single drain group. The only other complication noticed was flap necrosis-in 5% patients of the double drain group. Total volume of drainage (p < 0.0001) and type of drain (p = 0.0208) were associated with higher rates of seroma formation, whereas BMI (p = 0.0516), weight of excised breast mass (p = 0.407), and age (p = 0.6379) were not associated with the rate of seroma formation. Outcomes in terms of drain volume or seroma formation were statistically indifferent between the two groups. Still, use of only a single axillary drain should be promoted, keeping in mind the earlier drain removal period, better patient compliance, and reduced hospital stay.

U.S. public perceptions of the sensitivity of brain data.

As we approach an era of potentially widespread consumer neurotechnology, scholars and organizations worldwide have started to raise concerns about the data privacy issues these devices will present. Notably absent in these discussions is empirical evidence about how the public perceives that same information. This article presents the results of a nationwide survey on public perceptions of brain data, to inform discussions of law and policy regarding brain data governance. The survey reveals that the public may perceive certain brain data as less sensitive than other 'private' information, like social security numbers, but more sensitive than some 'public' information, like media preferences. The findings also reveal that not all inferences about mental experiences may be perceived as equally sensitive, and perhaps not all data should be treated alike in ethical and policy discussions. An enhanced understanding of public perceptions of brain data could advance the development of ethical and legal norms concerning consumer neurotechnology.

Hypothyroidism in acute coronary syndrome - A prospective Indian study.

BACKGROUND: Evidence suggests that hypothyroidism may be associated with an increased risk of acute coronary syndrome (ACS). The data regarding the influence of hypothyroidism on cardiovascular disease in the Asian population is conflicting. Therefore, we undertook this study to assess the overall prevalence of hypothyroidism in Acute Coronary Syndrome (ACS) patients and determine if there is a relationship between hypothyroidism, both sub-clinical and overt and other significant risk factors of ACS in an Indian population. METHODS: We studied 487 hospitalized patients between March 2018 and February 2021 with a diagnosis of ACS to determine the prevalence of hypothyroidism, both clinical and sub-clinical and their relationship with other known coronary risk factors. Thyroid function Tests - free T3, free T4 and TSH were collected from all the patients within 24 h of their admission to the coronary care unit (CCU) of 2 major hospitals in New Delhi and Imphal (Manipur). RESULTS: Subclinical hypothyroidism was prevalent in 44 (9 %), followed by overt hypothyroidism in 25 (5.2 %). Subclinical hypothyroidism was more common in females, whereas overt hypothyroidism was more common in males. ST Elevation Myocardial Infarction (STEMI) (52 %), followed by Non-ST-Elevation Myocardial Infarction (NSTEMI) (25 %), was the commonest diagnosis at presentation. Patients with overt hypothyroidism showed a higher proportion of increased triglyceride levels. Patients with hypothyroidism had no differences in the prevalence of concomitant diabetes hypertension and other coronary risk factors. CONCLUSIONS: Patients with ACS without known thyroid disorders should be screened for hypothyroidism since it is found frequently. There might be a case to treat their thyroid dysfunction appropriately.

Intracranial Microhemorrhages in a Patient With Tubercular Meningitis (TBM): A Case Report.

Intracranial tuberculosis (TB) is the most serious form of systemic TB and constitutes an important cause of morbidity and mortality in underdeveloped countries. Central nervous system TB is a difficult diagnosis to make, and treat, especially in the developing nations. Intracranial hemorrhage is one of the rare complications of intracranial TB. We are reporting a case of a 70-year-old male patient who presented to the neurology ward with complaints of persistent high-grade fever associated with significant weight loss, night sweats, and hemolysis for two months. Cerebrospinal fluid analysis was suggestive of tubercular meningitis. He was started on first-line antitubercular therapy. After two weeks, he developed respiratory distress, and invasive mechanical ventilation was started. He was then referred to the Intensive Care Unit of the Critical Care Medicine department. Susceptibility weighted images magnetic resonance imaging (MRI) revealed multiple nodular and ring-enhancing lesions with multifocal areas of microhemorrhages in the brain parenchyma, and leptomeningeal enhancement in bilateral sylvian, perimesencephalic, prepontine and cerebellopontine angles. A tracheostomy was performed. He also developed septic shock for 72 hours, secondary to Pseudomonas aeruginosa and Acinetobacter baumannii ventilator-associated pneumonia, and Klebsiella bacteremia for which intravenous noradrenalin, Carbapenem and Colistin were administered. The patient improved within eight weeks. Our case presented with altered sensorium for the past three to four days but generally, there are other common features like headache, seizures, focal neurological deficit, and raised intracranial pressure. MRI findings of caseating tuberculomas reveal isointense to hypointense signals on both T2 and T1 weighted images with ring enhancement, which are in resemblance with the MRI findings of our case.

Biomimetic Stratum Corneum Liposome Models: Lamellar Organization and Permeability Studies.

The stratum corneum (SC), the outer layer of the skin, plays a crucial role as a barrier protecting the underlying cells from external stress. The SC comprises three key components: ceramide (CER), free fatty acid (FFA), and cholesterol, along with small fractions of cholesterol sulfate and cholesterol ester. In order to gain a deeper understanding about the interdependence of the two major components, CER and FFA, on the organizational, structural, and functional properties of the SC layer, a library of SC lipid liposome (SCLL) models was developed by mixing CER (phytosphingosine or sphingosine), FFA (oleic acid, palmitic acid, or stearic acid), cholesterol, and cholesterol sulfate. Self-assembly of the SC lipids into lamellar phases was first confirmed by small-angle X-ray scattering. Short periodicity and long periodicity phases were identified for SCLLs containing phytosphingosines and sphingosine CERs, respectively. Furthermore, unsaturation in the CER acyl and FFA chains reduced the lipid conformational ordering and packing density of the liposomal bilayer, which were measured by differential scanning calorimetry and Fourier transform infrared spectroscopy. The introduction of unsaturation in the CER and/or FFA chains also impacted the lamellar integrity and permeability. This extensive library of SCLL models exhibiting physiologically relevant lamellar phases with defined structural and functional properties may potentially be used as a model system for screening pharmaceuticals or cosmetic agents.

Expanded Dengue Syndrome Presenting as Intracranial Hemorrhage, Fever, and Rhabdomyolysis: A Case Report.

Rare clinical manifestations of dengue are included under the expanded dengue syndrome (EDS), with intracranial hemorrhage (ICH) being one of them. We discuss an uncommon presentation of dengue with basal ganglia hemorrhage, hyperthermia, and rhabdomyolysis in a 53-year-old hypertensive female who presented with sudden onset syncope, left-sided weakness, and altered sensorium for days, with high-grade fever and vomiting. The Glasgow coma scale (GCS) score was 5, and the patient was intubated. Noncontrast computerized tomography (NCCT) of the brain revealed right basal ganglia bleeding with intraventricular hemorrhage. Electrocardiography (ECG) revealed sinus tachycardia. The patient had spikes of high-grade fever, rhabdomyolysis, stage III acute kidney disease, and coagulopathy. Dengue IgM antibodies were positive. Treatment was started, and the patient was in the intensive care unit (ICU) for six months, following which she was discharged. Given this, one can speculate on the importance of viral diseases presenting with ICH as these are rare and are diagnosed quite late, which can also prove to be fatal.

Dual binding site and selective acetylcholinesterase inhibitors derived from integrated pharmacophore models and sequential virtual screening.

In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer's randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

Antiobesity and lipid lowering effects of Glycyrrhiza chalcones: experimental and computational studies.

Twelve flavonoids (1-12), isolated from Glycyrrhiza glabra roots were evaluated for their pancreatic lipase (PL) inhibitory activity in vitro. The structures of the isolated compounds were elucidated by spectroscopic methods. Amongst all the compounds 7, 8, 10 and 11 showed strong inhibition against PL with IC(50) values of 7.3 µM, 35.5 µM, 14.9 µM and 37.6 µM, respectively. Molecular docking studies on the most active compound 7 revealed that it binds with the key amino acid residues of the PL active site. In silico absorption, distribution, metabolism and excretion (ADME) parameters were also computed on the active compounds to determine their preliminary pharmacokinetic properties. Further, investigations were carried out to determine the antiobesity and lipid lowering effects of 7 and 10 in high fat diet (HFD) fed male SD rats. In the rats supplemented with compound 7 the body weight increase was only 23.2±3.6 g as compared to 64.2±0.5 g in the HFD control group while in the rats treated with compound 10 showed 23.2±3.6 g weight gain only. Compound 7 decreased the levels of plasma total cholesterol (TC) to 84.6±1.4 mg/dl and plasma total triglycerides (TG) to 128.8±6.0 mg/dl. Compound 10 also lowered the plasma TC and TG levels considerably. The results indicate the potential of the chalcone scaffold as a source of PL inhibitors for preventing obesity.

Discovery of dual binding site acetylcholinesterase inhibitors identified by pharmacophore modeling and sequential virtual screening techniques.

Dual binding site acetylcholinesterase (AChE) inhibitors are promising for the treatment of Alzheimer's disease (AD). They alleviate the cognitive deficits and AD-modifying agents, by inhibiting the ß-amyloid (Aß) peptide aggregation, through binding to both the catalytic and peripheral anionic sites, the so called dual binding site of the AChE enzyme. In this Letter, chemical features based 3D-pharmacophore models were developed based on the eight potent and structurally diverse AChE inhibitors (I-VIII) obtained from high-throughput in vitro screening technique. The best 3D-pharmacophore model, Hypo1, consists of two hydrogen-bond acceptor lipid, one hydrophobe, and two hydrophobic aliphatic features obtained by Catalyst/HIPHOP algorithm adopted in Discovery studio program. Hypo1 was used as a 3D query in sequential virtual screening study to filter three small compound databases. Further, a total of nine compounds were selected and followed on in vitro analysis. Finally, we identified two leads--Specs1 (IC(50)=3.279 µM) and Spec2 (IC(50)=5.986 µM) dual binding site compounds from Specs database, having good AChE enzyme inhibitory activity.

Molecular Docking Guided Comparative GFA, G/PLS, SVM and ANN Models of Structurally Diverse Dual Binding Site Acetylcholinesterase Inhibitors.

Recently discovered 42 AChE inhibitors binding at the catalytic and peripheral anionic site were identified on the basis of molecular docking approach, and its comparative quantitative structure-activity relationship (QSAR) models were developed. These structurally diverse inhibitors were obtained by our previously reported high-throughput in vitro screening technique using 384-well plate's assay based on colorimetric method of Ellman. QSAR models were developed using (i) genetic function algorithm, (ii) genetic partial least squares, (iii) support vector machine and (iv) artificial neural network techniques. The QSAR model robustness and significance was critically assessed using different cross-validation techniques on test data set. The generated QSAR models using thermodynamic, electrotopological and electronic descriptors showed that nonlinear methods are more robust than linear methods, and provide insight into the structural features of compounds that are important for AChE inhibition.

Miniaturization and validation of the Ellman's reaction based acetylcholinesterase inhibitory assay into 384-well plate format and screening of a chemical library.

The aim of this study was to screen for acetylcholinesterase (AChE) inhibitors from a large chemical library of commercially available compounds. For this purpose, the Ellman's reaction based assay was miniaturized into 384-well plate format, and two modifications of the kinetic protocol were studied with the aim of developing a rapid screening platform that could ensure high efficiency in finding true hits. It was proven that when starting the kinetic reaction by addition of the substrate, better assay performance was achieved and more practical benefits obtained. Using the optimized automated protocol, a chemical library of 56,320 compounds was screened. A total of 350 positive hits were identified and their IC50 calculated. Three highly active compounds were identified with IC50 values close or even lower to physostigmine (< 0.1 microM). The activity towards butyrylcholinesterase (BChE) of these three most active hits was also evaluated. The most active hit (IC(50(AChE)) = 0.019 microM), was identified as a new inhibitor, belonging to ChemDiv chemical library: (N-[3-(3,5-dimethyl-1-piperidinyl)propyl]-5-ethyl-2-methyl-8-oxo-thieno[2',3':4,5]pyrrolo[1,2-d] [1,2,4] triazine-7(8H)-acetamid), with no other biological activities reported until now. The interactions of this hit with both cholinesterases were further analyzed using computational docking studies. To our knowledge, this is the largest published screening campaign of commercially available compounds that has focused on finding new AChE inhibitors. The miniaturized 384-well plate format of the Ellman's method was proven to be robust and to perform reliably.

Ligand-based molecular design of 4-benzylpiperidinealkylureas and amides as CCR3 antagonists.

Asthma is an inflammatory disease of the lungs. Clinical studies suggest that eotaxin and chemokine receptor-3 (CCR3) play a primary role in the recruitment of eosinophils in allergic asthma. Development of novel and potent CCR3 antagonists could provide a novel mechanism for inhibition of this recruitment process, thereby preventing asthma. With the intention of designing new ligands with enhanced inhibitor potencies against CCR3, a 3D-QSAR CoMFA study was carried out on 41 4-benzylpiperidinealkylureas and amide derivatives. The best statistics of the developed CoMFA model were r (2) = 0.960, r(2)cv, n = 32 for the training set and r(2)pred, n = 9 for the test set. The generated 3D-QSAR contribution maps shed some light on the effects of the substitution pattern related to CCR3 antagonist activity.

Inhibition of acetylcholinesterase by coumarins: the case of coumarin 106.

In this contribution, from a coumarin library consisting of 29 compounds including natural and synthetic derivatives, an active acetylcholinesterase (AChE) inhibitor (coumarin 106) was found. This circumstance leaded us to continue with the pharmacological characterization of coumarin 106. The first study with the coumarin library was performed using a 96-microtiter well plate assay based on Ellman's reaction. Coumarins were assayed at 5 and 30 microM, and coumarin 106 was found the most active inhibitor at both concentrations. The follow-up analysis using kinetic studies demonstrated that coumarin 106 displays mixed-type AChE inhibition with a pIC(50)=4.97+/-0.09 and K(i)=2.36+/-0.17 microM. The ability of this molecule to interact with AChE was further confirmed through computational studies, in which a primary binding was proved to occur at the active gorge site, while a secondary binding was demonstrated at the peripheral anionic site. Also, coumarin 106 was shown to inhibit butyrylcholinesterase (BChE) with slightly lower potency (pIC(50)=4.56+/-0.06), and found to be non-toxic in Caco-2 cells. The combination of these findings makes coumarin 106 an attractive molecule for further investigation. This is the first report where AChE inhibitory activity has been associated with coumarin 106, and proof has been given of its convenience as a lead molecule.