Synthesis of 2,2-dimethyl-chroman-based stereochemically flexible and constrained anti-breast cancer agents.

Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC50 value 8.5-25.0 µM. Amongst all, four potential molecules viz 19b, 19e, 22a, and 22c, were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -ß.

Twistronics in two-dimensional transition metal dichalcogenide (TMD)-based van der Waals interface.

Transition metal dichalcogenides (TMD) based heterostructures have gained significant attention lately because of their distinct physical properties and potential uses in electronics and optoelectronics. In the present work, the effects of twist on the structural, electronic, and optical properties (such as the static dielectric constant, refractive index, extinction coefficient, and absorption coefficient) of vertically stacked TMD heterostructures, namely MoSe2/WSe2, WS2/WSe2, MoSe2/WS2 and MoS2/WSe2, have been systematically studied and a thorough comparison is done among these heterostructures. In addition, the absence of negative frequency in the phonon dispersion curve and a low formation energy confirm the structural and thermodynamical stability of all the proposed TMD heterostructures. The calculations are performed using first-principles-based density functional theory (DFT) method. Beautiful Moiré patterns are formed due to the relative rotation of the layers as a consequence of the superposition of the periodic structures of the TMDs on each other. Twist engineering allows the modulation of bandgaps and a phase change from direct to indirect band gap semiconductors as well. The high optical absorption in the visible range of spectrum makes these twisted heterostructures very promising candidates in photovoltaic applications.

Clinical value of placental examination for paediatricians.

The placenta contains valuable clinical information that is linked to fetal development, neonatal morbidity and mortality, and future health outcomes. Both gross inspection and histopathological examination of the placenta may identify intrinsic or secondary placental lesions, which can contribute directly to adverse neonatal outcomes or indicate the presence of an unfavourable intrauterine environment. Placental examination therefore forms an essential component of the care of high-risk neonates and at perinatal post-mortem examination. In this article, we describe the clinical value of placental examination for paediatricians and perinatal clinicians. We discuss common pathological findings on general inspection of the placenta with photographic examples and provide an overview of the placental pathological examination, including how to interpret key findings. We also address the medico-legal and financial implications of placental examinations and describe current and future clinical considerations for clinicians in regard to placental examination.

Side-Chain Modification in Conjugated Polymer Frameworks for the Electrocatalytic Oxygen Evolution Reaction.

Conjugated polymer frameworks (CPFs) have recently sparked tremendous research interest due to their broad potentials in various frontline application areas such as photocatalysis, sensing, gas storage, energy storage, etc. These framework materials, without sidechains or functional groups on their backbone, are generally insoluble in common organic solvents and less solution processable for further device applications. There are few reports on metal-free electrocatalysis, especially oxygen evolution reaction (OER) using CPF. Herein, we have developed two triazine-based donor-acceptor conjugated polymer frameworks by coupling a 3-substituted thiophene (donor) unit with a triazine ring (acceptor) through a phenyl ring spacer. Two different sidechains, alkyl and oligoethylene glycol, were rationally introduced into the 3-position of thiophene in the polymer framework to investigate the effect of side-chain functionality on the electrocatalytic property. Both the CPFs demonstrated superior electrocatalytic OER activity and long-term durability. The electrocatalytic performance of CPF2, which achieved a current density of 10 mA/cm2 at an overpotential (η) of 328 mV, is much superior to CPF1, which reached the same current density at an overpotential of 488 mV. The porous and interconnected nanostructure of the conjugated organic building blocks, which allowed for fast charge and mass transport processes, could be attributed to the higher electrocatalytic activity of both CPFs. However, the superior activity of CPF2 compared to CPF1 may be due to the presence of a more polar oxygen-containing ethylene glycol side chain, which enhances the surface hydrophilicity, promotes better ion/charge and mass transfer, and increases the accessibility of the active sites toward adsorption through lower π-π stacking compared to hexyl side chain present in CPF1. The DFT study also supports the plausible better performance toward OER for CPF2. This study confirms the promising potentiality of metal-free CPF electrocatalysts for OER and further sidechain modification to improve their electrocatalytic property.

Macrothrombocytopenia: Role of Automated Platelet Data in Diagnosis.

Purpose: Inherited macrothrombocytopenia is an underdiagnosed condition and may result in misdiagnosis and inappropriate management. This research was done to study this condition in a hospital setting. Materials and Methods: This study was conducted over 6 months in a teaching hospital. Patients whose complete blood count (CBC) samples were sent to the hematology laboratory were included. Patients were suspected to have inherited macrothrombocytopenia according to pre-defined criteria. Demographic information, automated CBC and peripheral smear examination was carried out. Seventy five healthy individuals and 50 patients with secondary thrombocytopenia were also analyzed. Results: Likely inherited macrothrombocytopenia was identified in 75 patients. Automated platelet count in these patients ranged from 26 × 10^9/L to 106 × 10^9/L while MPV ranged from 11.0 to 13.6 fL. There was significant difference (p < .001) in mean platelet volume (MPV) and platelet large cell ratio (P-LCR) amongst patients with likely inherited macrothrombocytopenia, those with secondary thrombocytopenia and the control group. Mean platelet diameter was significantly higher (3.5 ± 1.1µm) in patients with likely inherited macrothromboctopenia compared to those with secondary thrombocytopenia (2.4 ± 0.7µm) and control group (1.9 ± 0.7µm). All patients with suspected inherited macrothrombocytopenia showed abnormal platelet histograms with descending limb in the high volume and red cell zone. Four distinct histogram patterns were identified. Conclusion: Inherited macrothrombocytopenia is an underdiagnosed condition. The patient's history, clinical examination, judicious use of automated CBC data including platelet histograms and careful review of the peripheral blood smear are useful tools to suspect this condition. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01590-6.

Synthesis of amide derivatives of 3-aryl-3H-benzopyrans as osteogenic agent concomitant with anticancer activity.

The present study reports a series of 3-aryl-3H-benzopyran-based amide derivatives as osteogenic agents concomitant with anticancer activity. Six target compounds viz 22e, 22f, 23i, and 24b-d showed good osteogenic activity at 1 pM and 100 pM concentrations. One of the potential molecules, 24b, effectively induced ALP activity and mRNA expression of osteogenic marker genes at 1 pM and bone mineralization at 100 pM concentrations. These molecules also presented significant growth inhibition of osteosarcoma (MG63) and estrogen-dependent and -independent (MCF-7 and MDA-MB-231) breast cancer cells. The most active compound, 24b, inhibited the growth of all the cancer cells within the IC50 10.45-12.66 µM. The mechanistic studies about 24b showed that 24b induced apoptosis via activation of the Caspase-3 enzyme and inhibited cancer cell migration. In silico molecular docking performed for 24b revealed its interaction with estrogen receptor-ß (ER-ß) preferentially.

Suspected twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy: a case report.

BACKGROUND: Twin anemia polycythemia sequence is a rare complication in monochorionic twin pregnancy. CASE PRESENTATION: We describe a case of dichorionic twin pregnancy presenting with suspected twin anemia polycythemia sequence. A 31-year-old White female, on her third pregnancy, had a routine ultrasound scan at 12 weeks gestation, which demonstrated a dichorionic twin pregnancy with one placenta located in the anterior wall and the other in the posterior wall of the uterus. At 21 weeks, a scan demonstrated a 24% growth discordance between the two fetuses with normal Doppler studies and amniotic fluid. At 27 weeks, one twin showed signs of anemia and the other polycythemia; the fetal middle cerebral artery peak systolic velocity was high in the anemic fetus and low in the polycythemic twin (1.8 and 0.5 multiples of the median). An intrauterine blood transfusion was carried out and this increased the fetal hemoglobin concentration in the anemic twin from 3.5 to 12.5 g/dL. At 29 weeks, delivery by cesarean section was carried out because of evidence from middle cerebral artery peak systolic velocity of recurrence of anemia in one twin and worsening polycythemia in the co-twin; at birth the hemoglobin concentrations were 5.6 and 24.9 g/dL, respectively. Histopathological examination confirmed dichorionicity with no communicating vessels between the two placentas. CONCLUSIONS: This is the first case of twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy where intrauterine blood transfusion was used to prolong the pregnancy by almost 2 weeks in a "twin anemia polycythemia sequence-like" setting.

Psychological implications of Covid-19 in healthcare workers.

BACKGROUND: The Covid-19 outbreak has led to an unprecedented burden on the healthcare infrastructure. High morbidity and mortality rates have resulted in a state of stress and distress among the general population which has also impacted health professionals. AIMS: This study was conducted to identify mental health disturbances among health professionals during the Covid-19 pandemic. MATERIALS AND METHODS: It was a cross-sectional study, conducted in a Medical College in Himachal Pradesh, India. A self-administered anonymized questionnaire was administered to the healthcare workers. Mental health status was assessed using Patient Health Questionnaire Anxiety-Depression Scale (PHQ-ADS). In addition, a 15-item questionnaire was prepared to identify the probable causes of stress in HCWs during the Covid-19 Pandemic. A statistical analysis used t-test was used to find the significance of the correlation between the PHQ-ADS score and the agreement score of different factors. RESULTS: The response rate for the questionnaire was 27%. Anxiety and depression were seen in 29% of participants, ranging from mild (18.3%), moderate (4.7%), and severe (5.9%). Among females 43.7% of the participants and among males, 13.1% had anxiety and depression. High PHQ-ADS scores were seen in nursing staff (70%) and postgraduate students (30%), who were in the third decade of life. Most (81.7%) of the HCWs were concerned about transmitting the disease to their near ones. Fear of coming to the hospital and dealing with patients. CONCLUSION: Even sub-threshold syndromes among HCWs need to be identified before they evolve into overt diseases. The psychological needs of healthcare workers should be prioritized as they are key players in the fight against Covid-19.

A Diagnostic Dilemma in Fine-Needle Aspiration Cytology: Spindle Cell/Pleomorphic Lipoma.

Pleomorphic lipoma is an uncommon, pseudosarcomatous lesion. It is characterized by the pleomorphic appearance on cytology and histology, follows a benign course, with a low rate of recurrence after complete excision, and has no risk of metastasis. Here, we describe a case of pleomorphic lipoma/spindle cell lipoma in a 41-year-old man who presented with a slow-growing mass on the inner aspect of the left thigh. On fine-needle aspiration cytology, it was reported as a cellular nerve sheath tumour followed by a wide excision sample sent for histopathological examination, which revealed spindle cells exhibiting pleomorphism with mature adipocytic cells and multinucleated floret cells in a myxoid background. It was reported as pleomorphic lipoma on histological examination.