Nasal Pyriform Aperture Stenosis in a Newborn: When to Operate.

Congenital nasal pyriform aperture stenosis (CNPAS) is a very rare cause of neonatal respiratory distress and is often missed because of its rarity. It arises from the overgrowth of the nasal process of the maxilla. Maxillofacial CT scan findings of pyriform aperture width <11 mm in a full-term baby, median central incisor, triangular-shaped palate, and median palatal ridge confirm the diagnosis. We describe here a case of CNPAS admitted with respiratory distress that increased further on feeding. An infant feeding tube of size 6 was not negotiable through the nostrils. Resistance was appreciated at the inlet of the nostril. Maxillofacial CT showed pyriform aperture stenosis of 3.4 mm, suggesting CNPAS. The child could not be weaned off a high-flow nasal cannula despite conservative management with decongestants, steroids spray, dilatation, and stenting for 20 days. Subsequently, surgical widening of the nasal aperture by a sublabial approach was done. The child was discharged on the 10th postoperative day on full oral feeds. It is important to suspect CNPAS in neonates with respiratory distress where other common causes have been ruled out, as it can be treated by surgery in cases refractory to conservative management.

Financial toxicity in gynecologic oncology: a multi-practice survey.

BACKGROUND: Financial toxicity is associated with worse cancer outcomes, including lower survival. OBJECTIVE: To characterize the prevalence of, and patient risk factors for, financial toxicity among gynecologic oncology patients in a multi-site health system. METHODS: We identified patients seen in University of Pennsylvania gynecologic oncology practices between January 2020 and February 2022 with a patient portal account. We sent a survey to all alive patients twice between March and April 2022, including the 11-item Comprehensive Score for Financial Toxicity (COST) tool. We compared differences between patients reporting high (COST score <26) and low financial toxicity (COST score ≥26) in Χ2 and regression analyses. RESULTS: Of 8239 patients, 6925 had a portal account, and 498 completed the survey for 7.2% response rate. 44% had a COST score <26, indicating financial toxicity. Patients with high financial toxicity were more likely to be younger (mean age 54 vs 60), have cervical cancer (10% vs 4%; p=0.008), be privately insured (71% vs 57%; p=0.003) or have Medicaid (7% vs 3%; p=0.03), or be unemployed (18% vs 3%; p=<0.001), and less likely to be white (79% vs 90%, p=0.003) than those with low financial toxicity. Patients with Medicare were less likely to experience financial toxicity than privately insured patients (RR=0.59, 95% CI 0.37 to 0.95). CONCLUSION: In this study of patients with gynecologic cancer or pre-cancer, 44% had financial toxicity. Financial toxicity was higher in patients who were younger, did not identify as White, and had private insurance. Targeted measures to address financial toxicity are needed to minimize disparities in patient burden of cancer treatment.

Understanding Moral Injury in Frontline Health Care Professionals 2 Years After the Onset of COVID-19.

ABSTRACT: Throughout the COVID-19 pandemic, health care professionals have worked in morally challenging situations. The aim of this research was to investigate the predictors of moral injury in United Kingdom frontline health care professionals working in a variety of roles 2 years after the onset of the pandemic. A cross-sectional survey was conducted January 25-February 28, 2022. A total of 235 participants answered sociodemographic, employment, health, COVID-19-related questions, and the 10-item Moral Injury Symptom Scale-Healthcare Professional version. Nearly three quarters had experienced moral injury. Twelve significant predictors of moral injury were entered into a backward elimination binominal logistic regression. The final model included five independent predictors that explained 25.4% variance in moral injury (χ 2 [5, N = 235] = 45.7, p < 0.001). Odds of moral injury were significantly raised in young health care professionals (<31 years), smokers, and those reporting low workplace confidence, not feeling appreciated, and feeling burned out. The findings support interventions to relieve moral injury in frontline health care professionals.

Antioxidant, Antidiabetic and Lipid Profiling of Spermadicyton Suaveolens in Streptozotocin (STZ) Induced Diabetic Rats

ABSTRACT Diabetes is a life-threatening disease, and currently available synthetic medicines for treating diabetes are associated with various side effects. Therefore, there is an unmet need to develop herbal remedies against diabetes as an alternative to synthetic medicines. Although local healers use the roots of Spermadicyton suaveolens (SS) to manage diabetes, there is negligible research to validate its antidiabetic properties. The present investigation aims to the assess the antioxidant, antidiabetic, and antihyperlipidemic potential of the ethanolic extract of S. Suaveolen's roots (EESS) on streptozotocin (STZ) induced diabetic rats. The extract was screened for in vitro antioxidant and antidiabetic activity. The in vivo antidiabetic potential of EESS (at 200 and 400 mg/kg) was studied on STZ-induced diabetic rats for 20 days. The EESS displayed significant (p<0.05) antidiabetic and antioxidant properties. The administration of 200 mg/kg and 400 mg/kg EESS in STZ-induced diabetic rats significantly reduced hyperglycemia, and restored antioxidant enzymes and lipid profile-a high density lipoprotein (HDL) increased by the administration of a single dose of streptozotocin. Thus, EESS could be a promising herbal medicine in the treatment of diabetes and hyperlipidemia

Optimization of Methods for the Production and Refolding of Biologically Active Disulfide Bond-Rich Antibody Fragments in Microbial Hosts.

Antibodies have been used for basic research, clinical diagnostics, and therapeutic applications. Escherichia coli is one of the organisms of choice for the production of recombinant antibodies. Variable antibody genes have canonical and non-canonical disulfide bonds that are formed by the oxidation of a pair of cysteines. However, the high-level expression of an antibody is an inherent problem to the process of disulfide bond formation, ultimately leading to mispairing of cysteines which can cause misfolding and aggregation as inclusion bodies (IBs). This study demonstrated that fragment antibodies are either secreted to the periplasm as soluble proteins or expressed in the cytoplasm as insoluble inclusion bodies when expressed using engineered bacterial host strains with optimal culture conditions. It was observed that moderate-solubilization and an in vitro matrix that associated refolding strategies with redox pairing more correctly folded, structured, and yielded functionally active antibody fragments than the one achieved by a direct dilution method in the absence of a redox pair. However, natural antibodies have canonical and non-canonical disulfide bonds that need a more elaborate refolding process in the presence of optimal concentrations of chaotropic denaturants and redox agents to obtain correctly folded disulfide bonds and high yield antibodies that retain biological activity.

Antimicrobial, anti-inflammatory and wound healing activity of polyherbal formulation.

According to Ayurveda, individual herbs are insufficient to achieve a desired therapeutic effect. When it is optimized as multiple herbs composition in a particular ratio it will give a therapeutic effect in a better way with reduced toxicity. In order to develop such an intervention, the present study was intended to develop a polyherbal drug from methanolic extracts of Plumbago zeylanica Linn, Datura stramonium Linn and Argemone mexicana Linn. The study also aimed to evaluate the impact of polyherbalism on antimicrobial and antioxidant effect, thereafter the ratio of individual plant extracts was optimized accordingly to treat the wound. The poyherbal drug was put on preclinical trial to access the anti-inflammatory and wound healing activity as 2% and 5% polyherbal carbopol-940 gels. The antimicrobial activity was assessed by agar well diffusion and broth dilution method while wound healing activity was evaluated by excision and incision wound models. Topical anti-inflammatory activity was assessed by carrageenan induced paw oedema. The findings of the study revealed the synergistic antimicrobial potential of Polyherbal drug against gram-positive and negative strains. Polyherbal carbopol- 940 gels (2% and 5%w/w) promoted the wound healing and anti-inflammatory effect. The high rate of wound contraction (<0.0001), early epithelialization period (<0.0001) and increased wound breaking strength (<0.0001) were observed in 2% and 5% polyherbal gel treated group when compared to the normal control and negative control group. The antimicrobial and anti-inflammatory effect of Polyherbal drug provoked and promoted the wound healing process through accelerated remodelling of damaged tissue.

Superabsorbent nanocomposite from sugarcane bagasse, chitin and clay: Synthesis, characterization and swelling behaviour.

A nanocomposite comprising crosslinked hybrid polymer network was prepared using chitin and sugarcane bagasse in presence of montmorillonite clay. Chitin and sugarcane bagasse were micro-fibrillated by ultrasonication of their suspension in an ionic liquid 2-hydroxy ethylammonium formate. Optimum reaction conditions were established by variation of amounts of initiator, monomer and crosslinker, and microwave irradiation to obtain nanocomposite with swelling degree above 1000% in 24 h. Slow and steady swelling was observed and the sample swelled to about 15,000% to form a hydrogel in 15 days. The nanocomposite was characterized by swelling degree, infrared spectroscopy, X-ray diffraction and scanning electron microscopy. Swelling and reswelling in water was studied for four cycles, erosion was highest after first cycle but became negligible for consecutive cycles. The swelling degree increased up to three cycles then became constant. Nanocomposite shows sufficient antimicrobial activity against S. aureus and E. coli. It is biodegradable in moist garden soil in three months.

Poly(vinylidene fluoride)-based flexible and lightweight materials for attenuating microwave radiations.

Two unique materials were developed, like graphene oxide (GO) sheets covalently grafted on to barium titanate (BT) nanoparticles and cobalt nanowires (Co-NWs), to attenuate the electromagnetic (EM) radiations in poly(vinylidene fluoride) (PVDF)-based composites. The rationale behind using either a ferroelectric or a ferromagnetic material in combination with intrinsically conducting nanoparticles (multiwall carbon nanotubes, CNTs), is to induce both electrical and magnetic dipoles in the system. Two key properties, namely, enhanced dielectric constant and magnetic permeability, were determined. PVDF/BT-GO composites exhibited higher dielectric constant compared to PVDF/BT and PVDF/GO composites. Co-NWs, which were synthesized by electrodeposition, exhibited saturation magnetization (Ms) of 40 emu/g and coercivity (Hc) of 300 G. Three phase hybrid composites were prepared by mixing CNTs with either BT-GO or Co-NWs in PVDF by solution blending. These nanoparticles showed high electrical conductivity and significant attenuation of EM radiations both in the X-band and in the Ku-band frequency. In addition, BT-GO/CNT and Co-NWs/CNT particles also enhanced the thermal conductivity of PVDF by ca. 8.7- and 9.3-fold in striking contrast to neat PVDF. This study open new avenues to design flexible and lightweight electromagnetic interference shielding materials by careful selection of functional nanoparticles.

Anomalous structural relaxations in PVDF rich blends with PMMA in the presence of surface functionalized CNTs.

The structural relaxations in PVDF rich blends with PMMA can be quite interesting in understanding the origin of the different molecular relaxations associated with the crystalline and amorphous phases, crystal-amorphous interphase and the segmental motions. In light of our recent findings, we understood that the origin of these molecular relaxations were strongly contingent on the concentration of PMMA in the blend, crystalline morphology and the surface functional moieties on multiwall carbon nanotubes (CNTs). In addition, for the blends with concentration of PMMA ≥ 25 wt%, the structural relaxations often merge and are dielectrically indistinguishable. In this study, we attempted to determine the critical width in composition where the structural relaxations can be distinctly realized both in the control as well as blends with amine functionalized CNTs (NH2-CNTs). Intriguingly, we observed that in a narrow zone in composition (with PMMA concentration ≥ 10 wt% and ≤25 wt%), the molecular relaxations can be dielectrically distinguished and they often merge for all other compositions. Furthermore, we attempted to understand how this critical width in composition is related to the crystalline morphology using small angle X-ray scattering and polarizing optical microscopy and the crystal structure using FTIR and Raman spectroscopy. We now understand that although the formation of ß crystals in the blends has no direct correlation with the observed molecular relaxations, the amorphous miscibility and the interphase regions seem to be dictating the origin of different molecular relaxations in the blends. The latter was observed to be strongly contingent on the concentration of PMMA in the blends.

Shear induced crystallization in different polymorphic forms of PVDF induced by surface functionalized MWNTs in PVDF/PMMA blends.

Shear induced crystallization in PVDF/PMMA blends, especially at higher fractions of PMMA, can be quite interesting in understanding the structure-property correlation and processing of these blends. In a recent submission (Phys. Chem. Chem. Phys., 2014, 16, 2693-2704), we clearly demonstrated, using dielectric spectroscopy, that the origin of segmental relaxations concerning the crystalline segments of PVDF in PVDF/PMMA blends in the presence of MWNTs (multiwalled nanotubes) was strongly contingent on the size of the crystallite. We now understand that the fraction of PMMA in the blends governs the origin of polymorphism in PVDF. This motivated us to systematically study the effect of shear on the crystallization behavior of PVDF especially in blends with different polymorphic forms of PVDF. Two model blends were selected; one with a mixture of α and ß crystals and the other predominantly rich in α crystals. Initially, physical ageing, at different oscillation frequencies (1 rad s(-1) and 0.1 rad s(-1)), was monitored by melt rheology and subsequently, the effect of steady shear was probed in situ without changing the history of the samples. Intriguingly, the rate of crystallization was observed to be significantly higher for higher oscillation frequencies, which essentially suggest that shear has induced crystallization in the blends. More interestingly, the effect of steady shear was more pronounced in the blends rich in α crystals (bigger crystallites as observed from SAXS) and at lower oscillation frequencies.

Process induced electroactive ß-polymorph in PVDF: effect on dielectric and ferroelectric properties.

The effects of various processing conditions, like annealing, poling, mechanical rolling and their combinations, on the dielectric and ferroelectric properties of PVDF [poly(vinylidene fluoride)] were systematically studied in this work. Further, the effect of processing sequence on the structure and properties was investigated. While all the processing conditions adopted here resulted in phase transformation of the α- to electroactive ß-polymorph in PVDF, the fraction of ß-phase developed was observed to be strongly contingent on the adopted process. The transformation of α to electroactive ß-polymorph was determined by X-ray diffraction and FTIR. The neat PVDF showed only α-phase, whereas mechanically rolled samples exhibited the highest ca. 85% ß-phase in PVDF. Both the permittivity and the loss tangent decreased in the samples which had undergone different processing conditions. The polarization-electric field (P-E) loops for all the samples were evaluated. Interestingly, the energy density, estimated from the electrical displacement-electric field (D-E) loops, was observed to be highest for the poled samples which were initially rolled. The results indicate that various processing conditions can influence the dielectric and the ferroelectric properties differently.

Carotid intima-media thickness: Current evidence, practices, and Indian experience.

As the developed and developing nations cope up with increasing predisposition to cardiovascular diseases (CVD) by adopting lifestyle changes the burden of coronary artery disease continues to rise globally. The presence of modifiable risk factors, which account for more than 90% of the cardiovascular (CV) risk, cannot always be interpreted as the presence of atherosclerotic heart disease and absence of modifiable risk factors do not guarantee absence of atherosclerotic changes in the arterial tree. Increasing awareness about primordial prevention and primary prevention of CVD is of vital importance in such scenarios. Ultrasonographic measurement of intima media thickness has been reported as a procedure to detect the early stages of atherosclerosis. Carotid intima media thickness (CIMT) testing is a safe, noninvasive and cost effective method to detect early atherosclerotic vascular diseases. This method of CV risk evaluation drew attention worldwide and of Indian physicians because of its feasibility in Indian population. Hence, detection and management of atherosclerosis in asymptomatic individuals will go a long way in preventing atherosclerotic diseases and prolonging survival and improving quality of life.

Size dependent structural relaxations and dielectric properties induced by surface functionalized MWNTs in poly(vinylidene fluoride)/poly(methyl methacrylate) blends.

Structural dynamics, dielectric permittivity and ferroelectric properties in poly(vinylidene fluoride) (PVDF)/poly(methyl methacrylate) (PMMA) (PVDF/PMMA) blends with respect to crystalline morphology was systematically investigated in presence of amine functionalized MWNTs (NH2-MWNTs) using dielectric spectroscopy. The crystalline morphology and the crystallization driven demixing in the blends was assessed by light microscopy (LM), wide angle X-ray diffraction (WXRD) and, in situ, by shear rheology. The crystal nucleation activity of PVDF was greatly induced by NH2-MWNTs, which also showed two distinct structural relaxations in dielectric loss owing to mobility confinement of PVDF chains and smaller cooperative lengths. The presence of crystal-amorphous interphase was supported by the presence of interfacial polarization at lower frequencies in the dielectric loss spectra. On contrary, the control blends showed a single broad relaxation at higher frequency due to defective crystal nuclei. This was further supported by monitoring the dielectric relaxations during isothermal crystallization of PVDF in the blends. These observations were addressed with respect to the spherulite sizes which were observed to be larger in case of blends with NH2-MWNTs. Higher dielectric permittivity with minimal losses was also observed in blends with NH2-MWNTs as compared to neat PVDF. Polarization obtained using P-E (polarization-electric field) hysteresis loops was higher in case of blends with NH2-MWNTs in contrast to control blends and PVDF. These observations were corroborated with the charge trapped at the crystal-amorphous interphase and larger crystal sizes in the blends with NH2-MWNTs. The microstructure and localization of MWNTs were assessed using SEM.

Segmental relaxations and crystallization-induced phase separation in PVDF/PMMA blends in the presence of surface-functionalized multiwall carbon nanotubes.

Crystallization-induced phase separation and segmental relaxations in poly(vinylidene fluoride)/poly(methyl methacrylate) (PVDF/PMMA) blends was systematically investigated by melt-rheology and broadband dielectric spectroscopy in the presence of multiwall carbon nanotubes (MWNTs). Different functionalized MWNTs (amine, -NH2; acid, -COOH) were incorporated in the blends by melt-mixing above the melting temperature of PVDF, where the blends are miscible, and the crystallization induced phase separation was probed in situ by shear rheology. Interestingly, only -NH2 functionalized MWNTs (a-MWNTs) aided in the formation of ß-phase (trans-trans) crystals in PVDF, whereas both the neat blends and the blends with -COOH functionalized MWNTs (c-MWNTs) showed only α-phase (trans-gauche-trans-gauche') crystals as inferred from wide-angle X-ray diffraction (WXRD) and Fourier transform infrared (FTIR). Furthermore, blends with only a-MWNTs facilitated in heterogeneous nucleation in the blends manifesting in an increase in the calorimetric crystallization temperature and hence, augmented the rheologically determined crystallization induced phase separation temperature. The dielectric relaxations associated with the crystalline phase of PVDF (αc) was completely absent in the blends with a-MWNTs in contrast to neat blends and the blends with c-MWNTs in the dielectric loss spectra. The relaxations in the blends investigated here appeared to follow Havriliak-Negami (HN) empirical equations, and, more interestingly, the dynamic heterogeneity in the system could be mapped by an extra relaxation at higher frequency at the crystallization-induced phase separation temperature. The mean relaxation time (τHN) was evaluated and observed to be delayed in the presence of MWNTs in the blends, more prominently in the case of blends with a-MWNTs. The latter also showed a significant increase in the dielectric relaxation strength (Δε). Electron microscopy and selective etching was used to confirm the localization of MWNTs in the amorphous phases of the interspherulitic regions as observed from scanning electron microscopy (SEM). The evolved crystalline morphology, during crystallization-induced phase separation, was observed to have a strong influence on the charge transport processes in the blends. These observations were further supported by the specific interactions (like dipole induced dipole interaction) between a-MWNTs and PVDF, as inferred from FTIR, and the differences in the crystalline morphology as observed from WXRD and polarized optical microscopy (POM).

Part 1. modular approach to obtaining diverse tetrahydroquinoline-derived polycyclic skeletons for use in high-throughput generation of natural-product-like chemical probes.

A practical synthesis of a tetrahydroaminoquinoline scaffold (12) was developed that used a stereocontrolled aza Michael as the key reaction. Three tetrahydroquinoline alkaloid-like, tricyclic derivatives 16, 18, and 19 with different medium to macrocyclic ring skeletons were obtained, using this scaffold as the starting material, in a modular manner. The macrocyclic compounds with an isolated olefin and an electron-deficient olefin were obtained by ring-closing metathesis approaches. Compounds 16 and 18 are unique and contain bridged 10- and 12-membered functionalized rings. The NMR studies of these compounds revealed interesting information on the conformation of the bicyclic scaffolds that was dependent on the nature and the size of the macrocyclic rings. Finally, this modular methodology, using compound 21 anchored onto the solid support, successfully led to the generation of different macrocyclic derivatives, 23, 25, and 27 in solid-phase synthesis. The solid-phase synthesis approach outlined in this article has the potential to generate tetrahydroquinoline-based tricyclic compounds containing different medium to macrocyclic architectures.

Part 2: building diverse natural-product-like architectures from a tetrahydroaminoquinoline scaffold. Modular solution- and solid-phase approaches for use in high-throughput generation of chemical probes.

The solution- and solid-phase synthesis to obtain several natural-product-like, tetrahydroquinoline-based, polycyclic derivatives were developed. In one approach, two derivatives (38 and 41) having an eight-membered unsaturated lactam were successfully obtained both in solution and on solid support.