Revolutionizing Cancer Treatment: Harnessing the Power of Mesenchymal Stem Cells for Precise Targeted Therapy in the Tumor Microenvironment.

In recent years, mesenchymal stem cells (MSCs) have emerged as promising anti-- cancer mediators with the potential to treat several cancers. MSCs have been modified to produce anti-proliferative, pro-apoptotic, and anti-angiogenic molecules that could be effective against a variety of malignancies. Additionally, customizing MSCs with cytokines that stimulate pro-tumorigenic immunity or using them as vehicles for traditional chemical molecules with anti-cancer characteristics. Even though the specific function of MSCs in tumors is still challenged, promising outcomes from preclinical investigations of MSC-based gene therapy for a variety of cancers inspire the beginning of clinical trials. In addition, the tumor microenvironment (TME) could have a substantial influence on normal tissue stem cells, which can affect the treatment outcomes. To overcome the complications of TME in cancer development, MSCs could provide some signs of hope for converting TME into unequivocal therapeutic tools. Hence, this review focuses on engineered MSCs (En-MSCs) as a promising approach to overcoming the complications of TME.

Palladium-Catalyzed Direct C-H Glycosylation of Free (N-H) Indole and Tryptophan by Norbornene-Mediated Regioselective C-H Activation.

We describe the palladium-catalyzed direct C-H glycosylation of free N-H indole or tryptophan for the stereoselective synthesis of 2-glycosylindoles and tryptophan-C-glycosides. This reaction relies on the ortho-directing transient mediator norbornene, which underwent regioselective C-H functionalization at the indole or tryptophan ring, providing high chemoselectivity. This method offers a more straightforward, step-economical, and cost-effective route to construct C-glycosides. The gram-scale amenable building blocks can be further functionalized at C3 and N-H, displaying the robustness of present method.

Inadvertent strangulation of inflation line of the pilot balloon during submental endotracheal intubation: a rare complication.

Submental intubation is the preferred type of intubation in patients with complex maxillofacial fractures where oral or nasal intubation cannot be performed. It is also less invasive than tracheostomy in securing the airways. We report a case where an inadvertent strangulation of inflation line of the pilot balloon resulted in inadequate ventilation during submental intubation.

Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial)

ObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial. SettingThirty-nine public and private hospitals across India. ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 [≤] 93% on room air). InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment. ResultsBetween 22nd April to 14th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19. Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.

SARS-CoV2 genome analysis of Indian isolates and molecular modelling of D614G mutated spike protein with TMPRSS2 depicted its enhanced interaction and virus infectivity

COVID-19 that emerged as a global pandemic is caused by SARS-CoV-2 virus. The virus genome analysis during disease spread reveals about its evolution and transmission. We did whole genome sequencing of 225 clinical strains from the state of Odisha in eastern India using ARTIC protocol-based amplicon sequencing. Phylogenetic analysis identified the presence of all five reported clades 19A, 19B, 20A, 20B and 20C in the population. The analyses revealed two major routes for the introduction of the disease in India i.e. Europe and South-east Asia followed by local transmission. Interestingly, 19B clade was found to be much more prevalent in our sequenced genomes (17%) as compared to other genomes reported so far from India. The haplogroup analysis for clades showed evolution of 19A and 19B in parallel whereas the 20B and 20C appeared to evolve from 20A. Majority of the 19A and 19B clades were present in cases that migrated from Gujarat state in India suggesting it to be one of the major initial points of disease transmission in India during month of March and April. We found that with the time 20A and 20B clades evolved drastically that originated from central Europe. At the same time, it has been observed that 20A and 20B clades depicted selection of four common mutations i.e. 241 C>T (5UTR), P323L in RdRP, F942F in NSP3 and D614G in the spike protein. We found an increase in the concordance of G614 mutation evolution with the viral load in clinical samples as evident from decreased Ct value of spike and Orf1ab gene in qPCR. Molecular modelling and docking analysis identified that D614G mutation enhanced interaction of spike with TMPRSS2 protease, which could impact the shedding of S1 domain and infectivity of the virus in host cells.

How did SARS-CoV-19 spread in India from Italy, Iran and China? Genetic surveillance of early cases and virus demography

SARS-CoV-19 after emerging from Wuhan, drastically devastated all sectors of human life by crushing down the global economy and increased psychological burden on public, government, and healthcare professionals. We manifested by analyzing 35 early coronavirus cases of India, that virus introduction in India, occurred from Italy, Iran and China and population demography apparently revealed a rapid population expansion after the outbreak with a present steady growth. We depicted nucleotide substitutions in structural genes, drove for the adaptive selection and plead for sequencing more genomes to facilitate identification of new emerged mutants, genetic evolution and disease transmission caused by coronavirus.

Further delineation of CDC45-related Meier-Gorlin syndrome with craniosynostosis and review of literature.

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynostosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders.

To compare intralesional and oral propranolol for treating periorbital and eyelid capillary hemangiomas.

Purpose: A pilot randomized control trial to compare the efficacy and side effects of intralesional and oral propranolol in periorbital and eyelid capillary hemangiomas. Methods: Twenty patients were prospectively randomized to two groups of ten each. Group 1 was initiated on oral propranolol 1 mg/kg/day titrated to final dose of 3 mg/kg/day over 1 week which was continued for 6 months and then tapered over 1 week; Group 2 received 3 doses of direct intralesional propranolol hydrochloride 1 mg/ml; 0.2 ml/cm 4-6 weeks apart. Hemangioma area and corneal astigmatism were measured. Results: Within each group at 6 months there was a significant reduction in area (group 1: 83.48 ± 11.67%,P= 0.0019; group 2: 67.78 ± 21.71%,P= 0.0019) and improvement in astigmatism (pre, post: group 1: 2.98D @ 179.8°, 1.13D @ 179.8°,P= 0.0045; group 2: 1.62D @ 90.16°, 0.75D @ 179.9°,P= 0.0001). There was no difference in area reduction (P = 0.056), change in appearance (P = 0.085), ptosis (P = 0.23) and side effects (lethargy, poor feeding;P= 0.171) between the two groups. Conclusion: Efficacy and side effects with intralesional propranolol are comparable to oral propranolol for periorbital and eyelid lesions.

A novel Ser40Trp variant in IFITM5 in a family with osteogenesis imperfecta and review of the literature.

Osteogenesis imperfecta, is a genetically and clinically heterogeneous connective tissue disorder that disrupts bone architecture, making it fragile and more prone to fractures. While more than 85% of cases are due to variants in COL1A1 and COL1A2, variants in noncollagen genes have been identified in the remaining cases. The recurring heterozygous variant in IFITM5 (c.-14C>T) leads to osteogenesis imperfecta type V, a second missense variant in IFITM5 (c.119C>T, p.Ser40Leu) leads to phenotype resembling osteogenesis imperfecta type VI. In this report, we describe the first patient with Ser40Trp variant in IFITM5, who presented with multiple fractures in the prenatal period. She remained fracture free after birth (except for trauma-related fractures during puberty) with normal bone mineral densitometry. Her mother, who did not have a history of fracture, was noted to have somatogonadal mosaicism for this variant and became pregnant with a second child with multiple prenatal fractures, found to have the same variant. To our knowledge, this is the first case of somatogonadal mosaicism in IFITM5. In addition, we have summarized the literature on patients presenting with variant in codon 40 (serine) of IFTIM5 protein.

Ambiguous pediatric endotracheal tube intubation depth markings: a need for standardization / 대한마취과학회지

No abstract available.

A Prospective Study of Anterior Segment Ocular Parameters in Anisometropia

PURPOSE: The aim of this study was to investigate the differences in anterior segment ocular parameters in anisometropia >1 D. METHODS: This study included 202 eyes of 101 subjects ranging from 10 to 40 years of age with anisometropia of 1 D or more. The subjects were divided into groups according to anisomyopia, anisoastigmatism, and anisohypermetropia. After providing informed consent, each patient underwent a detailed ophthalmological examination including cycloplegic refraction, best-corrected visual acuity, cover test, axial length (AL) measurement using A-scan ultrasound biometer, keratometry, anterior chamber depth, and central corneal thickness measurement. For each participant, the eye with greater refractive error was compared to the fellow eye via paired t-tests. Correlations between parameters were studied using the Pearson correlation coefficient. RESULTS: The average age of subjects was 21.7 ± 9.3 years. Of 101 subjects, 31 had anisomyopia; 42 had anisohypermetropia; and 28 had anisoastigmatism. A predisposition toward greater myopia in right eyes was noted in anisomyopia (24 of 31 subjects, 77%). The inter-ocular acuity difference was significant in all three groups (p < 0.01). As the degree of anisometropia increased, there was significant positive correlation in the difference in AL in myopes (r = 0.863, p < 0.01) and hypermetropes (r = 0.669, p < 0.01) and the difference in corneal curvature in anisoastigmatism (r = 0.564, p = 0.002) and hypermetropes (r = 0.376, p = 0.014). A significant positive correlation was also present between the anterior chamber depth difference and refractive difference in hypermetropes (r = 0.359, p = 0.020). CONCLUSIONS: This study showed that anisomyopia is correlated only with anterior chamber differences. Anisohypermetropia is correlated with AL differences as well as corneal curvature difference and anterior chamber depth difference. The amount of anisoastigmatism correlates only with corneal curvature difference.

Central venous catheter malposition due to dialysis catheter: a case report / 대한마취과학회지

A 56-year-old man on maintenance hemodialysis was admitted to the intensive care unit with septic shock and coagulopathy. As there was a dialysis catheter in the right internal jugular vein, the left internal jugular vein was cannulated with a central venous catheter to initiate vasopressor therapy. A chest X-ray showed formation of a catheter loop inside the left brachiocephalic vein, probably due to hindrance by the dialysis catheter. This report describes the hurdles encountered, repeated cannulation attempts, and serial chest X-ray findings required to obtain acceptable placement of the catheter tip.