Shining light for organophotocatalysed site-selective sulfonylation of anilides.

The site-selective sulfonylation of C(sp2)-H bonds of anilide and quinoline amide derivatives has been developed using organophotocatalysis. This mild and sustainable protocol, which operates at room temperature, precludes the requirement for any metal-based catalyst or photocatalyst and oxidant, which are the challenges associated with existing methodologies. Furthermore, the generation of aryl sulfonyl radicals from commercially available aryl sulfonyl chlorides has been achieved through the use of Rose Bengal as an organophotocatalyst, an approach that was previously unexplored. The detailed mechanistic investigation unveiled the underlying mechanism for site-selective sulfonylation at both the proximal and distal positions, thereby establishing a straightforward approach for building valuable aryl sulfone scaffolds.

Is Orbital Lobe of the Lacrimal Gland Dispensable? Tear Volume, Ocular Surface, and MRI Volumetric Analysis.

PURPOSE: To investigate the effects of lacrimal gland reduction surgeries on the tear volume and ocular surface. METHODS: This is a cohort study of patients post 2 lacrimal gland reduction surgeries: partial orbital lobe dacryoadenectomy for refractory epiphora (4 patients, mean age: 31 ± 13.6 years, 3 males) and complete orbital lobe dacryoadenectomy for lacrimal gland pleomorphic adenoma (15 patients, mean age: 41 ± 12 years, 7 females). Changes in Schirmer I, ocular surface staining, symptomatology, and lacrimal gland volumetrics (MRI) were assessed before and after the surgical procedure. RESULTS: The median Schirmer value reduction following partial orbital lobe dacryoadenectomy was 5 mm at a mean follow-up of 18 ± 4.9 months. None of them developed dry eye disease or positive ocular staining. The gland volume was reduced by 45.9% to 53.5% in 3 patients and 13.3% in 1 patient. The epiphora improved moderately in 93% of patients. Of 15 patients with lacrimal gland pleomorphic adenoma excision, the median reduction in Schirmer I was 4 mm at a mean follow-up of 12.8 months. CONCLUSION: Partial or complete removal of the orbital lobe of the lacrimal gland does not induce dry eye disease in otherwise healthy individuals. However, gland volume does not recover following partial reduction, and it seems unlikely that the lacrimal gland regenerates following partial removal.

An environmentally benign process to synthesize vanillin and other substituted phenyl aldehydes using natural phenylpropenes.

The limited vanillin (3a) production from plant sources requires identifying some renewable and sustainable approaches for its synthesis. This study aimed to develop an efficient, eco-friendly process for synthesizing vanillin (3a) from eugenol (1a) and eugenol-rich essential oils. The chemical methodology for vanillin (3a) synthesis involved base-mediated isomerization of eugenol (1a) to isoeugenol (2a), followed by OsO4/NaIO4 mediated oxidation of isoeugenol to vanillin (3a) using different additives such 1,4-diazabicyclo[2.2.2]octane (DABCO) and substituted pyridines in reusable environment-friendly solvents. Use of 2,6-dimethylpyridine and 2,6-dimethylpyridine N-oxide as additives in the oxidation step offered a significantly higher product yield (vanillin 3a, 70 %). The process synthesized vanillin (3a) irrespective of the cis/ trans stereochemistry of isoeugenol (2a). The peculiarity of the method relates to converting eugenol (1a) to vanillin (3a) without phenolic group protection, which offers step economy. Besides efficient vanillin (3a) synthesis, the process's general implications involve converting other naturally occurring phenylpropenes or phenylpropenes-enriched oils to the corresponding phenyl aldehydes (59-82 % yield).

Long-term outcomes of eyelash-sparing surgical technique for severe segmental cicatricial entropion.

PURPOSE: To assess the long-term outcomes of segmental entropion correction using anterior lamellar recession (ALR) with mucous membrane graft (MMG). METHODS: Prospective interventional study of 16 patients (mean age, 35.3 ± 16.3 years; 10 females) with severe segmental cicatricial entropion, managed using ALR and MMG. Outcome measures include eyelid and eyelash status, changes in the ocular surface, visual acuity, and cosmetic appearance at a minimum nine months of follow-up. RESULTS: Of 16 patients (16 eyelids), 11 had Stevens-Johnson Syndrome (SJS) and five had chemical injury. The most common location of entropion was medial (87.5%) followed by central and lateral. All patients had severe entropion with trichiatic eyelashes. Anatomical success was 87.5% (14/16) at six weeks of follow-up. Residual trichiasis was managed with a repeat ALR with MMG in one and eyelash resection in the other eyelid. The etiology-wise success rates were 90% in SJS and 80% in chemical injury. At the final mean follow-up of 14.8 months, entropion was corrected in 100% of eyelids. None of the patients had cosmetic concerns. Ocular surface symptomatology and visual acuity improved in 87.5% of patients and 40% of eyes, respectively. CONCLUSION: Anterior lamellar recession with lid margin mucous membrane grafting successfully repairs the severe segmental cicatricial entropion without raising any cosmetic concerns.

Clinical utility of plasma cell-free DNA (cfDNA) in diffuse gliomas for the detection of IDH1 R132H mutation.

Liquid biopsy for CNS tumors is in its nascent phase, hindered by the low levels of circulating tumor DNA (ctDNA). Overcoming this challenge requires highly sensitive molecular techniques. DD-PCR emerges as a standout technique due to its ability to identify rare mutations, copy number variations, and circulating nucleic acids, making it one of the best methods for identifying somatic mutations in cell-free DNA (cfDNA). Despite promising results from various studies demonstrating the feasibility of obtaining informative ctDNA profiles from liquid biopsy samples, challenges persist, including the need to standardize sample collection, storage, and processing methods, define clear assay positivity thresholds, and address the overall low assay sensitivity. Our two-phase study began by assessing DD-PCR efficacy in FFPE tissues, revealing robust concordance with immunohistochemistry. In Phase 1 (85 cases), DD-PCR on FFPE tissues demonstrated 100 % sensitivity and specificity for IDH1 R132H mutations. In Phase 2 (100 cases), analysis extended to cfDNA, maintaining high specificity (100 %) with moderate sensitivity (44.2 %). Overall concordance with immunohistochemistry was 61 %, highlighting liquid biopsy's potential in glioma management. The findings emphasized DD-PCR's clinical utility in both tissue and liquid biopsy, underscoring its role in early detection, diagnosis, and therapeutic monitoring of diffuse gliomas.

Identification of key genes and molecular pathways regulating heat stress tolerance in pearl millet to sustain productivity in challenging ecologies.

Pearl millet is a nutri-cereal that is mostly grown in harsh environments, making it an ideal crop to study heat tolerance mechanisms at the molecular level. Despite having a better-inbuilt tolerance to high temperatures than other crops, heat stress negatively affects the crop, posing a threat to productivity gain. Hence, to understand the heat-responsive genes, the leaf and root samples of two contrasting pearl millet inbreds, EGTB 1034 (heat tolerant) and EGTB 1091 (heat sensitive), were subjected to heat-treated conditions and generated genome-wide transcriptomes. We discovered 13,464 differentially expressed genes (DEGs), of which 6932 were down-regulated and 6532 up-regulated in leaf and root tissues. The pairwise analysis of the tissue-based transcriptome data of the two genotypes demonstrated distinctive genotype and tissue-specific expression of genes. The root exhibited a higher number of DEGs compared to the leaf, emphasizing different adaptive strategies of pearl millet. A large number of genes encoding ROS scavenging enzymes, WRKY, NAC, enzymes involved in nutrient uptake, protein kinases, photosynthetic enzymes, and heat shock proteins (HSPs) and several transcription factors (TFs) involved in cross-talking of temperature stress responsive mechanisms were activated in the stress conditions. Ribosomal proteins emerged as pivotal hub genes, highly interactive with key genes expressed and involved in heat stress response. The synthesis of secondary metabolites and metabolic pathways of pearl millet were significantly enriched under heat stress. Comparative synteny analysis of HSPs and TFs in the foxtail millet genome demonstrated greater collinearity with pearl millet compared to proso millet, rice, sorghum, and maize. In this study, 1906 unannotated DEGs were identified, providing insight into novel participants in the molecular response to heat stress. The identified genes hold promise for expediting varietal development for heat tolerance in pearl millet and similar crops, fostering resilience and enhancing grain yield in heat-prone environments.

Punctal cautery in dry eye disease: A systematic review.

PURPOSE: To critically appraise the evidence on the efficacy and recanalization rates of permanent punctal occlusion via thermal or surgical means in managing dry eye disease (DED). METHODS: In PubMed, Scopus, and Cochrane databases, two authors systematically reviewed the literature for prospective studies on punctal cautery or surgical occlusion (excluding punctal plugs) for DED. The studied outcomes were changes in tear volume, tear film stability, punctal recanalization rates, and patient symptomatology. RESULTS: Nine studies (all single-arm) had 150 subjects (96 females). Five studies were on thermal punctal cauterization, and four used surgical occlusion techniques. One hundred eighty puncta were operated for eyes not responding to maximal lubricants or recurrent plug extrusion. DED etiologies were Sjogren's syndrome (78), cicatricial ADDE (27), graft-versus-host disease (12), and non-SS DED (50). Follow-up ranged from 3 to 24 months. At the final follow-up, improvements in Schirmer I and TBUT were 2.5 mm and 0.8s with thermal and 2.1 mm and 0.6s with surgical methods, respectively (P = 0.17 for Schirmer, P = 0.18 for TBUT). Punctal recanalization rates varied between thermal (0-38.7 %) and surgical (5-9%) techniques (p = 0.22). Different cautery devices show different recanalization rates; disposable thermal cautery tips directly inserted into the punctum had lesser recanalization than radiofrequency monopolar cautery. Most patients reported subjective improvement following the procedure, but no quantification measure was given in the studies. None of the published studies had a comparison group for performing a meta-analysis. CONCLUSION: Based on non-comparative studies, thermal or surgical punctal occlusion improves tear volume in DED with similar recanalization rates; however, randomized controlled trials are needed to ascertain the real effects of punctal cautery on DED.

Analysis of sociodemographic profile of glaucoma patients with risk factors, subtypes, and disease severity in a tertiary eye care facility in Northern India.

PURPOSE: To study the different subtypes of glaucoma and to analyze the demographic and clinical profile of glaucoma patients along with associated risk factors in a multi-locational North Indian study. METHODS: Newly diagnosed and known glaucoma patients on treatment were enrolled in the study. Complete history was taken, and clinical evaluation was done by senior glaucoma experts. RESULTS: Five hundred and eighty-six patients (1121 eyes) were included with 383 males (65.4%) and 203 females (34.6%). Of these, 508 (86.7%) had primary glaucoma and 78 (13.3%) had secondary glaucoma. Also, 263 (44.9%) patients had primary open angle glaucoma (POAG) and 172 (29.4%) had primary angle closure glaucoma. Four hundred and fifty-one (77%) were graduates or postgraduates and 293 (50%) were dependents on family income. One hundred and forty-one (24%) had a positive family history. Secondary glaucoma patients had a lower average age (52.6 ± 16.8 years) and higher average intraocular pressure (IOP; 34.23 ± 13 mm) compared to primary glaucoma patients (26.6 ± 9.7 mm) (P < 0.0001). Thirty-three (47.8%) out of 78 secondary glaucoma patients had advanced disease. Seventy-four (12.6%) were first-time diagnosed and 18 had advanced disease. In addition, 161 eyes had one or more glaucoma surgeries done (128 trabeculectomy and 28 phacotrabeculectomy). Ninety-five (16.2%) patients were advised surgery at our centers (46 trab, 26 phacotrab, 15 phaco, five Ahmed glaucoma valve implantation, and three pars plana vitrectomy). Disease progression was noted in 62 patients reporting good compliance to medicines. CONCLUSION: POAG was the most common variant in this study. Secondary glaucoma patients were youngest in age and had the highest IOP. Trabeculectomy was the most performed surgery. A good literacy rate did not prevent late presentations.

D-galactonate metabolism in enteric bacteria: a molecular and physiological perspective.

D-galactonate, a widely prevalent sugar acid, was first reported as a nutrient source for enteric bacteria in the 1970s. Since then, decades of research enabled a description of the modified Entner-Doudoroff pathway involved in its degradation and reported the structural and biochemical features of its metabolic enzymes, primarily in Escherichia coli K-12. However, only in the last few years, the D-galactonate transporter has been characterized, and the regulation of the dgo operon, encoding the structural genes for the transporter and enzymes of D-galactonate metabolism, has been detailed. Notably, in recent years, multiple evolutionary studies have identified the dgo operon as a dominant target for adaptation of E. coli in the mammalian gut. Despite considerable research on dgo operon, numerous fundamental questions remain to be addressed. The emerging relevance of the dgo operon in host-bacterial interactions further necessitates the study of D-galactonate metabolism in other enterobacterial strains.

Complex interplay between RAS GTPases and RASSF effectors regulates subcellular localization of YAP.

RAS GTPases bind effectors to convert upstream cues to changes in cellular function. Effectors of classical H/K/NRAS are defined by RBD/RA domains which recognize the GTP-bound conformation of these GTPases, yet the specificity of RBD/RAs for over 160 RAS superfamily proteins remains poorly explored. We have systematically mapped interactions between BRAF and four RASSF effectors, the largest family of RA-containing proteins, with all RAS, RHO and ARF small GTPases. 39 validated complexes reveal plasticity in RASSF binding, while BRAF demonstrates tight specificity for classical H/K/NRAS. Complex between RASSF5 and diverse RAS GTPases at the plasma membrane can activate Hippo signalling and sequester YAP in the cytosol. RASSF8 undergoes liquid-liquid phase separation and resides in YAP-associated membraneless condensates, which also engage several RAS and RHO GTPases. The poorly studied RASSF3 has been identified as a first potential effector of mitochondrial MIRO proteins, and its co-expression with these GTPases impacts mitochondria and peroxisome distribution. These data reveal the complex nature of GTPase-effector interactions and show their systematic elucidation can reveal completely novel and biologically relevant cellular processes.

Comparative assessment of external apical root resorption between subjects treated with clear aligners and fixed orthodontic appliances: A systematic review and meta-analysis.

This review aims to collate and analyze the existing evidence on the comparison of external apical root resorption (EARR) in subjects treated with clear aligners (CAs) and fixed appliances (FA). An electronic search was conducted in six databases for articles published in all languages until July 2023. Studies that evaluated EARR in subjects treated with CAs and FAs were included. The RoB 2 tool for RCTs and the ROBINS-I tool for non-randomized studies were used to analyze the risk of bias (ROB). A random effects meta-analysis was performed to assess EARR extent in maxillary and mandibular anterior teeth for subjects treated with CAs and FAs. Ten studies (eight retrospective, one RCT, and one CCT) were included in this review, out of which six studies reported a moderate ROB, one reported a serious ROB, and three reported a low ROB on qualitative analysis. The quantitative analysis of six studies revealed a significant intergroup difference (P<0.05) in the mean EARR for maxillary central (SMD=-0.62, P<0.00001) and lateral incisors (SMD=-0.47, P=0.01) with a moderate heterogeneity (I2=56%), as well as the mandibular central incisors (SMD=-0.27, P=0.04) with high heterogeneity (I2=79%). EARR was lower in subjects treated with CAs than FAs. A moderate quality of the available evidence suggests that EARR was less evident in subjects treated with CAs when compared with FAs.

Lid Margin Microbiome in Stevens-Johnson Syndrome Patients With Lid Margin Keratinization and Severe Dry Eye Disease.

Purpose: The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD). Methods: Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12 years) and 10 patients with chronic SJS (mean age = 31.2 ± 14 years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin. Results: All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome. Conclusions: Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.

Feasibility of online learning among Indian students of dentistry during the CoVid-19 outbreak.

Even though there were several online dentistry academic programs available, the pandemic accelerated the development of e-learning processes and presented unprecedented obstacles to dental education. The pandemic has given rise to a technology-powered teaching style that replaced the centuries-old chalk-talk method. However, because it was a quick change, it had flaws and limitations and has caused turmoil and confusion among many educational teams, particularly in the academic sector. As a necessary consequence, this study is performed to evaluate undergraduate dental students' lived experiences, as well as their capability, willingness and frame of mind for the adoption of online teaching and learning approaches as part of blended learning. Hence, the use of online tutorials should be an effective method of providing meaningful insights for undergraduate dental students.

Neuroinflammation and acetylcholinesterase inhibition potentials of acyclic monoterpenoids isolated from Cymbopogon distans (Nees ex Steud.) Will. Watson.

Cymbopogon distans (Nees ex Steud.) Will. Watson (Poaceae) is a promising aromatic plant distributed in the Himalayas. In this study, five acyclic monoterpenoids, namely geranyl acetate (RS1), neral (RS2), geranial (RS3), citral (RS4) and geraniol (RS5) were isolated from the essential oil of C. distans. The isolated compounds were tested for in-vitro neuroinflammation inhibitory potential in LPS-stimulated BV2 microglial cells. RS1-RS4 exhibited significant neuroinflammation inhibition without any cytotoxic effect at the dose of 10 µM. RS4, the most active anti-neuroinflammatory compound (TNF-α 31.48 ± 1.00%; IL-6 24.02 ± 0.63%; IL-1ß 42.15 ± 1.76%) was also able to inhibit acetylcholinesterase (AChE) in a dose-dependent manner. The results showed that RS4 (an isomeric mixture of neral and geranial) has the potential to inhibit neuroinflammation and AChE, which are the biomarkers of neurodegenerative disorders.

Sustainable Synthesis of Novel Green-Based Nanoparticles for Therapeutic Interventions and Environmental Remediation.

The advancement in nanotechnology has completely revolutionized various fields, including pharmaceutical sciences, and streamlined the potential therapeutic of many diseases that endanger human life. The synthesis of green nanoparticles by biological processes is an aspect of the newly emerging scientific field known as "green nanotechnology". Due to their safe, eco-friendly, nontoxic nature, green synthesis tools are better suited to produce nanoparticles between 1 and 100 nm. Nanoformulation of different types of nanoparticles has been made possible by using green production techniques and commercially feasible novel precursors, such as seed extracts, algae, and fungi, that act as potent reducing, capping, and stabilizing agents. In addition to this, the biofunctionalization of nanoparticles has also broadened its horizon in the field of environmental remediation and various novel therapeutic innovations including wound healing, antimicrobial, anticancer, and nano biosensing. However, the major challenge pertaining to green nanotechnology is the agglomeration of nanoparticles that may alter the surface topology, which can affect biological physiology, thereby contributing to system toxicity. Therefore, a thorough grasp of nanoparticle toxicity and biocompatibility is required to harness the applications of nanotechnology in therapeutics.

Thirteen Indians with camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome (MIM# 208250) is a rare monogenic disorder, characterized by early onset of camptodactyly, progressive coxa vara, bilateral arthropathy and constrictive pericarditis. The syndrome is caused by biallelic loss-of-function variants in PRG4 . Deficiency of PRG4 results in progressive worsening of joint deformity with age. Thirteen individuals with CACP syndrome from eight consanguineous Indian families were evaluated. We used exome sequencing to elucidate disease-causing variants in all the probands. These variants were further validated and segregated by Sanger sequencing, confirming the diagnosis of CACP syndrome in them. Seven females and six males aged 2-23 years were studied. Camptodactyly (13/13), coxa vara (11/13), short femoral neck (11/13) and arthritis in large joints (12/13) [wrists (11/13), ankle (11/13), elbow (10/13) and knee (10/13)] were observed commonly. Five novel disease-causing variants (c.3636G>T, c.1935del, c.1134dup, c.1699del and c.962T>A) and two previously reported variants (c.1910_1911del and c.2816_2817del) were identified in homozygous state in PRG4 . We describe the phenotype and mutations in one of the large cohorts of patients with CACP syndrome, from India.

Biallelic loss of function variants in FUZ result in an orofaciodigital syndrome.

Orofaciodigital syndrome is a distinctive subtype of skeletal ciliopathies. Disease-causing variants in the genes encoding the CPLANE complex result in a wide variety of skeletal dysplasia with disturbed ciliary functions. The phenotypic spectrum includes orofaciodigital syndrome and short rib polydactyly syndrome. FUZ, as a part of the CPLANE complex, is involved in intraflagellar vesicular trafficking within primary cilia. Previously, the variants, c.98_111+9del and c.851G>T in FUZ were identified in two individuals with a skeletal ciliopathy, manifesting digital anomalies (polydactyly, syndactyly), orofacial cleft, short ribs and cardiac defects. Here, we present two novel variants, c.601G>A and c.625_636del in biallelic state, in two additional subjects exhibiting phenotypic overlap with the previously reported cases. Our findings underscore the association between biallelic loss of function variants in FUZ and skeletal ciliopathy akin to orofaciodigital syndrome.

Trichiasis in cicatricial ocular surface disease: a multi-center comparison of electroepilation versus eyelash resection outcomes.

PURPOSE: To evaluate the outcomes of trichiasis (excluding entropion) management in non-trachomatous cicatricial ocular surface diseases. METHODS: This is a multicenter, retrospective study of 59 patients with trichiasis who were managed using two different techniques: electroepilation using radiofrequency (RF) cautery and eyelash resection. The assessed outcomes were residual trichiasis at 6 weeks, 6, and 12 months of follow-up and the number of procedures needed. RESULTS: 41 patients (90 eyelids) underwent electroepilation, and 18 (41 eyelids) were managed with eyelash resection. All patients belonged to either Indian or Japanese ethnicity. Most patients in both groups had Stevens-Johnson Syndrome (63.4% vs. 88.9%). The mean age (43.2 vs. 46 years), disease duration (122 vs. 192.4 months), median trichiasis grade (2 vs. 2), and involvement of upper eyelids (53/90 vs. 23/41) were similar in the two groups. At six weeks, 48.9% of eyelids that underwent electroepilation had no trichiasis, and recurrences were managed with repeat electroepilation (6 eyelids) and mucous membrane grafting (10 eyelids), and 35 eyelids opted for manual epilation, giving 67.8% success at a mean follow-up of 20 months. The eyelash resection group had 75.6% success at 6 months, and recurrences were managed using lid splitting and eyelash resection, resulting in 100% success at a mean follow-up of 79 months. More interventions were needed in the electroepilation group compared to eyelash resection. CONCLUSION: Eyelash resection of the trichiatic eyelashes achieves a better success rate than electroepilation in cicatricial ocular surface disorders. Following electroepilation, one needs multiple interventions to resolve trichiasis.