A broadly neutralizing monoclonal antibody overcomes the mutational landscape of emerging SARS-CoV-2 variants of concern.

The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.

Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma.

Cross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses. In recent years, highly potent and/or broadly neutralizing human monoclonal antibodies (bnAbs) that are generated in chronic HIV-1 infections have been defined. These bnAbs exhibit atypical features such as extensive somatic hypermutations, long complementary determining region (CDR) lengths, tyrosine sulfation and presence of insertions/deletions, enabling them to effectively neutralize diverse HIV-1 viruses despite extensive variations within the core epitopes they recognize. As some of the HIV-1 bnAbs have evolved to recognize the dense viral glycans and cross-reactive epitopes (CREs), we assessed if these bnAbs cross-react with SARS-CoV-2. Several HIV-1 bnAbs showed cross-reactivity with SARS-CoV-2 while one HIV-1 CD4 binding site bnAb, N6, neutralized SARS-CoV-2. Furthermore, neutralizing plasma antibodies of chronically HIV-1 infected children showed cross neutralizing activity against SARS-CoV-2 pseudoviruses. Collectively, our observations suggest that human monoclonal antibodies tolerating extensive epitope variability can be leveraged to neutralize pathogens with related antigenic profile.

A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex.

The envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is the sole target of broadly neutralizing antibodies (bnAbs). Several mechanisms, such as the acquisition of mutations, variability of the loop length, and alterations in the glycan pattern, are employed by the virus to shield neutralizing epitopes on Env to sustain survival and infectivity within the host. The identification of mutations that lead to viral evasion of the host immune response is essential for the optimization and engineering of Env-based trimeric immunogens. Here, we report a rare leucine-to-phenylalanine escape mutation (L184F) at the base of hypervariable loop 2 (population frequency of 0.0045%) in a 9-month-old perinatally HIV-1-infected infant broad neutralizer. The L184F mutation altered the trimer conformation by modulating intramolecular interactions stabilizing the trimer apex and led to viral escape from autologous plasma bnAbs and known N160 glycan-targeted bnAbs. The L184F amino acid change led to the acquisition of a relatively open trimeric conformation, often associated with tier 1 HIV-1 isolates and increased susceptibility to neutralization by polyclonal plasma antibodies of weak neutralizers. While there was no impact of the L184F mutation on free virus transmission, a reduction in cell-to-cell transmission was observed. In conclusion, we report a naturally selected viral mutation, L184F, that influenced a change in the conformation of the Env trimer apex as a mechanism of escape from contemporaneous plasma V2 apex-targeted nAbs. Further studies should be undertaken to define viral mutations acquired during natural infection, to escape selection pressure exerted by bnAbs, to inform vaccine design and bnAb-based therapeutic strategies.IMPORTANCE The design of HIV-1 envelope-based immunogens capable of eliciting broadly neutralizing antibodies (bnAbs) is currently under active research. Some of the most potent bnAbs target the quaternary epitope at the V2 apex of the HIV-1 Env trimer. By studying naturally circulating viruses from a perinatally HIV-1-infected infant with plasma neutralizing antibodies targeted to the V2 apex, we identified a rare leucine-to-phenylalanine substitution, in two out of six functional viral clones, that destabilized the trimer apex. This single-amino-acid alteration impaired the interprotomeric interactions that stabilize the trimer apex, resulting in an open trimer conformation and escape from broadly neutralizing autologous plasma antibodies and known V2 apex-directed bnAbs, thereby favoring viral evasion of the early bnAb response of the infected host. Defining the mechanisms by which naturally occurring viral mutations influence the sensitivity of HIV-1 to bnAbs will provide information for the development of vaccines and bnAbs as anti-HIV-1 reagents.

An HIV-1 Broadly Neutralizing Antibody from a Clade C-Infected Pediatric Elite Neutralizer Potently Neutralizes the Contemporaneous and Autologous Evolving Viruses.

Broadly neutralizing antibodies (bNAbs) have demonstrated protective effects against HIV-1 in primate studies and recent human clinical trials. Elite neutralizers are potential candidates for isolation of HIV-1 bNAbs. The coexistence of bNAbs such as BG18 with neutralization-susceptible autologous viruses in an HIV-1-infected adult elite controller has been suggested to control viremia. Disease progression is faster in HIV-1-infected children than in adults. Plasma bNAbs with multiple epitope specificities are developed in HIV-1 chronically infected children with more potency and breadth than in adults. Therefore, we evaluated the specificity of plasma neutralizing antibodies of an antiretroviral-naive HIV-1 clade C chronically infected pediatric elite neutralizer, AIIMS_330. The plasma antibodies showed broad and potent HIV-1 neutralizing activity with >87% (29/33) breadth, a median inhibitory dilution (ID50) value of 1,246, and presence of N160 and N332 supersite-dependent HIV-1 bNAbs. The sorting of BG505.SOSIP.664.C2 T332N gp140 HIV-1 antigen-specific single B cells of AIIMS_330 resulted in the isolation of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01. The AIIMS-P01 neutralized 67% of HIV-1 cross-clade viruses, exhibited substantial indels despite limited somatic hypermutations, interacted with native-like HIV-1 trimer as observed in negative stain electron microscopy, and demonstrated high binding affinity. In addition, AIIMS-P01 neutralized the coexisting and evolving autologous viruses, suggesting the coexistence of vulnerable autologous viruses and HIV-1 bNAbs in the AIIMS_330 pediatric elite neutralizer. Such pediatric elite neutralizers can serve as potential candidates for isolation of novel HIV-1 pediatric bNAbs and for understanding the coevolution of virus and host immune response.IMPORTANCE More than 50% of the HIV-1 infections globally are caused by clade C viruses. To date, there is no effective vaccine to prevent HIV-1 infection. Based on the structural information of the currently available HIV-1 bNAbs, attempts are under way to design immunogens that can elicit correlates of protection upon vaccination. Here, we report the isolation and characterization of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01, from a clade C chronically infected pediatric elite neutralizer. The N332 supersite is an important epitope and is one of the current HIV-1 vaccine targets. AIIMS-P01 potently neutralized the contemporaneous and autologous evolving viruses and exhibited substantial indels despite low somatic hypermutations. Taken together with the information on infant bNAbs, further isolation and characterization of bNAbs contributing to the plasma breadth in HIV-1 chronically infected children may help provide a better understanding of their role in controlling HIV-1 infection.

Viral Characteristics Associated with Maintenance of Elite Neutralizing Activity in Chronically HIV-1 Clade C-Infected Monozygotic Pediatric Twins.

Broad and potent neutralizing antibodies (bnAbs) with multiple epitope specificities evolve in HIV-1-infected children. Herein, we studied two antiretroviral-naive chronically HIV-1 clade C-infected monozygotic pediatric twins, AIIMS_329 and AIIMS_330, with potent plasma bnAbs. Elite plasma neutralizing activity was observed since the initial sampling at 78 months of age in AIIMS_330 and persisted throughout, while in AIIMS_329 it was seen at 90 months of age, after which the potency decreased over time. We evaluated potential viral characteristics associated with the varied immune profiles by generating single genome-amplified pseudoviruses. The AIIMS_329 viruses generated from the 90-month time point were neutralization sensitive to bnAbs and contemporaneous plasma antibodies, while viruses from the 112-month and 117-month time points were resistant to most bnAbs and contemporaneous plasma. AIIMS_329 viruses developed resistance to plasma neutralizing antibodies (nAbs) plausibly by N160 glycan loss and V1 and V4 loop lengthening. The viruses generated from AIIMS_330 (at 90 and 117 months) showed varied susceptibility to bnAbs and autologous contemporaneous plasma antibodies, while the viruses of the 112-month time point, at which the plasma nAb specificities mapped to the V2 glycan, V3 glycan, and CD4 binding site (CD4bs), were resistant to contemporaneous plasma antibodies as well as to most bnAbs. Chimeric viruses were constructed from 90-month-time-point PG9-sensitive AIIMS_329 and AIIMS_330 viruses with swapped V1V2 regions of their respective evolved viruses (at 112 and 117 months), which led to higher resistance to neutralization by PG9 and autologous plasma antibodies. We observed the evolution of a viral pool in the AIIMS_330 donor comprising plasma antibody neutralization-sensitive or -resistant diverse autologous viruses that may have contributed to the development and maintenance of elite neutralizing activity.IMPORTANCE Herein, we report the longitudinal development of bnAbs in a pair of chronically HIV-1 clade C-infected monozygotic pediatric twins, AIIMS_329 and AIIMS_330, who acquired the infection by vertical transmission. The plasma from both donors, sharing a similar genetic makeup and infecting virus, showed the evolvement of bnAbs targeting common epitopes in the V2 and V3 regions of the envelope, suggesting that bnAb development in these twins may perhaps be determined by specific sequences in the shared virus that can guide the development of immunogens aimed at eliciting V2 and V3 bNAbs. Characterization of the neutralization-sensitive and -resistant viruses coevolving with bNAbs in the contemporaneous AIIMS_330 plasma provides information toward understanding the viral alterations that may have contributed to the development of resistance to bnAbs. Further longitudinal studies in more monozygotic and dizygotic twin pairs will help in delineating the role of host and viral factors that may contribute to the development of bnAbs.

The immediate impact of mandatory helmet law on maxillo-facial trauma: A comparative study in a major trauma center, Uttar Pradesh.

Aim: To analyze the effect of the mandatory helmet rule in helmet usage among motorcycle riders and on facial trauma and to determine the significance of difference in the possibility of facial trauma between the helmeted and non-helmeted motorcycle riders. Setting and Design: A retrospective comparative study conducted in a major trauma center at Uttar Pradesh. Material and Method: Data for the present study was obtained from records of the Emergency Department of Trauma Center, for a period of two months before and after the implementation of The Motor Vehicles Act in UP. The study included patients with a history of non-fatal motorcycle accidents who sustained facial injuries regardless of the presence of injuries to other areas of the body during the study period. Information regarding helmet usage during the accident was also recorded. The results were compared between the pre-law period and post-law period. Statistical Analysis Used: Sample t-test was applied to find the level of significance. Results: Out of 219 injured patients, 152 (69.40%) subjects were not wearing helmets, whereas only 67 (30.59%) subjects were wearing helmets. It was observed that around 68.18% of people stated wearing helmets after law implementation with a statistical significance (P value < 0.05). Conclusion: Our study shows that the mandatory helmet rule with elevated penalty rates has significantly increased the usage of helmet among the motorcycle riders, and it also proves that the possibility of facial trauma is significantly higher in non-helmeted riders when compared to helmeted riders.

Technology in farming: Unleashing farmers' behavioral intention for the adoption of agriculture 5.0.

The agriculture sector has undergone a remarkable revolution known as Agriculture 5.0 (Ag 5.0), emphasizing digital technology to boost efficiency and profitability of farm business. However, little is known about farmers' behavioral intension to adopt Ag 5.0. In this study we examine factors influencing farmer's behavioral intension for Agriculture 5.0, identify implementation obstacles and provide managerial solutions to promote Ag 5.0 in Madhesh Province, Nepal, using the Technology Acceptance Model (TAM) and Structural Equation Model (SEM). We tested total of 20 different hypotheses. Primary data were collected from 271 farmers across 9 municipalities in Saptari District, Nepal. The study reveals that technology anxiety [(ß = 0.101, p<0.01); (ß = 0.188, p<0.01)], self-efficacy [(ß = 0.312, p<0.01, (ß = 0.170, p<0.05)] and social influence [(ß = 0.411, p<0.01), (ß = 0.170, p<0.05)] significantly impact the perceived usefulness as well as perceived ease of use, respectively. Individual innovativeness also affects the perceived usefulness (ß = 0.004, p<0.05) and perceived ease of use (ß = 0.281, p<0.01). Moreover, the study found that attitude towards using Ag 5.0 is significantly influenced by perceived usefulness (ß = 0.083, p<0.10) and ease of use (ß = 0.189, p<0.01), which, in turn, affects the intention to use Ag 5.0 (ß = 0.858, p<0.01). Farmers perceive training programs, government assistance, and subsidies as helpful in overcoming challenges associated with adopting Ag 5.0. This study provides valuable insights for policymakers, development partners, and farmers' organizations, enabling them to understand the factors influencing the readiness for Ag 5.0 adoption in Nepal.

Bipaddled Pectoralis Major Myocutaneous Flap in Complex Oral Cancer Defects- A Single Center Experience with Quality of Life Assessment.

Introduction: Advanced stage malignancies of oral cavity commonly result in complex full thickness defects with subsequent functional and aesthetic loss. Through this article we describe our center's experience in reconstruction of such defects with bipaddled pectoralis myocutaneous (PMMC) flap through an immediate, single-staged procedure. Materials And Methods: The study included a total of 54 patients who underwent composite resection and neck dissection followed by reconstruction of the defect with bipaddled PMMC flap. All patients were followed up post-operatively for 1 year and were monitored for flap and donor site related complications. Using University of Washington Quality of life v4 questionnaire (UW-QOL4), we assessed the QOL of 54 patients. The mean scores were compared to other similar studies. Results: The overall complication rate was 66.6%, whereas, 33.3% patients had no complications. The most common complication was wound dehiscence seen in 31.5% of cases in the recipient site and 12.9% in the donor site. Other complications were seroma, hematoma, plate exposure, orocutaneous fistula etc. Around 73.7% patients reported a good, very good or outstanding overall quality of life in the post-operative period. The mean composite QOL score was 65.84. Our study showed comparable domains of pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function and taste with other similar studies. Conclusion: Bipaddled PMMC flap proves to be a considerable alternative for microvascular free flaps in reconstruction of full-thickness defects of oral cavity owing to its reliable blood supply, accessibility, easier harvesting technique, cost effectiveness, high success rate and acceptable quality of life. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03324-6.

Effects of curcumin on oral cancer at molecular level: A systematic review.

This systematic review mainly focuses on the effects of curcumin on oral cancer cells at the molecular level and summarizes the results of the studies. We searched and analyzed various databases such as Pub Med, ProQuest, Google Scholar, Science Direct, and Scopus. Searches were conducted from 2006 to 2021. This systematic review evaluated various effects of curcumin on oral cancer at the molecular level. All the studies related to the effects of curcumin on oral cancer, both in-vivo and in-vitro, were included. After abstract and text screening a total of 13 articles were finally selected for the study based on the inclusion and exclusion criteria. All most all the included studies reported that after treating the cell lines with curcumin there is a reduction in cell proliferation and cell growth, analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Curcumin also induces S phase cell cycle arrest and also prevents Tregs migration. The curcumin reverses the process of epithelial mesenchymal transition (EMT) back to mesenchymal epithelial transition (MET). From this review, it is concluded that curcumin inhibited proliferation, migration, invasion, and metastasis, and induced apoptosis via modulating multiple signaling pathways in oral cancer cell lines. But further clinical trials are needed for a detailed evaluation of the effects of curcumin on patients with oral cancer.

Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.

Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline-encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV-2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.

Management of Maxillary Sagittal Fracture by using Pre-activated Rapid Maxillary Expansion (RME).

Introduction: Different techniques of the management of sagittal maxillary fractures have been described with different advantages and disadvantages. We herein present our experience and results of managing these cases by reversing pre-activated maxillary expanders and evaluation of its efficacy. Patient and Methods: A prospective study was conducted from April 2016 to February 2020 including all the patients managed for sagittal palatal fractures using the modified technique. The patients were evaluated for healing, occlusion and complications. Results: A total of five patients with sagittal palatal fracture were managed. The mean Glasgow Coma (GCS) score and injury severity score (ISS) of patients were 11.6 ± 2.4 and 15.2 ± 4.3, respectively. Both had a significant strong negative correlation with a correlation coefficient of - 0.889 (p = 0.44). The median duration for initiating the treatment for facial fractures was 2 days (range 2-12 days). All patients achieved satisfactory outcomes and tolerated this technique well. No obvious complications were found. Conclusion: This method could produce enough transversal force to reduce fractured fragments and then serve as an external fixator to maintain stability for bony healing.

Autoreconstruction of the tongue in case of extensive verrucous carcinoma.

Tongue reconstruction can be simple to complex depending on the size of the defect. Reconstruction of medium-to-large size defect is technically demanding to achieve better esthetic and functional outcome. There are various options in the reconstruction of tongue defect when it comes to the type of flap. Any type of flap has its own advantages and disadvantages. Local flaps seem to be the best option, as it avoids secondary donor site morbidity and has similar tissue characteristics as native tissue, therefore provides better esthetic and functional results. This case report illustrates a case of tongue reconstruction that was performed with the help of tongue base island flap after wide local excision of verrucous carcinoma, which provided us with excellent results.

Mango-shaped Bi-paddled pectoralis major myocutaneous flap reconstruction for large full-thickness defects post resection of squamous cell carcinoma of oral cavity: An analysis of 232 cases.

Objectives: The objective of the study was to examine the feasibility of bi-paddled pectoralis major myocutaneous (PMMC) flap reconstruction in patient undergoing full thickness composite resection. Materials and Methods: Inclusion criteria: The subjects chosen were patients with clinically T4A squamous cell carcinoma of buccal mucosa, lower alveolus, and maxilla in with skin involvement. Patients required a full-thickness composite resection of intraoral lesion, bone (mandibular segment and/or maxilla), and overlying involved skin and had modified radical neck dissection. Exclusion criteria: Patients not requiring full thickness composite resection including skin. Patients were observed postoperatively for early and late postoperative complications, starting of oral feeding, post-operative trismus, and dysphagia during subsequent follow-up and cosmetic outcome. Results: Overall, the complication rate was 33.8% out of which only 7.8% required major re-surgery with second flap reconstruction. This is comparable with other large series of PMMC flap. Clavien-Dindo Grade I complications were seen in 9.5%, Grade II in 69.7%, Grade IIIA in 13.4%, and Grade IIIB in 7.45% of patients. Full-thickness partial flap necrosis included necrosis of either the external or the internal skin paddle. There were 15 cases - 6.5% of full thickness external paddle necrosis. These were mostly in patients with bite composite resections and having a larger random fasciocutaneous distal component of the flap without underlying muscle. Furthermore, 40% of these patients were females. In females, the flap necrosis comprised 4 of the 12 patients (33.33%). Conclusion: Pectoralis major mycocutaneous flap has been a boon to reconstruction of the oral cavity post its inception. In case of locally advanced squamous cell carcinomas of the oral cavity, in many instances, there is a clinically significant cervical lymph nodal spread vessels post mandating a comprehensive lymph node dissection. PMMC flap provides a robust well vascularized muscular cover to the cervical vessels poststernocleidomastoid excision.

Systematic Review of Intra Parotid Facial Nerve Schwannoma and a Case Report.

To evaluate the clinico-epidemiological aspects, pathological features, diagnostic methods, management protocol and functional outcome of the intra-parotid facial nerve schwannoma (IFNS) and to present a case report on intra parotid facial nerve schwannoma. PubMed, ProQuest, Google scholar, Science direct and Scopus were screened for studies. Article selection and data extraction was done by one investigator and other investigator confirmed its accuracy. After abstract and text screening a total of 69 articles were finally selected for the study with the inclusion and exclusion criteria of the systematic review as per PRISMA guidelines. With addition of one case reported to our department. The mean age of diagnosis was 43 ± 16 years with a slight female predominance. The mean duration of the tumour was 29.5 months and the mean size of the tumour on initial diagnosis was 3.6 ± 1.67 cm. Pleomorphic adenoma was the primary diagnosis in 44 cases. Superficial parotidectomy was done in 64 cases followed by resection in 47 cases. Reconstructive treatment was carried out by an end-to-end anastomosis in 3 patients and by facial-hypoglossal anastomosis in 16 patients, GAN cable grafting in 5 patients, a greater auricular nerve graft was done in18 patients and end-to-side interposed sural nerve graft in 8 patients. The type D tumours are treated by extended resection of the facial nerve, which is difficult to reconstruct and also employs a nerve graft that does not often give acceptable recovery of facial function. Facial nerve schwannomas being a rare entity poses a dilemma in diagnosis and management. Managing the lesions is also difficult as intraoperative adherence to the nerve makes a tumour free margin difficult without sacrificing the nerve. At present there is no consensus regarding the management of various types of intra-parotid facial nerve shwannoma.

Circadian desynchronization in pregnancy of Golden hamster following long time light exposure: Involvement of Akt/FoxO1 pathway.

Coordination between central and peripheral reproductive clocks in females is poorly understood. Long light is having a hazardous effect on reproductive health. Hence, explored the effect of long-time light exposure (LLD; 16L:8D) on the central and peripheral reproductive (ovary and uterus) clock genes (Bmal1, Clock, Per1, Per2, Cry1 and Cry2) and its downstream regulators (Aanat, Egf, Cx26, Cx43, ERα, pAktS-473, pAktT-308, pFoxO1T-24, 14-3-3, HoxA10, HoxA11 and Pibf) expression in non-pregnant and pregnant Golden hamster. Young adult Golden hamsters were exposed to LLD for 30 days and then were mated. We observed that LLD exposure increased the thickness of the endometrium and reduced myometrium thickness, resembling uterine adenomyosis. In non-pregnant females LLD altered the expressions of clock genes in suprachiasmatic nuclei (SCN), ovary and the uterus along with serum estradiol rhythm. LLD upregulated Egf and downregulated Aanat, Cx26, and Cx43 mRNA levels in uterus. LLD upregulated Akt/FoxO1 phosphorylation and 14-3-3 expressions in the uterus of nonpregnant females. LLD exposure to pregnant females lowered serum progesterone, Aanat, Pibf, Hoxa10, and Hoxa11 mRNA expressions on D4 (peri-implantation) and D8 (post-implantation) resulting in a low implantation rate on D8 (post-implantation). Hence it is evident that the frequent pregnancy anomalies noted under a long light schedule might be due to desynchronization in Aanat, Pibf, Hoxa10, and Hoxa11 as well as the central and peripheral clock genes (Bmal1, Clock, Per1, Per2, Cry1 and Cry2). LLD exposure desynchronized the central and peripheral reproductive clock affecting uterine physiology via Akt/FoxO1 pathway in Golden hamsters. Thus, LLD is a risk factor for female reproductive health and fertility.

En Block Versus Separate Management of Cervical Nodes in Tongue and Floor of the Mouth Cancers- Is There a Difference? An Analysis of 85 Cases in a Tertiary Care Institute.

To evaluate difference in local recurrence, regional (neck) recurrence as well as distant metastases between cases operated with en-block excision of primary cancer and neck nodes versus their separate removal, in squamous cell carcinomas of anterior 2/3 of tongue and floor of the mouth. A total 85 patients of cT1-T4a N0-N2b of carcinoma anterior 2/3 of tongue and floor of mouth were evaluated. Amongst these patients 39 cases of in-continuity en-block neck dissection and 46 cases of discontinuous neck dissection were evaluated for post-operative complications as well as oncological outcome for a follow up period of 3 years. Patient population was similar in both groups with tongue cancers being the commonest site and tobacco being the most common addiction. Primary site hematoma was seen more in the in-continuity en-block neck dissection group with a p-value of 0.0276, which was statistically significant. Post-operative oro-cutaneous fistula occurred more in in-continuity enblock neck dissection as compared to discontinuous neck dissection, but the difference was not statistically significant. Local recurrence rate was significantly more in cases of discontinuous neck dissection (19.565) as compared to in-continuity en-block neck dissection (5.12%) with a p-Value 0.0481. A statistically non-significant but higher loco-regional recurrence was observed in cases of discontinuous neck dissection as compared to cases of in-continuity en-block neck dissection (10.56% vs 2.56). In the present study recurrence-free survival RFS 3 year in cases of en-block in-continuity neck dissection (84.06%) cases as compared to discontinuous neck dissection cases (63.04%) with p Value 0.025698. In-continuity en-block in continuity neck dissection has lower loco-regional recurrence and may impact overall distant metastases. Though early postoperative complications are more in in-continuity en-block in continuity neck dissection as compared to discontinuous neck dissection, most are managed conservatively. Further studies with a larger sample size are needed to evaluate its outcome in a comprehensive manner.

Temporomandibular joint ankylosis: A tertiary center-based epidemiological study.

INTRODUCTION: Limitation of mouth opening can be caused by bony or fibrous ankylosis of the temporomandibular joint (TMJ) as a sequel to trauma, infection, or autoimmune diseases. The incidence of TMJ ankylosis differs significantly in different parts of the world. The purpose of this study was to analyze the etiological incidence of TMJ ankylosis at our tertiary-level center, which covers a huge population from parts of Bihar and eastern Uttar Pradesh. MATERIALS AND METHODS: This study was conducted from July 2016 to April 2019, and a total of 1607 children were screened in the duration of 33 months. Participants were included in this study as per the inclusion and exclusion criteria. RESULTS: After screening of the 1607 children, 128 TMJ ankylosis cases were identified. Out of the 128 cases of TMJ ankylosis, 33 cases were bilateral and 95 cases were unilateral (48 left sided and 47 right sided). Most of the patients (83.5%) were in the 10-15-year-old age group (mean age was 12.1 ± 2.83 years). There was a female preponderance, and the male-to-female ratio was 7:10. Overall, the most common cause of ankylosis was found to be childhood trauma. CONCLUSION: The major etiologic factor of TMJ ankylosis was found to be birth/childhood trauma. TMJ ankylosis cases were detected in significant numbers in this study. This increased prevalence may be due to the lack of knowledge about this pathological entity among the general population and health-care professionals at primary level, which leads to poor initial management.

Evaluation of Arthrocentesis with and Without Platelet-Rich Plasma in the Management of Internal Derangement of Temporomandibular Joint: A Randomized Controlled Trial.

PURPOSE: The purpose of this study was to compare the efficacy of intra-articular injection of platelet-rich plasma after arthrocentesis versus arthrocentesis alone as a treatment modality in patients with internal derangement of temporomandibular joint. METHODS: Twenty-four patients suffering from internal derangement of temporomandibular joint were included in the study. The patients were randomly divided into two groups as follows-twelve patients underwent arthrocentesis followed by intra-articular injection of platelet-rich plasma (study group) and the other twelve were treated by arthrocentesis alone (control group). Pain intensity was recorded on visual analogue scale (VAS); maximum mouth opening and joint sound were measured before and after intervention. The patients were clinically evaluated at the intervals of 1 month, 3 and 6 months subsequently. RESULTS: There was no statistically significant difference in all the parameters between the groups. Intra-group analysis showed statistically significant improvement in all the parameters. CONCLUSION: In both groups, improvement of pain, maximum mouth opening and TMJ sound were observed at all intervals, but there was no statistically significant improvement in arthrocentesis with PRP group when compared with arthrocentesis alone.

Temporalis myofascial flap in reconstruction of maxillary defect: A case series.

Ablative surgery of midface often leads to compromised aesthetics as well as function. Defects caused by ablative surgery need reconstruction that provides satisfactory results with minimal or no compromise in form and function. Various flaps can be used to reconstruct the maxillary defect. However, medium to large-sized defects can only be appropriately reconstructed using free or regional flaps. Moreover, as free flap reconstructions are tedious and require technique sensitive procedure whereas loco-regional flaps are versatile and more predictable. Temporalis myofascial flap (TMF) seems to be one of the best options among all other regional flaps as it has a reliable blood supply, adequate bulk and its anatomical location is close to primary defect.

Broadly neutralizing plasma antibodies effective against autologous circulating viruses in infants with multivariant HIV-1 infection.

Broadly neutralizing antibodies (bnAbs) develop in a subset of HIV-1 infected individuals over 2-3 years of infection. Infected infants develop plasma bnAbs frequently and as early as 1-year post-infection suggesting factors governing bnAb induction in infants are distinct from adults. Understanding viral characteristics in infected infants with early bnAb responses will provide key information about antigenic triggers driving B cell maturation pathways towards induction of bnAbs. Herein, we evaluate the presence of plasma bnAbs in a cohort of 51 HIV-1 clade-C infected infants and identify viral factors associated with early bnAb responses. Plasma bnAbs targeting V2-apex on the env are predominant in infant elite and broad neutralizers. Circulating viral variants in infant elite neutralizers are susceptible to V2-apex bnAbs. In infant elite neutralizers, multivariant infection is associated with plasma bnAbs targeting diverse autologous viruses. Our data provides information supportive of polyvalent vaccination approaches capable of inducing V2-apex bnAbs against HIV-1.