Prosthetic Management of Flap-Related Complications Following Glossectomy in Locally Advanced Tongue Cancer.

Total glossectomy defects resulting from postoncologic resection are commonly reconstructed with locoregional or free flaps. However, effectively managing complications that may arise after reconstruction can be a significant challenge. We present a unique case series describing prosthetic management of flap-related complications following glossectomy in patients treated for locally advanced tongue cancer. Three patients underwent total glossectomy, neck dissection, reconstruction using free flap, and tracheostomy. Two patients developed an intraoral fistula located in the anterior region of the floor of the mouth. The third patient developed a flap failure requiring a second procedure using a pectoralis major myocutaneous flap for correction of the orocutaneous fistula that ultimately did not heal. Mandibular obturator prostheses lined with a soft liner were fabricated for all the patients, which helped reduce salivary incontinence and improve swallowing and speech. This case series highlights that a collaborative interdisciplinary team approach is crucial for optimizing postoperative function and outcomes when managing complications from reconstructive procedures.

Role and influence of growth factors on early osseointegration in animal jaw bone: A meta-analysis.

AIM: Growth factors (GFs) are polypeptides, which are intricately involved in the regulation of bone formation, preservation, and regeneration through gene expression. However, the role of these bioactive agents in osseointegration of dental implants has not been substantially proven. The objective of this systematic review (SR) and meta-analysis was to explore the effect of GFs on early osseointegration of dental implants in animal jaws. An attempt to decipher an adjunctive role of GFs in modulating predictable bone growth in peri-implant areas was done. MATERIALS AND METHODS: An electronic and manual search of different databases was performed. Only randomized controlled trials (RCTs) were included and reviewed. The risk of bias (ROB) of the selected studies was assessed using the SR Centre for Laboratory Animal Experimentation (Cochrane) tool. A meta-analysis was also performed to evaluate the different study characteristics quantitatively. STATISTICAL ANALYSIS USED: The total Weighted mean difference was evaluated using the Rev-Manv5.3 algorithm. Chi-square test and I2 test were done to assess the heterogeneity between the studies. RESULTS: Seven RCTs were included in the study. These were associated with a high ROB. The total weighted mean difference (WMD) of the percentage of bone-implant contact was 3.25% (95% confidence interval [CI] = 1.49%-6.03%; P = 0.001; I2 = 91%) between groups with and without exogenous application of GFs. The total WMD of the percentage of newly formed bone area was 4.48% (95% CI = 2.31%-5.90%; P < 0.00001, I2 = 84%). A high level of heterogeneity (P < 0.001 for Chi-square test; I 2>50 %) among comparable studies was observed. CONCLUSION: The ancillary application of external GFs exhibited evidence of early osseointegration, resulting in more predictable and faster results. However, a careful discernment of conclusions drawn from this SR is a must before conducting any human trials.

Fabrication of a bicomponent hybrid orbital prosthesis.

This clinical report describes the management of the retention of an orbital prosthesis in a patient with uncontrolled diabetes. The patient, who underwent left orbital exenteration subsequent to severe mucormycosis, posed a challenge for implant placement and for use of adhesives as a method of retention because of the high likelihood of reinfection. Inaccessibility to severe anatomic undercuts along with their arbitrary block out would have caused diminished retention. As a result, an orbital prosthesis composed of a digitally produced hollow conformer and traditionally produced silicone prosthesis was provided using 3-dimensional imaging and rapid prototyping, with optimum retention.

The Aspergillus fumigatus conidial melanin production is regulated by the bifunctional bHLH DevR and MADS-box RlmA transcription factors.

Melanins play a crucial role in defending organisms against external stressors. In several pathogenic fungi, including the human pathogen Aspergillus fumigatus, melanin production was shown to contribute to virulence. A. fumigatus produces two different types of melanins, i.e., pyomelanin and dihydroxynaphthalene (DHN)-melanin. DHN-melanin forms the gray-green pigment characteristic for conidia, playing an important role in immune evasion of conidia and thus for fungal virulence. The DHN-melanin biosynthesis pathway is encoded by six genes organized in a cluster with the polyketide synthase gene pksP as a core element. Here, cross-species promoter analysis identified specific DNA binding sites in the DHN-melanin biosynthesis genes pksP-arp1 intergenic region that can be recognized by bHLH and MADS-box transcriptional regulators. Independent deletion of two genes coding for the transcription factors DevR (bHLH) and RlmA (MADS-box) interfered with sporulation and reduced the expression of the DHN-melanin gene cluster. In vitro and in vivo experiments proved that these transcription factors cooperatively regulate pksP expression acting both as repressors and activators in a mutually exclusive manner. The dual role executed by each regulator depends on specific DNA motifs recognized in the pksP promoter region.

Lip prosthesis as a palliative care modality for a head and neck cancer patient-A case report.

The present case report describes the prosthetic management following partial loss of free-fibular osteocutaneous flap in an irradiated patient diagnosed with recurrent head and neck cancer. The patient presented with constant drooling of oral fluids due to an anatomically deficient lower lip. Salvage reconstructive surgery was not considered feasible due to past history of recurrence, multiple surgeries and radiotherapy, and financial constraints. An adhesive-retained interim silicone prosthesis was fabricated to alleviate the functional and psychosocial morbidity. The prosthesis served to restore the oro-facial seal to prevent constant drooling of oral fluids. It also aided in providing an excellent aesthetic solution to palliate the psychological suffering experienced by the patient due to lost facial contours.

Application of Polyvinyl chloride sheet as delayed surgical obturator in maxillectomy defects secondary to mucormycosis- A case series.

It was a great challenge for the prosthodontist to rehabilitate and sustain the prosthesis in patients with bilateral maxillectomy defects due to mucormycosis seen with Covid-19 during second wave in India. In such extensive defects there was difficulty in retaining the obturator due to the absence of soft tissue or anatomical undercuts, condition of existing dentition, retained inferior turbinates and limitation in taking retention from defect side during healing phase. In such extensive maxillectomy defects, retention, stability and support can be enhanced by maximum preservation of hard and soft tissues, skin grafting and removal of inferior turbinates to provide a larger surface area for stress distribution. But here, in this case series, maxillectomy defects with retained inferior turbinates presented a problem in retaining the obturator prosthesis due to limitation in taking retention from the defect side. The conventional method of fabrication of obturator using autopolymerizing acrylic failed in terms of weight of the prosthesis and in gaining retention from the defect side during healing phase. Therefore, thermoplastic vacuum pressed Polyvinyl chloride sheet (PVC) was used for fabrication of delayed surgical obturator due to many merits conferred by it. Its light weight, non porous nature, easy adaptability, patient comfort, efficient undercut engagement, hygienic nature makes it a good treatment option. The main cocern was to close oro-nasal communication to eliminate the need of nasogastric tube and to prevent nasal regurgitation. In all cases, patients were comfortable with the obturator prosthesis in terms of adaptation and function.

Medical Care for Newly Arrived Displaced Persons.

Medical Care for Displaced PersonsThe United Nations High Commissioner for Refugees reports that more than 100 million people have been forcibly displaced from their homes due to persecution, conflict, violence, and human rights violations. Displacement has profound health impacts. Here, Jain and colleagues review medical care for newly displaced persons.

The MAP kinase MpkA controls cell wall integrity, oxidative stress response, gliotoxin production and iron adaptation in Aspergillus fumigatus.

The saprophytic fungus Aspergillus fumigatus is the most important air-borne fungal pathogen. The cell wall of A. fumigatus has been studied intensively as a potential target for development of effective antifungal agents. A major role in maintaining cell wall integrity is played by the mitogen-activated protein kinase (MAPK) MpkA. To gain a comprehensive insight into this central signal transduction pathway, we performed a transcriptome analysis of the ΔmpkA mutant under standard and cell wall stress conditions. Besides genes involved in cell wall remodelling, protection against ROS and secondary metabolism such as gliotoxin, pyomelanin and pseurotin A, also genes involved in siderophore biosynthesis were regulated by MpkA. Consistently, northern and western blot analyses indicated that iron starvation triggers phosphorylation and thus activation of MpkA. Furthermore, localization studies indicated that MpkA accumulates in the nucleus under iron depletion. Hence, we report the first connection between a MAPK pathway and siderophore biosynthesis. The measurement of amino acid pools and of the pools of polyamines indicated that arginine was continuously converted into ornithine to fuel the siderophore pool in the ΔmpkA mutant strain. Based on our data, we propose that MpkA fine-tunes the balance between stress response and energy consuming cellular processes.

The effects of India's COVID-19 lockdown on critical non-COVID health care and outcomes: Evidence from dialysis patients.

India's COVID-19 lockdown, one of the most severe in the world, is widely believed to have disrupted critical non-COVID health services. However, linking these disruptions to effects on health outcomes has been difficult due to the lack of reliable, up-to-date health outcomes data. We identified all dialysis patients under a statewide health insurance program in Rajasthan, India (N = 2110), and conducted surveys to examine the effects of the lockdown on non-COVID care access and health outcomes. Post-lockdown mortality was our primary outcome and morbidity and hospitalization were secondary outcomes. 63% of patients experienced a disruption to their care. Transport barriers, hospital service disruptions, and difficulty obtaining medicines were the most common causes. We compared monthly mortality in the four months after the lockdown with pre-lockdown mortality trends, as well as with mortality trends for a similar cohort in the previous year. Mortality in May 2020, after a month of exposure to the lockdown, was 1.70 percentage points (95% CI 0.01-0.03) or 64% higher than in March 2020 and total excess mortality between April and July was estimated to be 22%. A 1SD increase in an index of care disruptions was associated with a 0.17SD (95% CI 0.13-0.22) increase in a morbidity index, a 3.1 percentage point (95% CI 0.012-0.051) increase in hospitalization, and a 2.1 percentage point (95% CI 0.00-0.04) increase in probability of death between May and July. Females, socioeconomically disadvantaged groups, and patients living far from the health system faced worse outcomes. The results highlight the unintended consequences of the lockdown on critical, life-saving non-COVID health services that must be taken into account in the implementation of future policy efforts to control the spread of pandemics.

A challenging journey of maxillofacial implants placement and rehabilitation in an irradiated exenterated socket.

Rehabilitation of a post-exenterated orbital defect is a necessity, to restore a patient's esthetic appearance and help overcome the associated psychosocial stigma. An implant supported prosthesis enjoys a better patient acceptance due to its superior retention and stability. This clinical report highlights the challenges faced in planning, designing and placement of maxillofacial implants in the supra-orbital rim of an exenterated socket post-radiotherapy along with the management of the unexpected complications which developed subsequently. Administration of hyperbaric oxygen therapy, fabrication of a digitally designed surgical guide to ensure predictable implant placement, selection of surface treated implants for better biomechanical anchorage, and a gentler surgical technique for recovery of irradiated hard and soft tissues were measures undertaken during the treatment phase. An effort has been made to point-out the fact that despite the various approaches adopted in an irradiated patient, success of implant placement in such a situation remains a challenge.

Comparative Evaluation of Load-Bearing Capacity and Fracture Analysis of PEEK and Zirconia Three-Unit Fixed Dental Prostheses: An In Vitro Study.

PURPOSE: The purpose of this exploratory in vitro study was to compare and evaluate the load-bearing capacity (LBC) of ceramic-veneered zirconia and composite-veneered polyetheretherketone (PEEK) three-unit fixed dental prostheses (FDPs) with and without thermocycling (TC). MATERIALS AND METHODS: The study included 40 samples of three-unit FDPs replacing mandibular first molars. The four groups included were: ceZIR (feldspathic ceramic-layered zirconia), ceZIR TC (feldspathic ceramic-layered thermocycled zirconia), cPEEK (composite-layered PEEK), and cPEEK TC (composite-layered thermocycled PEEK) (n = 10 per group). All frameworks were CAD/CAM milled. Ten PEEK and 10 zirconia samples were subjected to TC (6,000 cycles). All 40 FDP specimens were loaded by applying static load, using a universal testing machine. The maximum load required to fracture the specimens denoted the LBC. The comparison of LBC between the four groups was done by using two-way ANOVA with Tukey's post-hoc analysis (α = .05). RESULTS: There was no statistically significant difference between LBC of cPEEK and ceZIR (P > .001) without thermal aging. LBC values decreased considerably for thermally aged specimens. Statistically significant differences were observed between LBC of cPEEK TC and ceZIR TC (P < .001), cPEEK TC and cPEEK (P < .001), and ceZIR TC and ceZIR (P = .001). On fracture analysis, cPEEK showed delamination failures whereas ceZIR displayed catastrophic connector fractures. CONCLUSION: This comparative evaluation offers preliminary data highlighting substantial depreciation in the LBC of layered PEEK under simulated intraoral conditions, thus raising a question regarding the clinical longevity of layered PEEK multi-unit restorations. In contrast, feldspathic-layered zirconia can be suitable for use in posterior FDPs.

The relevance of extra-nodal natural killer/T-cell lymphoma to the oral health care providers- A clinical review with case report.

Lymphomas are the second most common malignancy in the oral cavity after squamous cell carcinoma. Non-specific clinical presentation of lymphoma mimics the other common oral pathologies thereby; delaying its diagnosis, ensuing definitive treatment, and leading to a guarded prognosis. The present clinical review and accompanying case report highlights the clinical presentation, diagnostic challenges, progression, manifestations, and holistic management of a rare extra-nodal, nasal variant of Natural Killer T-cell lymphoma and underscores the importance of interdisciplinary coordination in the overall management of this aggressive tumor.

COVID-19 related immunization disruptions in Rajasthan, India: A retrospective observational study.

INTRODUCTION: Governments around the world suspended immunization outreach to control COVID-19 spread. Many have since resumed services with an emphasis on catch-up vaccinations. This paper evaluated immunization disruptions during India's March-May 2020 lockdown and the extent to which subsequent catch-up efforts reversed them in Rajasthan, India. METHODS: In this retrospective observational study, we conducted phone surveys to collect immunization details for 2,144 children that turned one year old between January and October 2020. We used logistic regressions to compare differences in immunization timeliness and completed first-year immunization status among children that were due immunizations just before (unexposed), during (heavily exposed), and after (post-exposure) the lockdown. RESULTS: Relative to unexposed children, heavily exposed children were significantly less likely to be immunized at or before 9 months (OR 0.550; 95% CI 0.367-0.824; p = 0.004), but more likely to be immunized at 10-12 months (OR 1.761; 95% CI 1.196-2.591; p = 0.004). They were also less likely to have completed their key first-year immunizations (OR 0.624; 95% CI 0.478-0.816; p = 0.001) by the time of survey. In contrast, post-exposure children showed no difference in timeliness or completed first-year immunizations relative to unexposed children, despite their younger age. First-year immunization coverage among heavily exposed children decreased by 6.9 pp to 10.4 pp (9.7% to 14.0%). Declines in immunization coverage were larger among children in households that were poorer, less educated, lower caste, and residing in COVID red zones, although subgroup comparisons were not statistically significant. CONCLUSION: Disruptions to immunization services resulted in children missing immunization during the lockdown, but catch-up efforts after it was eased ensured many children were reached at later ages. Nevertheless, catch-up was incomplete and children due their immunizations during the lockdown remained less likely to be fully immunized 4-5 months after it lifted, even as younger cohorts due immunizations in June or later returned to pre-lockdown schedules.

COVID-19 mortality effects of underlying health conditions in India: a modelling study.

OBJECTIVE: To model how known COVID-19 comorbidities affect mortality rates and the age distribution of mortality in a large lower-middle-income country (India), and to identify which health conditions drive differences with high-income countries. DESIGN: Modelling study. SETTING: England and India. PARTICIPANTS: Individual data were obtained from the fourth round of the District Level Household Survey and Annual Health Survey in India, and aggregate data were obtained from the Health Survey for England and the Global Burden of Disease, Risk Factors and Injuries Studies. MAIN OUTCOME MEASURES: The primary outcome was the modelled age-specific mortality in each country due to each COVID-19 mortality risk factor (diabetes, hypertension, obesity and respiratory illness, among others). The change in overall mortality and in the share of deaths under age 60 from the combination of risk factors was estimated in each country. RESULTS: Relative to England, Indians have higher rates of diabetes (10.6% vs 8.5%) and chronic respiratory disease (4.8% vs 2.5%), and lower rates of obesity (4.4% vs 27.9%), chronic heart disease (4.4% vs 5.9%) and cancer (0.3% vs 2.8%). Population COVID-19 mortality in India, relative to England, is most increased by uncontrolled diabetes (+5.67%) and chronic respiratory disease (+1.88%), and most reduced by obesity (-5.47%), cancer (-3.65%) and chronic heart disease (-1.20%). Comorbidities were associated with a 6.26% lower risk of mortality in India compared with England. Demographics and population health explain a third of the difference in share of deaths under age 60 between the two countries. CONCLUSIONS: Known COVID-19 health risk factors are not expected to have a large effect on mortality or its age distribution in India relative to England. The high share of COVID-19 deaths from people under age 60 in low- and middle-income countries (LMICs) remains unexplained. Understanding the mortality risk associated with health conditions prevalent in LMICs, such as malnutrition and HIV/AIDS, is essential for understanding differential mortality.

Comprehensive review of guidelines to practice prosthodontic and implant procedures during COVID-19 pandemic.

OBJECTIVES: To present a comprehensive review of current literature available on Corona virus disease and dentistry, modifications required in dental and laboratory settings; and recommended disinfection protocols in current scenario. Special emphasis has been given to discuss guidelines for handling different prosthodontic procedures and implications of this pandemic on prosthodontic practice, education and research. MATERIALS AND METHODS: Relevant literature pertaining to COVID-19 and dentistry was scrutinized on electronic search engines including PubMed, EMBASE and Cochrane. Guidelines given by various organizations, institutions, national and international regulatory bodies and Indian Prosthodontic Society were also consulted to gather information pertaining to the objectives of our review. RESULTS: and observations: A total of 160 articles including cross-sectional studies, in vitro study, narrative reviews, letters to the editor and opinions were found to be relevant in accordance with our search strategy. Documented literature revealed that Covid-19 pandemic has culminated in serious clinical, financial and psychological implications in the field of dentistry. Certain steps such as adoption of teledentistry, judicious use of protective equipment, use of rubber dams, pre-procedural rinses have been suggested unanimously. However, there is a dearth of evidence-based recommendations in literature. Data regarding consequences of delaying prosthodontic procedures and patients' perspectives is also sparse. CONCLUSION: The COVID-19 necessitates the need to adopt a balanced approach while treating patients and safeguarding the dental professionals at the same time. Risk-benefit ratio has to be assessed along with stringent following of guidelines and disinfection protocols to combat this unprecedented situation.

The MpkA MAP kinase module regulates cell wall integrity signaling and pyomelanin formation in Aspergillus fumigatus.

Aspergillus fumigatus is the most important air-borne fungal pathogen, causing severe infections in immunocompromised patients. Mitogen-activated protein kinase (MAPK) signaling pathways are involved in the regulation of various cellular responses to environmental changes in eukaryotes. Genome Blast analysis revealed that the central core of the cell wall integrity signaling pathway in A. fumigatus is composed of three protein kinases designated Bck1, Mkk2 and MpkA. This pathway is of particular interest because it represents a possible target for new antifungal drugs. Deletion of these genes resulted in severe sensitivity of the mutants against cell wall-disturbing compounds and drastic alterations of the fungal morphology. Western blot analysis demonstrated that Bck1 and Mkk2 directly activate MpkA during vegetative growth and under cell wall stress conditions further confirming that Bck1, Mkk2 and MpkA form a MAP kinase module. Interestingly, this MAP kinase module affects the formation of pyomelanin derived from tyrosine degradation.

The mitogen-activated protein kinase MpkA of Aspergillus fumigatus regulates cell wall signaling and oxidative stress response.

Mitogen-activated protein kinase (MAPK) signaling pathways are involved in the regulation of various cellular responses in eukaryotes. In fungal pathogens they are of special interest because of their possible contribution to pathogenicity. Bioinformatic analysis of the genome of the most prevalent airborne human pathogenic fungus Aspergillus fumigatus, revealed the presence of four distinct MAPK-encoding genes. Here, we present the detailed functional analysis of one of these MAPKs, MpkA. Comparative analysis revealed similarities of MpkA with MAPKs involved in cell wall integrity signaling of other fungi. Accordingly, the analysis of mpkA deletion mutants revealed severe sensitivity of the mutants against cell wall active compounds, drastical alterations of the fungal morphology and increased resistance against oxidative stress. The expression of mpkA was induced by cell wall damaging conditions. Despite its involvement in cell wall signaling no influence on virulence of the deletion of mpkA was observed in a murine infection model.