From Over-Tourism to Under-Tourism via COVID-19: Lessons for Sustainable Tourism Management.

With various strains of the novel coronavirus emerging during the last few years, there is a need to reinvent and manage the tourism industry by engaging various stakeholders. Industry and policymakers need to observe the shift and curate tourism-related products and offerings accordingly. In light of the increasing demand for innovations and future directions in the post-COVID-19 period, this article conducts a bibliometric analysis for sustainable tourism studies spanning the years 1990-2021. This paper presents an integrative review of tourism, environment and sustainable tourism to reveal geographical, contextual, and methodological directions for future research. The comprehensive analysis includes contributions on topics and methods, country collaborations, and thematic analysis. The findings are consistent with the Sustainable Development Goals of sustainable production and consumption (SDG-12), with a particular emphasis on sustainable tourism to promote local culture and create jobs (SDG-12.b) and on sustainable growth (SDG-13). The study's findings can be used to inform future policies and directions; for example, the findings indicate that the hospitality industry is facing challenges that necessitate new regulations to address its socioeconomic and environmental impacts.

Carbon conundrums: Geopolitical clashes and market mayhem in the race for sustainability.

This research presents an in-depth investigation into the dynamic correlation between geopolitical conflicts and carbon markets utilizing the Time-Varying Parameter Vector Autoregression (TVP-VAR) technique. The analysis focuses on the interconnectedness between the Geopolitical Risk Index Daily (GPRD) and vital carbon pricing instruments, specifically the Intercontinental Exchange Endex European Union Allowance (ECEFDC), KraneShares California Carbon Allowance Strat ETF (KCCAK), Shanghai Environment and Energy Exchange China Emission Allowances Online Transactions (SAXCEA), and S&P Global Ex-Japan LargeMidCap Carbon Efficient Index (SPGJ). The daily fluctuations were traced from May 2021 to July 2023. The analysis is divided into short- and long-term connectedness, with particular emphasis on the impact of the Russia-Ukraine conflict on the GPRD's spillover on carbon markets. The short-term connectedness (1-5 days) between GPRD and ECEFDC shows variability, fluctuating between 10% and 40%. Conversely, long-term connectedness exhibited a significant increase during the conflict, peaking at approximately 34% by mid-2022. The analysis of the Total Dynamic Connectedness (TCI) between the GPRD and the KCCAK indicates comparable magnitudes, although with minor initial discrepancies. The short-term connectedness of GPRD and KCCAK decreases from its peak of approximately 10% to approximately 1%. Conversely, long-term connectedness varies between approximately 32% and 2% from May 2022 onwards. The long-term connectedness between GPRD and SAXCEA revealed variable patterns, peaking at around 18% at the beginning of the sample period and rapidly reducing to around 1% within two months. The analysis of the connectedness between GPRD and the SPG) identifies intense fluctuations in both TCI and long-term connectedness. After an initial increase and decrease, these patterns rebound and experience another increase. This research provides significant insights into the complex dynamics of geopolitical conflicts and carbon markets, particularly the impact of the Russia-Ukraine conflict on carbon market behavior.

Work from home practices as corporate strategy- an integrative review.

The Covid 19 pandemic led to major changes at the individual, organisational and institutional levels of policy, productive functions, and organising. During Covid 19 morbidity, public institutions enforced social isolation, mandatory self-isolation, quarantines, and administrative regulatory lockdowns, which led to a movement away from the physical, material world and into an all-consuming digital universe. With growing interest in work-from-home (WFH) opportunities, this article provides an integrative review of 107 papers. It comprises the bibliometric analysis and manual review of the articles, on the basis of which we present an elaborative discussion and agenda for future research. According to the analysis, WFH looks a tad of a double-edged sword in that it may have major but unintended repercussions for institutions, and organizations as well as hidden, positive as well as negative consequences for individuals/employees. One of the significant insight from our analysis was the absence of HR function's strategic or operational input or oversight during corporate WFH strategies. We suggest several theoretical frameworks for further developing, theorizing, and empirically testing various aspects of WFH. Further, we recognise that WFH is becoming increasingly visible as a result of the pandemic scenario and significant technical advancements, which must be reflected in the research. Finally, because WFH represents a significant disruption in how organizations produce work and manage it, we propose employee and managerial consequences as future research agendas.

Exposure to High Dosage of Gold Nanoparticles Accelerates Growth Rate by Modulating Ribosomal Protein Expression.

Gold nanoparticles (AuNPs) have been utilized in various biomedical applications including diagnostics and drug delivery. However, the cellular and metabolic responses of cells to these particles remain poorly characterized. In this study, we used bacteria (Escherichia coli and Bacillus subtilis) and a fungus (Saccharomyces cerevisiae) as model organisms to investigate the cellular and metabolic effects of exposure to different concentrations of citrate-capped spherical AuNPs with diameters of 5 and 10 nm. In different growth media, the synthesized AuNPs displayed stability and microorganisms exhibited uniform levels of uptake. Exposure to a high concentration of AuNPs (1012 particles) resulted in a reduced cell division time and a 2-fold increase in cell density in both bacteria and fungus. The exposed cells exhibited a decrease in average cell size and an increase in the expression of FtsZ protein (cell division marker), further supporting an accelerated growth rate. Notably, exposure to such a high concentration of AuNPs did not induce DNA damage, envelope stress, or a general stress response in bacteria. Differential whole proteome analysis revealed modulation of ribosomal protein expression upon exposure to AuNPs in both E. coli and S. cerevisiae. Interestingly, the accelerated growth observed upon exposure to AuNPs was sensitive to sub-minimum inhibitory concentration (sub-MIC) concentration of drugs that specifically target ribosome assembly and recycling. Based upon these findings, we hypothesize that exposure to high concentrations of AuNPs induces stress on the translation machinery. This leads to an increase in the protein synthesis rate by modulating ribosome assembly, which results in the rapid proliferation of cells.

What do we learn from Nexus between trade diversification and structural change: informing the future about climate action and Sustainability.

Economic complexity is considered key a driver of social change, structural change, and economic development. Economic complexity is mostly used to capture issues apropos product diversification of exports, trade, technological innovation, human knowledge, and skills. The current study has conducted a detailed bibliometric review of economic complexity, export quality, and trade diversification. In doing so, the authors used the literature up to 2021 to unveil economic complexity's contextual information that witnessed structural change, social change, and trade indicators. The current study is the first integrative review to report the theoretical contribution, future research agendas, and thematic analysis of economic complexity, export quality, and export diversification. Our study, on the subject of economic complexity, export diversification, and import diversification in the period from 1966 to 2021, was carried out by systematically scanning 386 documents, and it is one of the pioneering studies in this field. In addition, economic diversity, development, and economic complexity; export diversification, import diversification, trade openness, and economic growth; energy, environmental Kuznets curve, and economic complexity; and sustainability and economic diversification are the four main research topics of the study. The findings are discussed apropos of economic complexity and exports, methodological aspects of economic complexity, and environmental issues nexus with economic complexity. The current study reports novel findings toward a path for achieving SDG-9 (industry and innovation) and SDG-13 (climate action). The biometric review enables researchers and policymakers to understand export quality, economic complexity, and the trade nexus and report future research directions for achieving sustainable growth in industries and innovation.

Live Cells Imaging and Comparative Phosphoproteomics Uncover Proteins from the Mechanobiome in Entamoeba histolytica.

Entamoeba histolytica is a protozoan parasite and the causative agent of amoebiasis in humans. This amoeba invades human tissues by taking advantage of its actin-rich cytoskeleton to move, enter the tissue matrix, kill and phagocyte the human cells. During tissue invasion, E. histolytica moves from the intestinal lumen across the mucus layer and enters the epithelial parenchyma. Faced with the chemical and physical constraints of these diverse environments, E. histolytica has developed sophisticated systems to integrate internal and external signals and to coordinate cell shape changes and motility. Cell signalling circuits are driven by interactions between the parasite and extracellular matrix, combined with rapid responses from the mechanobiome in which protein phosphorylation plays an important role. To understand the role of phosphorylation events and related signalling mechanisms, we targeted phosphatidylinositol 3-kinases followed by live cell imaging and phosphoproteomics. The results highlight 1150 proteins, out of the 7966 proteins within the amoebic proteome, as members of the phosphoproteome, including signalling and structural molecules involved in cytoskeletal activities. Inhibition of phosphatidylinositol 3-kinases alters phosphorylation in important members of these categories; a finding that correlates with changes in amoeba motility and morphology, as well as a decrease in actin-rich adhesive structures.

Treatment effects and lip profile changes following premolars extraction treatment vs fixed functional treatment in Class II division 1 malocclusion: A randomized controlled clinical trial.

OBJECTIVE: The objective of this two-arm parallel randomized controlled trial was to evaluate the treatment effects and lip profile changes in skeletal Class II patients subjected to premolars extraction treatment versus fixed functional treatment. METHODS: Forty six subjects fulfilling inclusion criteria were randomly distributed into Group PE (mean age 13.03±1.78 years) and Group FF (mean age 12.80±1.67 years) (n=23 each). Group PE was managed by therapeutic extraction of maxillary first premolars and mandibular second premolars, followed by mini-implant-supported space closure; and Group FF, by fixed functional appliance therapy. Skeletal, dental, and soft-tissue changes were analyzed using pre and post-treatment lateral cephalograms. Data obtained from this open label study was subjected to blind statistical analysis. RESULTS: Extraction treatment resulted in greater increase of nasolabial angle (NLA: 3.1 [95% CI 2.08, 4.19], p<0.001), significant improvement of upper lip (UL-E line: -2.91 [95% CI -3.54, -2.28], p<0.001, UL-S line: -2.50 [95% CI -2.76, -2.24], p<0.001, UL-SnPog': -2.32 [95% CI -2.90, -1.74], p<0.01) and lower lip position (LL-E line: -0.68 [95% CI -1.36, 0.00], p<0.01, LL-S line: -0.55 [95% CI -1.11, 0.02], p<0.01, and LL-SnPog': -0.64 [95% CI -1.20, -0.07], p<0.01), lip thickness (UL thickness: 2.27 [95% CI 1.79, 2.75], p<0.001; LL thickness: 0.41 [95% CI -0.16, 0.97], p<0.01), upper lip strain (UL strain: -2.68 [95% CI -3.32, -2.04], p<0.001) and soft tissue profile (N'-Sn-Pog': 2.68 [95% CI 1.87, 3.50], p<0.01). No significant difference was observed between the groups regarding skeletal changes in the maxilla and mandible, growth pattern, overjet, overbite, interincisal angle and soft tissue chin position (p>0.05). Premolar extraction treatment demonstrated significant intrusion-retraction of maxillary incisors, better maintenance of maxillary incisor inclination, and significant mandibular molar protraction; whereas functional treatment resulted in retrusive and intrusive effect on maxillary molars, marked proclination of mandibular anterior teeth, and significant extrusion of mandibular molars. Both treatment modalities had similar treatment duration. Implant failure was seen in 7.9% of cases, whereas failure of fixed functional appliance was observed in 9.09% of cases. CONCLUSIONS: Premolar extraction therapy is a better treatment modality, compared to fixed functional appliance therapy for Class II patients with moderate skeletal discrepancy, increased overjet, protruded maxillary incisors and protruded lips, as it produces better dentoalveolar response and permits greater improvement of the soft tissue profile and lip relationship.

Elevated inorganic carbon and salinity enhances photosynthesis and ATP synthesis in picoalga Picocystis salinarum as revealed by label free quantitative proteomics.

Saline soda lakes are of immense ecological value as they niche some of the most exclusive haloalkaliphilic communities dominated by bacterial and archaeal domains, with few eukaryotic algal representatives. A handful reports describe Picocystis as a key primary producer with great production rates in extremely saline alkaline habitats. An extremely haloalkaliphilic picoalgal strain, Picocystis salinarum SLJS6 isolated from hypersaline soda lake Sambhar, Rajasthan, India, grew robustly in an enriched soda lake medium containing mainly Na2CO3, 50 g/l; NaHCO3, 50 g/l, NaCl, 50 g/l (salinity ≈150‰) at pH 10. To elucidate the molecular basis of such adaptation to high inorganic carbon and NaCl concentrations, a high-throughput label-free quantitation based quantitative proteomics approach was applied. Out of the total 383 proteins identified in treated samples, 225 were differentially abundant proteins (DAPs), of which 150 were statistically significant (p < 0.05) including 70 upregulated and 64 downregulated proteins after 3 days of growth in highly saline-alkaline medium. Most DAPs were involved in photosynthesis, oxidative phosphorylation, glucose metabolism and ribosomal structural components envisaging that photosynthesis and ATP synthesis were central to the salinity-alkalinity response. Key components of photosynthetic machinery like photosystem reaction centres, adenosine triphosphate (ATP) synthase ATP, Rubisco, Fructose-1,6-bisphosphatase, Fructose-bisphosphate aldolase were highly upregulated. Enzymes peptidylprolyl isomerases (PPIase), important for correct protein folding showed remarkable marked-up regulation along with other chaperon proteins indicating their role in osmotic adaptation. Enhanced photosynthetic activity exhibited by P. salinarum in highly saline-alkaline condition is noteworthy as photosynthesis is suppressed under hyperosmotic conditions in most photosynthetic organisms. The study provided the first insights into the proteome of extremophilic alga P. salinarum exhibiting extraordinary osmotic adaptation and proliferation in polyextreme conditions prevailing in saline sodic ecosystems, potentially unraveling the basis of resilience in this not so known organism and paves the way for a promising future candidate for biotechnological applications and model organism for deciphering the molecular mechanisms of osmotic adaptation. The mass spectrometry proteomics data is available at the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD037170.

Amylo-AFFECT-QOL, a self-reported questionnaire to assess health-related quality of life and to determine the prognosis in cardiac amyloidosis.

Background and aims: Self-reported questionnaires are useful for estimating the health-related quality of life (HR-QoL), impact of interventions, and prognosis. To our knowledge, no HR-QoL questionnaire has been developed for cardiac amyloidosis (CA). This study aimed to validate Amylo-AFFECT-QOL questionnaire to assess HR-QoL and its prognostic value in CA. Methods: A self-reported questionnaire, "Amylo-AFFECT" had been designed and validated for CA symptoms evaluation and screening by physicians. It was adapted here to assess HR-QoL (Amylo-AFFECT-QOL) and its prognostic value in CA. To validate the theoretical model, internal consistency and convergent validity were assessed, particularly correlations between Amylo-AFFECT-QOL and the HR-QoL Minnesota Living Heart Failure (MLHF) questionnaire. Results: Amylo-AFFECT-QOL was completed by 515 patients, 425 of whom (82.5%) had CA. Wild-type and hereditary transthyretin amyloidosis (ATTRwt and ATTRv) and immunoglobulin light-chain amyloidosis (AL) were diagnosed in 47.8, 14.7, and 18.8% of cases, respectively. The best HR-QoL evaluation was obtained with five dimensions: "Heart failure," "Vascular dysautonomia," "Neuropathy," "Ear, gastrointestinal, and urinary dysautonomia," and "Skin or mucosal involvement." The global Amylo-AFFECT-QOL and MLHF scores showed significant positive correlations (rs = 0.72, p < 0.05). Patients with a final diagnosis of CA had a global Amylo-AFFECT-QOL score significantly higher than the control group composed by patients with other diagnoses (22.2 ± 13.6 vs. 16.2 ± 13.8, respectively, p-value < 0.01). According to the Amylo-AFFECT-QOL global results, ATTRv patients' QoL was more affected than AL patients' QoL or ATTRwt patients' QoL. Patients with a higher HR-QoL score had a greater risk of death or heart transplant after 1 year of follow-up (log-rank < 0.01). Conclusion: Amylo-AFFECT-QOL demonstrates good psychometric properties and is useful for quantifying HR-QoL and estimating CA prognosis. Its use may help to improve overall management of patients with CA.

Transcription coupled DNA repair protein UVSSA binds to DNA and RNA: Mapping of nucleic acid interaction sites on human UVSSA.

Transcription-coupled repair (TCR) is a dedicated pathway for the preferential repair of bulky transcription-blocking DNA lesions. These lesions stall the elongating RNA-polymerase II (RNAPII) triggering the recruitment of TCR proteins at the damaged site. UV-stimulated scaffold protein A (UVSSA) is a recently identified cofactor which is involved in stabilization of the TCR complex, recruitment of DNA-repair machinery and removal/restoration of RNAPII from the lesion site. Mutations in UVSSA render the cells TCR-deficient and have been linked to UV-sensitive syndrome. Human UVSSA is a 709-residue long protein with two short conserved domains; an N-terminal (residues 1-150) and a C-terminal (residues 495-605) domain, while the rest of the protein is predicted to be intrinsically disordered. The protein is well conserved in eukaryotes, however; none of its homologs have been characterized yet. Here, we have purified the recombinant human UVSSA and have characterized it using bioinformatics, biophysical and biochemical techniques. Using EMSA, SPR and fluorescence-based methods, we have shown that human UVSSA interacts with DNA and RNA. Furthermore, we have mapped the nucleic acid binding regions using several recombinant protein fragments containing either the N-terminal or the C-terminal domains. Our data indicate that UVSSA possesses at least two nucleic acid binding regions; the N-terminal domain and a C-terminal tail region (residues 606-662). These regions, far apart in sequence space, are predicted to be in close proximity in structure-space suggesting a coherent interaction with target DNA/RNA. The study may provide functional clues about the novel family of UVSSA proteins.

Natural course and determinants of short-term kidney function decline in hereditary transthyretin amyloidosis: a French observational study.

Data regarding renal involvement in patients with hereditary transthyretin (ATTRv) amyloidosis are scarce and the natural course of chronic kidney disease (CKD) in this population remains unclear. This observational study, including adult patients diagnosed with ATTRv amyloidosis at the French Reference Centre for Cardiac Amyloidosis, investigated renal function outcome and its determinants. Multivariable logistic regression models identified factors associated with CKD at baseline. Determinants of the change in estimated glomerular filtration rate (eGFR) over 24 months of follow-up were assessed with a multivariable linear mixed-effects model. In total, 232 patients (78 women [34%], mean age: 64 years) with ATTRv amyloidosis were classified on the basis of their TTR variants: ATTRV122I (37%), ATTRV30M (29%), and other variants (34%). Median baseline eGFR was 78 ml/min/1.73 m2. Seventy-two patients (31%) had an eGFR below 60 ml/min/1.73m2 and 27/137 patients (20%) had significant proteinuria (urine protein/creatinine ratio ≥30 mg/mmol). Renal biopsy, performed in four cases, found typical Congo red-positive and TTR-labelled amyloid deposits in all cases. Older age (OR 1.07, p < .001) and a prior history of hypertension (OR 2.09, p = .04) were associated with a higher prevalence of CKD at baseline, whereas higher left ventricular global longitudinal strain (LVGLS) (OR 0.83, p < .001) was associated with a lower prevalence. The estimated change in eGFR was -7.12 [-9.61, -4.63] and -8.21 [-10.81, -5.60] ml/min/1.73 m2 after 12 and 24 months of follow-up, respectively. eGFR decline was independently associated with older age ((67-74], coefficient= -14.35 mL/min/1.73 m2, p < .01, >74, coefficient = -22.93 mL/min/1.73 m2, p < .001, versus <56), ATTRV122I (coefficient = -17.17 mL/min/1.73m2, p < .01, versus ATTRV30M) and LVGLS (coefficient = 1.22, p < .01). These data suggest that CKD is a common finding in patients with ATTRv amyloidosis, and that eGFR decline is rapid during the first year of evaluation. Older age, lower LVGLS and ATTRV122I were associated with a worse renal outcome. Further studies are now needed to evaluate effects of new targeted therapies on long term renal function.

Treatment effects and lip profile changes following premolars extraction treatment vs fixed functional treatment in Class II division 1 malocclusion: A randomized controlled clinical trial

ABSTRACT Objective: The objective of this two-arm parallel randomized controlled trial was to evaluate the treatment effects and lip profile changes in skeletal Class II patients subjected to premolars extraction treatment versus fixed functional treatment. Methods: Forty six subjects fulfilling inclusion criteria were randomly distributed into Group PE (mean age 13.03±1.78 years) and Group FF (mean age 12.80±1.67 years) (n=23 each). Group PE was managed by therapeutic extraction of maxillary first premolars and mandibular second premolars, followed by mini-implant-supported space closure; and Group FF, by fixed functional appliance therapy. Skeletal, dental, and soft-tissue changes were analyzed using pre and post-treatment lateral cephalograms. Data obtained from this open label study was subjected to blind statistical analysis. Results: Extraction treatment resulted in greater increase of nasolabial angle (NLA: 3.1 [95% CI 2.08, 4.19], p<0.001), significant improvement of upper lip (UL-E line: -2.91 [95% CI -3.54, -2.28], p<0.001, UL-S line: -2.50 [95% CI -2.76, -2.24], p<0.001, UL-SnPog': -2.32 [95% CI -2.90, -1.74], p<0.01) and lower lip position (LL-E line: -0.68 [95% CI -1.36, 0.00], p<0.01, LL-S line: -0.55 [95% CI -1.11, 0.02], p<0.01, and LL-SnPog': -0.64 [95% CI -1.20, -0.07], p<0.01), lip thickness (UL thickness: 2.27 [95% CI 1.79, 2.75], p<0.001; LL thickness: 0.41 [95% CI -0.16, 0.97], p<0.01), upper lip strain (UL strain: -2.68 [95% CI -3.32, -2.04], p<0.001) and soft tissue profile (N'-Sn-Pog': 2.68 [95% CI 1.87, 3.50], p<0.01). No significant difference was observed between the groups regarding skeletal changes in the maxilla and mandible, growth pattern, overjet, overbite, interincisal angle and soft tissue chin position (p>0.05). Premolar extraction treatment demonstrated significant intrusion-retraction of maxillary incisors, better maintenance of maxillary incisor inclination, and significant mandibular molar protraction; whereas functional treatment resulted in retrusive and intrusive effect on maxillary molars, marked proclination of mandibular anterior teeth, and significant extrusion of mandibular molars. Both treatment modalities had similar treatment duration. Implant failure was seen in 7.9% of cases, whereas failure of fixed functional appliance was observed in 9.09% of cases. Conclusions: Premolar extraction therapy is a better treatment modality, compared to fixed functional appliance therapy for Class II patients with moderate skeletal discrepancy, increased overjet, protruded maxillary incisors and protruded lips, as it produces better dentoalveolar response and permits greater improvement of the soft tissue profile and lip relationship.

RESUMO Objetivo: O objetivo desse estudo randomizado controlado paralelo de dois braços foi avaliar os efeitos do tratamento e as mudanças no perfil labial em pacientes esqueléticos Classe II submetidos a tratamento com extração de pré-molares (EP) versus tratamento funcional fixo (FF). Métodos: Quarenta e seis indivíduos que preencheram os critérios de inclusão foram distribuídos aleatoriamente em Grupo EP (idade média 13,03±1,78 anos) e Grupo FF (idade média 12,80±1,67 anos) (n=23 cada). O grupo EP foi tratado com extração dos primeiros pré-molares superiores e segundos pré-molares inferiores, seguida de fechamento do espaço com ancoragem em mini-implantes; e o Grupo FF, com tratamento usando aparelhos funcionais fixos. As alterações esqueléticas, dentárias e de tecidos moles foram analisadas usando cefalogramas laterais pré e pós-tratamento. Os dados obtidos desse estudo aberto foram submetidos a análise estatística cega. Resultados: O tratamento com extrações resultou em maior aumento do ângulo nasolabial (ANL: 3,1 [IC 95% 2,08, 4,19], p<0,001), melhora significativa do lábio superior (Ls-Linha E: -2,91 [IC 95% -3,54, -2,28], p<0,001, Ls-Linha S: -2,50 [IC 95% -2,76, -2,24], p<0,001, Ls-SnPog': -2,32 [IC 95% -2,90, -1,74], p<0,01) e posição do lábio inferior (Li-Linha E: -0,68 [IC 95% -1,36, 0,00], p<0,01, Li-Linha S: -0,55 [IC 95% -1,11, 0,02], p<0,01, e Li-SnPog': -0,64 [IC 95% -1,20, -0,07], p<0,01), espessura dos lábios (espessura Ls: 2,27 [IC 95% 1,79, 2,75], p<0,001; espessura Li: 0,41 [IC 95% -0,16, 0,97], p<0,01), tensão do lábio superior (tensão Ls: -2,68 [IC 95% -3,32, -2,04], p<0,001) e perfil de tecidos moles (N'-Sn-Pog': 2,68 [IC 95% 1,87, 3,50], p<0,01). Nenhuma diferença significativa foi observada entre os grupos quanto às alterações esqueléticas na maxila e mandíbula, padrão de crescimento, sobressaliência, sobremordida, ângulo interincisal e posição dos tecidos moles do mento (p>0,05). O tratamento com extração de pré-molares demonstrou significativa intrusão-retração dos incisivos superiores, melhor manutenção da inclinação dos incisivos superiores e protração significativa dos molares inferiores; enquanto o tratamento funcional resultou em efeito retrusivo e intrusivo nos molares superiores, proclinação acentuada dos dentes anteriores inferiores e extrusão significativa dos molares inferiores. Ambas as modalidades de tratamento tiveram duração de tratamento semelhante. A falha do mini-implante foi observada em 7,9% dos casos, enquanto a falha do aparelho funcional fixo foi observada em 9,09% dos casos. Conclusões: O tratamento com extração de pré-molares é uma modalidade de tratamento melhor do que os aparelhos funcionais fixos para pacientes Classe II com discrepância esquelética moderada, sobressaliência aumentada, incisivos superiores protruídos e lábios protruídos, pois produz melhor resposta dentoalveolar e permite maior melhora do perfil dos tecidos moles e relacionamento labial.

Multi-omics analysis to characterize molecular adaptation of Entamoeba histolytica during serum stress.

Entamoeba histolytica is responsible for dysentery and extraintestinal disease in humans. To establish successful infection, it must generate adaptive response against stress due to host defense mechanisms. We have developed a robust proteomics workflow by combining miniaturized sample preparation, low flow-rate chromatography, and ultra-high sensitivity mass spectrometry, achieving increased proteome coverage, and further integrated proteomics and RNA-seq data to decipher regulation at translational and transcriptional levels. Label-free quantitative proteomics led to identification of 2344 proteins, an improvement over the maximum number identified in E. histolytica proteomic studies. In serum-starved cells, 127 proteins were differentially abundant and were associated with functions including antioxidant activity, cytoskeleton, translation, catalysis, and transport. The virulence factor, Gal/GalNAc-inhibitable lectin subunits, was significantly altered. Integration of transcriptomic and proteomic data revealed that only 30% genes were coordinately regulated at both transcriptional and translational levels. Some highly expressed transcripts did not change in protein abundance. Conversely, genes with no transcriptional change showed enhanced protein abundance, indicating post-transcriptional regulation. This multi-omics approach enables more refined gene expression analysis to understand the adaptive response of E. histolytica during growth stress.

PROTACs: A Hope for Breast Cancer Patients?

BACKGROUND: Breast Cancer (BC) is the most widely occurring disease in women. A massive number of women are diagnosed with breast cancer, and many lose their lives every year. Cancer is the leading cause of death worldwide, posing a formidable challenge to the current medication difficulties. OBJECTIVES: The main objective of this study is to examine and explore novel therapy (PROTAC) and its effectiveness against breast cancer. METHODS: The literature search was conducted across Medline, Cochrane, ScienceDirect, Wiley Online, Google Scholar, PubMed, and Bentham Sciences from 2001 to 2020. The articles collected were screened, segregated, and selected papers were included for writing the review article. RESULTS AND CONCLUSION: A novel innovation emerged around two decades ago that has great potential to overcome the limitations and provide future direction for the treatment of many diseases, which has presently not many therapeutic options available and are regarded as incurable with traditional techniques. That innovation is called PROTAC (Proteolysis Targeting Chimera), which can efficaciously ubiquitinate and debase cancer, encouraging proteins through noncovalent interaction. PROTACs constituted of two active regions isolated by a linker are equipped for eliminating explicit undesirable protein. It is empowering greater sensitivity to "drugresistant targets" and a more prominent opportunity to influence non-enzymatic function. PROTACs have been demonstrated to show better target selectivity contrasted with traditional small-molecule inhibitors. So far, the most investigation into PROTACs mainly concentrated on cancer treatment applications, including breast cancer. The treatment of different ailments may benefit the patients from this blossoming innovation.

Molecular basis for reduced cleavage activity and drug resistance in D30N HIV-1 protease.

Nelfinavir is one of the FDA-approved HIV-1 protease inhibitors and a part of highly active anti-retroviral therapy (HAART) for the treatment of HIV-AIDS. Nelfinavir was the first HIV-1 protease inhibitor to be approved as a paediatric formulation. The application of HAART had resulted in significant improvement in the lives of AIDS patients. However, the emergence of drug resistance in HIV-1 protease has limited the use of many of these drugs including nelfinavir. A unique mutation observed frequently in patients treated with nelfinavir is D30N as it is selected exclusively by nelfinavir. The D30N mutation imparts very high resistance to nelfinavir but unlike other primary mutations does not give cross-resistance to the majority of other drugs. D30N mutation also significantly reduces cleavage activity of HIV-1 protease and affects viral fitness. Here, we have determined crystal structures of D30N HIV-1 protease in unliganded form and in complex with nelfinavir. These structures provide the rationale for reduced cleavage activity and the molecular basis of drug resistance induced by D30N mutation. The loss of coulombic interaction part of a crucial hydrogen bond between the drug and the protease is likely to play a major role in reduced affinity and resistance towards nelfinavir. The decreased catalytic activity of D30N HIV-1 protease due to altered interaction with the substrates and reduced stability of folding core may be the reason for the reduced replicative capacity of the virus harboring mutant HIV-1 protease.Communicated by Ramaswamy H. Sarma.

Treatment Effects and Lip Profile Changes Following Surgical Mandibular Advancement Versus Premolar Extractions in Class II Div 1 Malocclusion: A Randomized Controlled Trial.

ABSTRACT: No randomized controlled trial has compared the treatment outcome between surgical mandibular advancement and premolar extractions in class II malocclusion. This 2-arm parallel randomized controlled trial evaluated the treatment effects and lip profile changes in skeletal class II adult patients subjected to bilateral sagittal split ramus osteotomy for mandibular advancement and those treated with premolar extractions. Seventy skeletal class II patients were accessed and forty-six subjects who fulfilled inclusion criteria were distributed randomly into Group CG (patients: 23, mean age: 21.28 ±â€Š2.69 years) and Group SG (patients: 23, mean age: 21.15 ±â€Š2.64 years). Group CG was subjected to extraction of maxillary first premolars and mandibular second premolars followed by implant supported space closure and Group SG was managed by surgical mandibular advancement. Skeletal, dental, and soft-tissue changes were analyzed. The study was single-blinded (statistical analyzer). Groups were closely matched for baseline parameters. In the present trial there was no loss to follow-up. Though overjet and overbite were optimized in both the groups but significant improvement was seen in surgical cases. Group CG demonstrated statistically significant point "A" remodeling, dentoalveolar changes, and increase in nasolabial angle. Group SG exhibited significant sagittal and vertical skeletal improvement and lip position change. Surgical mandibular advancement was found to be a better treatment modality compared to premolars extraction for managing skeletal class II div 1 malocclusion as it permits greater improvement of the profile and skeletal relationship.

Intrinsic bias at non-canonical, ß-arrestin-coupled seven transmembrane receptors.

G-protein-coupled receptors (GPCRs), also known as seven transmembrane receptors (7TMRs), typically interact with two distinct signal-transducers, i.e., G proteins and ß-arrestins (ßarrs). Interestingly, there are some non-canonical 7TMRs that lack G protein coupling but interact with ßarrs, although an understanding of their transducer coupling preference, downstream signaling, and structural mechanism remains elusive. Here, we characterize two such non-canonical 7TMRs, namely, the decoy D6 receptor (D6R) and the complement C5a receptor subtype 2 (C5aR2), in parallel with their canonical GPCR counterparts. We discover that D6R and C5aR2 efficiently couple to ßarrs, exhibit distinct engagement of GPCR kinases (GRKs), and activate non-canonical downstream signaling pathways. We also observe that ßarrs adopt distinct conformations for D6R and C5aR2, compared to their canonical GPCR counterparts, in response to common natural agonists. Our study establishes D6R and C5aR2 as ßarr-coupled 7TMRs and provides key insights into their regulation and signaling with direct implication for biased agonism.

Screening Evaporative Dry Eyes Severity Using an Infrared Image.

BACKGROUND: Dry eye disease (DED) is a multifactorial and one of the most common problems treated in an ophthalmic outpatient clinic. Due to the variability in presentation, diagnosis of DED consists of a combination of subjective and objective clinical tests. The purpose of this study was to assess the effectiveness of a handheld smartphone-based infrared thermal (IRT) camera for screening symptomatic evaporative DED. METHODS: This observational sex-matched control study assessed IRT images of 184 right eyes (46 normal and 138 DED) of 184 participants. Evaporative DED was assessed using noninvasive tear breakup time, fluorescein staining, and the Chinese version of the ocular surface disease index (C-OSDI) questionnaire and categorized into their respective dry eye symptomology group (none, mild, moderate, or severe). The ocular surface temperature (OST) at 8 anatomical regions of interest (ROI) (nasal conjunctiva, nasal limbus, nasal cornea, central cornea, inferior cornea, temporal limbus, temporal cornea, and temporal conjunctiva) were measured and compared using a handheld smartphone-based IRT camera. The effectiveness of these 8 ROIs OST in detecting varying severity of DED was evaluated in terms of correlations with severity of DED and their area under the curve (AUC). RESULTS: OST at the 8 anatomical ROI was significantly higher in DED participants than in the non-DED group (p < 0.05) except for inferior cornea, temporal limbus, and temporal conjunctival regions (>0.05). Analyzing 8 anatomical ROIs revealed that the nasal limbus had the highest Pearson correlation with the severity of DED (0.64, p < 0.001). Additionally, the nasal limbus ROI achieved the highest AUC of 0.79 (CI: 0.73-0.85; p < 0.05), sensitivity, and specificity (0.96 and 0.91) when comparing its ability to discriminated DED vs. non-DED eyes. CONCLUSIONS: Rather than a diagnostic tool, handheld smartphone-based IRT images can be considered as a rapid, noninvasive, and hygienic screening tool in discriminating DED and non-DED and potentially alleviating inconvenience experienced during conventional tests.

COVID-19 and environmental concerns: A rapid review.

COVID-19 has slowed global economic growth and consequently impacted the environment as well. Parallelly, the environment also influences the transmission of this novel coronavirus through various factors. Every nation deals with varied population density and size; air quality and pollutants; the nature of land and water, which significantly impact the transmission of coronavirus. The WHO (Ziaeepour et al., 2008) [1] has recommended rapid reviews to provide timely evidence to the policymakers to respond to the emergency. The present study follows a rapid review along with a brief bibliometric analysis of 328 research papers, which synthesizes the evidence regarding the environmental concerns of COVID-19. The novel contribution of this rapid review is threefold. One, we take stock of the diverse findings as regards the transmission of the novel coronavirus in different types of environments for providing conclusive directions to the ongoing debate regarding the transmission of the virus. Two, our findings provide topical insights as well as methodological guidance for future researchers in the field. Three, we inform the policymakers on the efficacy of environmental measures for controlling the spread of COVID-19.