Emergency room visits (ERVs) among occupational groups associated with ambient conditions in Taiwan.

OBJECTIVE: This population-based study explored emergency room visits (ERVs) from all-causes, circulatory and respiratory diseases among different occupational groups in Taiwan associated with ambient average temperature. METHOD: Daily area-age-sex specific ERVs records were obtained from the Taiwan's Ministry of Health and Welfare from 2009 to 2018. Distributed lag-nonlinear model (DLNM) was used to estimate the exposure-response relationships between daily average temperature and ERVs for all-causes, circulatory and respiratory diseases by occupational groups. Random-effects meta-analysis was used to pool the overall cumulative relative risk (RR) and 95% confidence interval (CI). RESULTS: The exposure-response curves showed ERVs of all-cause and respiratory diseases increased with rising temperature across all occupational groups. These effects were consistently stronger among younger (20-64 years old) and outdoor workers. In contrast, ERVs risk from circulatory diseases increased significantly during cold snaps, with a substantially higher risk for female workers. Interestingly, female workers, regardless of indoor or outdoor work, consistently showed a higher risk of respiratory ERVs during hot weather compared to males. Younger workers (20-64 years old) exhibited a higher risk of ERVs, likely due to job profiles with greater exposure to extreme temperatures. Notably, the highest risk of all-causes ERVs was observed in outdoor male laborers (union members), followed by farmers and private employees, with the lowest risk among indoor workers. Conversely, female indoor workers and female farmers faced the highest risk of respiratory ERVs. Again, female farmers with consistent outdoor exposure had the highest risk of circulatory ERVs during cold conditions. CONCLUSION: Our findings highlighted the complexity of temperature-related health risks associated with different occupational contexts. The population-level insights into vulnerable occupational groups could provide valuable comprehension for policymakers and healthcare practitioners.

Pathogenesis of rheumatoid arthritis and its treatment with anti-inflammatory natural products.

Introduction Rheumatoid arthritis (RA) is a common autoimmune disease across the globe that is chronic and systemic as well. The disease is linked with autoantibodies and is inflammatory, eventually targeting several molecules along with certain modified self-epitopes. The disease majorly affects the joints of an individual. Rheumatoid arthritis is manifested clinically by polyarthritis linked with the dysfunction of the joints. This chiefly affects the synovial joint lining and is linked with progressive dysfunction, premature death, along with socioeconomic implications. The macrophage activation, along with the activation of certain defense cells, results in a response to self-epitopes that helps in providing a better understanding of the disease pathogenesis.  Material and methodology For this review article, papers have been retrieved and reviewed from database including PubMed, Scopus and Web of science. Relevant papers were taken fulfilling the criteria for writing this review article. Results This has resulted in the establishment of several new therapeutic techniques that serve as potential inhibitors of such cells. Researchers have gained an interest in understanding this disease to provide strategies for treatment in the last two decades. This also includes recognition followed by the treatment of the disease at its early stages. Various allopathic treatment approaches often have chronic and toxic teratogenic effects. However, to avoid this issue of toxicity followed by side effects, certain medicinal plants have been used in treating RA.  Conclusion Medicinal plants possess active phytoconstituents that entail antioxidants as well as anti-inflammatory properties, making them a helpful alternative to allopathic drugs that are often linked with highly toxic effects. This review paper entails a thorough discussion of the epidemiology, pathophysiology, diagnosis, and management of RA. The paper will also focus on the use of herbal plants in the treatment of the disease to avoid the side effects that generally occur in allopathic treatment.

Comparative proteomic investigation unravels the pathobiology of Mycobacterium fortuitum biofilm.

Biofilm formation by Mycobacterium fortuitum causes serious threats to human health due to its increased contribution to nosocomial infections. In this study, the first comprehensive global proteome analysis of M. fortuitum was reported under planktonic and biofilm growth states. A label-free Q Exactive Quadrupole-Orbitrap tandem mass spectrometry analysis was performed on the protein lysates. The differentially abundant proteins were functionally characterized and re-annotated using Blast2GO and CELLO2GO. Comparative analysis of the proteins among two growth states provided insights into the phenotypic switch, and fundamental pathways associated with pathobiology of M. fortuitum biofilm, such as lipid biosynthesis and quorum-sensing. Interaction network generated by the STRING database revealed associations between proteins that endure M. fortuitum during biofilm growth state. Hypothetical proteins were also studied to determine their functional alliance with the biofilm phenotype. CARD, VFDB, and PATRIC analysis further showed that the proteins upregulated in M. fortuitum biofilm exhibited antibiotic resistance, pathogenesis, and virulence. Heatmap and correlation analysis provided the biomarkers associated with the planktonic and biofilm growth of M. fortuitum. Proteome data was validated by qPCR analysis. Overall, the study provides insights into previously unexplored biochemical pathways that can be targeted by novel inhibitors, either for shortened treatment duration or for eliminating biofilm of M. fortuitum and related nontuberculous mycobacterial pathogens. KEY POINTS: • Proteomic analyses of M. fortuitum reveals novel biofilm markers. • Acetyl-CoA acetyltransferase acts as the phenotype transition switch. • The study offers drug targets to combat M. fortuitum biofilm infections.

Comparing the Outcomes and Complication Rates of Biologic vs Synthetic Meshes in Implant-Based Breast Reconstruction: A Systematic Review.

OBJECTIVE: This systematic review evaluates all published studies comparing biologic and synthetic meshes in implant-based breast reconstruction (IBBR), to determine which category of mesh produces the most favorable outcomes. SUMMARY BACKGROUND DATA: Breast cancer is the most common cancer in women globally. Implant-based breast reconstruction is currently the most popular method of postmastectomy reconstruction, and recently, the use of surgical mesh in IBBR has become commonplace. Although there is a long-standing belief among surgeons that biologic mesh is superior to synthetic mesh in terms of surgical complications and patient outcomes, few studies exist to support this claim. METHODS: A systematic search of the EMBASE, PubMed, and Cochrane databases was performed in January 2022. Primary literature studies comparing biologic and synthetic meshes within the same experimental framework were included. Study quality and bias were assessed using the validated Methodological Index for Non-Randomized Studies criteria. RESULTS: After duplicate removal, 109 publications were reviewed, with 12 meeting the predetermined inclusion criteria. Outcomes included common surgical complications, histological analysis, interactions with oncologic therapies, quality of life measures, and esthetic outcomes. Across all 12 studies, synthetic meshes were rated as at least equivalent to biologic meshes for every reported outcome. On average, the studies in this review tended to have moderate Methodological Index for Non-Randomized Studies scores. CONCLUSION: This systematic review offers the first comprehensive evaluation of all publications comparing biologic and synthetic meshes in IBBR. The consistent finding that synthetic meshes are at least equivalent to biologic meshes across a range of clinical outcomes offers a compelling argument in favor of prioritizing the use of synthetic meshes in IBBR.

Technical Tips to Reduce Implant Rippling in Staged Pre-pectoral Breast Reconstruction.

INTRODUCTION: Pre-pectoral implant-based breast reconstruction (IBR) is becoming increasingly popular, permitting optimal implant positioning on the chest wall, prevention of animation deformity, and reduced patient discomfort. There are, however, concerns related to increased rates of breast implant rippling in pre-pectoral (versus submuscular) IBR, which can prompt a patient to seek revisionary surgery. The aim of this study is to identify factors that can be implemented to reduce implant rippling in the setting of pre-pectoral IBR. METHODS: A literature review was conducted using the PubMed database to determine the rate of rippling in pre-pectoral IBR. Clinical studies in English were included. Further review was then performed to explore technical strategies associated with reduced rates of rippling in pre-pectoral two-stage breast reconstruction. RESULTS: Implant rippling has been reported with a rate varying from 0 to 53.8% in 25 studies of pre-pectoral IBR (including both direct-to-implant and two-stage IBR). The majority of studies reviewed did not demonstrate a significant association between BMI and rippling, suggesting that other factors, likely technical and device-related, contribute to the manifestation of implant rippling. Hence, we explored whether specific technical modifications could be implemented that would reduce the risk of rippling in patients undergoing pre-pectoral IBR. Specifically, we highlight the need for close attention to expansion protocol and pocket dimension, expander fill medium and implant characteristics, and the rationale behind adjunctive procedures to reduce implant rippling. CONCLUSION: Surgical modifications may reduce the incidence of rippling in pre-pectoral breast reconstruction. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

In Vitro and In Silico Anti-Rheumatic Arthritis Activity of Nyctanthes arbor-tristis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by bone and joint degeneration. Existing anti-inflammatory chemotherapy drugs offer temporary relief but come with undesirable side effects. Herbal medications have shown positive effects on RA symptoms with minimal adverse reactions. In this study, we investigated the potential of Nyctanthes arbor-tristis (NAT) through in vitro and in silico research. Hydroethanolic extracts of harsingar were prepared using the reflux method, containing alkaloids, phenol, saponin, steroids, proteins, tannins, terpenoids, carbohydrates, glycosides, and flavonoids, which exhibited TPC (98.56 ± 0.46 mg GAE/g) and TFC (34.51 ± 0.45 mg CE/g). LC-MS/MS analyzes the active compounds in the extract. NAT exhibited the best scavenging capabilities at 1 mg/mL in anti-oxidant and anti-arthritic activity. Maximum splenocyte proliferation occurred at 250 µg/mL. In vitro cell splenocyte studies revealed the downregulation of TNF-α and the upregulation of IL-10. Additionally, an in silico study demonstrated that bioactive constituents and targets bind with favorable binding affinity. These findings demonstrate the potential of Nyctanthes arbor-tristis in exerting anti-arthritic effects, as supported by in vitro and in silico studies. Further mechanistic research is necessary to validate the therapeutic potential of all phytoconstituents in RA treatment.

The Role of Resection of the Outer Table of the Cranium in Locally Invasive Primary Squamous Cell Carcinoma of the Scalp.

INTRODUCTION: Nonmelanoma skin cancer is the most common malignancy of the scalp. Of these, squamous cell carcinoma (SCC) is the most troublesome. It poses a challenge to the surgeons caring for these patients as the anatomy of the scalp makes excision and reconstruction difficult. Although more superficial lesions are amenable to Mohs micrographic surgery, more invasive lesions require a different approach. This manuscript is a retrospective review of outer table resection for SCC of the scalp invading to the depth of the pericranium. We include a discussion of full thickness craniectomy for invasive SCC, regardless of depth of invasion, for completeness. METHODS: IRB approval was obtained from St. Joseph's Hospital and Medical Center in Phoenix, Arizona. One hundred four potential cases identified based on ICD codes. Ultimately, 23 cases met study criteria and were included in this analysis. Seventeen cases of outer table resection and 6 cases of full craniectomy were discussed. Additionally, the authors' approach for resection and reconstruction is articulated. RESULTS: Seventeen patients underwent outer table resection at an average age of 79.3 years. All had invasion of the pericranium with a mean surface area of 42.6 cm 2 . Eight patients had prior radiation treatment for SCC of the scalp and 12 patients had at least 1 prior surgery to attempt excision of their lesions. Two patients had local recurrence for a local control rate of 88.2% (15/17). One patient with metastasis prior to presentation, died 6 months after his initial surgery for disease-free survival rate of 94.1% (16/17) at a mean of 15.4months. Thirteen patients were able to achieve immediate reconstruction with local flaps with or without additional skin grafting (76.5%). DISCUSSION: The data in this study supports that in instances of locally invasive primary SCC of the scalp that extends to the pericranium, excision down to the calvarium with complete circumferential and deep peripheral margin assessment, followed by resection of the outer table, is an excellent option. The low rate of local recurrence and high disease-free survival in this study support that this method allows for optimal oncologic outcome while mitigating the significant morbidity associated with the alternative option of a full thickness craniectomy.

Mycobacterium fortuitum fabG4 knockdown studies: Implication as pellicle and biofilm specific drug target.

The fatty acid biosynthesis pathway is crucial for the formation of the mycobacterial cell envelope. The fatty acid synthase type-II (FAS-II) components are attractive targets for designing anti-biofilm inhibitors. Literature review, bioinformatics analysis, cloning, and sequencing led to the identification of a novel Mycobacterium fortuitum FAS-II gene MFfabG4 which interacts with mycobacterial proteins involved in biofilm formation. A manually curated M. fortuitum fatty acid biosynthesis pathway has been proposed exploiting functional studies from the Kyoto Encyclopedia of Genes and Genomes and Mycobrowser databases for MFFabG4. M. fortuitum MFfabG4 knockdown strain (FA) was constructed and validated by quantitative polymerase chain reaction. The FA strain displayed unstructured smooth colony architecture, correlating with decreased pathogenicity and virulence. MFfabG4 knockdown resulted in diminished pellicle and attenuated biofilm formation, along with impaired sliding motility, and reduced cell sedimentation. The FA strain showed lowered cell surface hydrophobicity, indicating attenuation in M. fortuitum intracellular infection-causing ability. Stress survival studies showed the requirement of MFfabG4 for survival in a nutrient-starved environment. The results indicate that MFfabG4 maintains the physiology of the cell envelope and is required for the formation of M. fortuitum pellicle and biofilm. The study corroborates the role of MFfabG4 as a pellicle- and biofilm-specific drug target and a potential diagnostic marker for M. fortuitum and related pathogenic mycobacteria.

Pyruvate kinase M2 in chronic inflammations: a potpourri of crucial protein-protein interactions.

Chronic inflammation (CI) is a primary contributing factor involved in multiple diseases like cancer, stroke, diabetes, Alzheimer's disease, allergy, asthma, autoimmune diseases, coeliac disease, glomerulonephritis, sepsis, hepatitis, inflammatory bowel disease, reperfusion injury, and transplant rejections. Despite several expansions in our understanding of inflammatory disorders and their mediators, it seems clear that numerous proteins participate in the onset of CI. One crucial protein pyruvate kinase M2 (PKM2) much studied in cancer is also found to be inextricably woven in the onset of several CI's. It has been found that PKM2 plays a significant role in several disorders using a network of proteins that interact in multiple ways. For instance, PKM2 forms a close association with epidermal growth factor receptors (EGFRs) for uncontrolled growth and proliferation of tumor cells. In neurodegeneration, PKM2 interacts with apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) to onset Alzheimer's disease pathogenesis. The cross-talk of protein tyrosine phosphatase 1B (PTP1B) and PKM2 acts as stepping stones for the commencement of diabetes. Perhaps PKM2 stores the potential to unlock the pathophysiology of several diseases. Here we provide an overview of the notoriously convoluted biology of CI's and PKM2. The cross-talk of PKM2 with several proteins involved in stroke, Alzheimer's, cancer, and other diseases has also been discussed. We believe that considering the importance of PKM2 in inflammation-related diseases, new options for treating various disorders with the development of more selective agents targeting PKM2 may appear.

Role of extreme weather events and El Niño Southern Oscillation on incidence of Enteric Fever in Ahmedabad and Surat, Gujarat, India.

INTRODUCTION: Enteric Fever (EF) affects over 14.5 million people every year globally, with India accounting for the largest share of this burden. The water-borne nature of the disease makes it prone to be influenced as much by unsanitary living conditions as by climatic factors. The detection and quantification of the climatic effect can lead to improved public health measures which would in turn reduce this burden. METHODOLOGY: We obtained a list of monthly Widal positive EF cases from 1995 to 2017 from Ahmedabad and Surat Municipalities. We obtained population data, daily weather data, and Oceanic Niño Index values from appropriate sources. We quantified the association between extreme weather events, phases of El Niño Southern Oscillations (ENSO) and incidence of EF. RESULTS: Both cities showed a seasonal pattern of EF, with cases peaking in early monsoon. Risk of EF was affected equally in both cities by the monsoon season -- Ahmedabad (35%) and Surat (34%). Extreme precipitation was associated with 5% increase in EF in Ahmedabad but not in Surat. Similarly, phases of ENSO had opposite effects on EF across the two cities. In Ahmedabad, strong El Niño months were associated with 64% increase in EF risk while strong La Niña months with a 41% reduction in risk. In Surat, strong El Niño was associated with 25% reduction in risk while moderate La Niña with 21% increase in risk. CONCLUSIONS: Our results show that the risk of EF incidence in Gujarat is highly variable, even between the two cities only 260 kms apart. In addition to improvements in water supply and sewage systems, preventive public health measures should incorporate variability in risk across season and phases of ENSO. Further studies are needed to characterize nationwide heterogeneity in climate-mediated risk, and to identify most vulnerable populations that can benefit through early warning systems.

Response surface modeling integrated microtiter plate assay for Mycobacterium fortuitum biofilm quantification.

In this study, the effects of agitation, temperature, and pH on biofilm formation by Mycobacterium fortuitum were studied and quantified through response surface modeling. The microtiter plate assay was optimized to achieve conditions favoring maximum mycobacterial biofilm quantification. Optical density (OD) measurement using a crystal violet assay was performed to estimate the amount of biofilm formed. Response surface methodology (RSM) results revealed an R2 value of 96.18%, exhibiting a maximum OD of 2.119 (λ570 nm) at a temperature of 37 °C and pH 7.0, under a static environment. The conditions were experimentally validated. Statistically significant results showed that the maximum biofilm was produced 96 h after mycobacterial inoculation. Thus, the results provide a basis for using RSM as an efficient optimization method for M. fortuitum biofilm assays. This approach can also be incorporated into strategies for screening anti-biofilm compounds, synthetic chemicals, drugs, or inhibitors against pathogenic mycobacteria.

Indoor water end-use pattern and its prospective determinants in the twin cities of Gujarat, India: Enabling targeted urban water management strategies.

Water end-use studies disaggregate the quantity and frequency of water uses for various household purposes. Water end-use studies are available but none for India, which is gradually approaching a water-scarce condition from being a water-stressed country at present. This implies a need for incorporating water end-use understanding for augmenting urban recycling plans and strategies. To identify socio-demographic determinants of water end-use consumption for use in targeted urban water management, we focused on the indoor micro-components of bathing, dish-washing, laundering, and cleaning at households across the twin cities of Gujarat, a water-scarce province of India. A mixed-method approach was used for data collection in which questionnaire surveys (estimated or indirect measurements) were coupled with water meters (direct measurements) at households. The twin cities of Gujrat represent a spatial variation in greywater production at homes even at a distance of 30-40 km. Direct measurement showed less total average water consumption in Ahmedabad (83 L/HH/d) than Gandhinagar (105 L/HH/d), while indirect measurement showed indoor average consumption of 427 and 497 L/HH/d in the respective cities. Statistical significance of income, family size, and education was noticed on the water consumption pattern of a household. Besides, the study provides the attitude and practice of users towards water conservation behavior. We present new insights and recommendations for future urban water sustainability that are specific to India and applicable to several south-Asian countries.

Soil properties changes earthworm diversity indices in different agro-ecosystem.

BACKGROUND: Earthworm communities are generally very sensitive to physico-chemical properties of the soil in different agro-ecosystem i.e. cultivated or non-cultivated which directly or indirectly influence the earthworm survival. The difference in physico-chemical properties of soil at different sites contributed to the formation of population patches for earthworm species. Understanding the physico-chemical properties of soil at a particular site could facilitate the prediction of earthworm species at that site. The objective of the present study was to investigate the diversity, abundance, and distribution of earthworms in cultivated and non-cultivated agroecosystems and their physico-chemical properties affecting the earthworm diversity and abundance. RESULTS: Total 10 species of earthworms i.e. Amynthas alexandri, Amynthas morrisi, Eutyphoeus incommodus, Eutyphoeus waltoni, Metaphire birmanica, Metaphire houlleti, Metaphire posthuma, Octochaetona beatrix, Perionyx excavatus, and Polypheretima elongata, were reported. Out of all the reported species, Metaphire posthuma was found to be the most abundant earthworm species in both cultivated and non-cultivated agroecosystems with the occurrence at 56.81% sites. The Shannon-Wiener index (H), Margalef species richness index (DMg) and Pielou species evenness (E) was ranged from 0 to 0.86, 0 to 0.64 and 0.78 to 1 respectively. The principal component analysis resulted in four principal components i.e. PC1, PC2, PC3 and PC4 which contributing variance (%) of 22.96, 19.37, 14.23 and 10.10 respectively. The principal component analysis also showed that physico-chemical parameters of soil such as EC, pH, TDS, texture, OC, moisture, etc. play a critical role in earthworm distribution. CONCLUSION: The conventional farming system has a negative effect on the earthworm diversity in the soil while the physico-chemical properties of soil also have a determinant effect on the same. Earthworms abundance in the present study have significant direct relation with soil properties at a particular site and vice versa. The diversity indices also change due to the conventional farming system which directly affects the earthworm abundance.

Rotavirus Degrades Multiple Interferon (IFN) Type Receptors To Inhibit IFN Signaling and Protects against Mortality from Endotoxin in Suckling Mice.

STAT1 phosphorylation in response to exogenous interferon (IFN) administration can be inhibited by rotaviral replication both in vitro and in vivo In addition many rotavirus strains are resistant to the actions of different IFN types. The regulation by rotaviruses (RVs) of antiviral pathways mediated by multiple IFN types is not well understood. In this study, we find that during infection in vitro and in vivo, RVs significantly deplete IFN type I, II, and III receptors (IFNRs). Regulation of IFNRs occurred exclusively within RV-infected cells and could be abrogated by inhibiting the lysosomal-endosomal degradation pathway. In vitro, IFNR degradation was conserved across multiple RV strains that differ in their modes of regulating IFN induction. In suckling mice, exogenously administered type I, II, or III IFN induced phosphorylation of STAT1-Y701 within intestinal epithelial cells (IECs) of suckling mice. Murine EW strain RV infection transiently activated intestinal STAT1 at 1 day postinfection (dpi) but not subsequently at 2 to 3 dpi. In response to injection of purified IFN-α/ß or -λ, IECs in EW-infected mice exhibited impaired STAT1-Y701 phosphorylation, correlating with depletion of different intestinal IFNRs and impaired IFN-mediated transcription. The ability of EW murine RV to inhibit multiple IFN types led us to test protection of suckling mice from endotoxin-mediated shock, an outcome that is dependent on the host IFN response. Compared to mortality in controls, mice infected with EW murine RV were substantially protected against mortality following parenteral endotoxin administration. These studies identify a novel mechanism of IFN subversion by RV and reveal an unexpected protective effect of RV infection on endotoxin-mediated shock in suckling mice.IMPORTANCE Antiviral functions of types I, II, and III IFNs are mediated by receptor-dependent activation of STAT1. Here, we find that RV degrades the types I, II, and III IFN receptors (IFNRs) in vitro In a suckling mouse model, RV effectively blocked STAT1 activation and transcription following injection of different purified IFNs. This correlated with significantly decreased protein expression of intestinal types I and II IFNRs. Recent studies demonstrate that in mice lipopolysaccharide (LPS)-induced lethality is prevented by genetic ablation of IFN signaling genes such as IFNAR1 and STAT1. When suckling mice were infected with RV, they were substantially protected from lethal exposure to endotoxin. These findings provide novel insights into the mechanisms underlying rotavirus regulation of different interferons and are likely to stimulate new research into both rotavirus pathogenesis and endotoxemia.

Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma.

The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval [CI] 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to "not reached"). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692).

Internal root resorption in permanent mandibular molars - A rare entity: Report of two cases.

The cases presented here aim to highlight the occurrence of a very rare internal root resorption (IRR) of inflammatory type among mandibular molars (prevalence 0.01%-1%). Patients reported in the outpatient department with a chief complaint of pain in the lower posterior region of the jaws, on thorough clinical and radiological examinations a diagnosis of irreversible pulpitis was made and nonsurgical root canal treatment was planned using thermoplastic obturation technique along with the use of magnification, cone-beam computed tomography, endosonics, and intracanal medicament to attain a successful outcome. Six-month follow-up showed arrest of IRR. This report of two cases with a literature review discusses the etiology, prevalence of IRR, the clinical decision, and the therapeutic management. Early detection of such resorption is the key to successful management and preserves the integrity of the tooth.

Human-Derived collagen hydrogel as an antibiotic vehicle for topical treatment of bacterial biofilms.

The complexity of chronic wounds creates difficulty in effective treatments, leading to prolonged care and significant morbidity. Additionally, these wounds are incredibly prone to bacterial biofilm development, further complicating treatment. The current standard treatment of colonized superficial wounds, debridement with intermittent systemic antibiotics, can lead to systemic side-effects and often fails to directly target the bacterial biofilm. Furthermore, standard of care dressings do not directly provide adequate antimicrobial properties. This study aims to assess the capacity of human-derived collagen hydrogel to provide sustained antibiotic release to disrupt bacterial biofilms and decrease bacterial load while maintaining host cell viability and scaffold integrity. Human collagen harvested from flexor tendons underwent processing to yield a gellable liquid, and subsequently was combined with varying concentrations of gentamicin (50-500 mg/L) or clindamycin (10-100 mg/L). The elution kinetics of antibiotics from the hydrogel were analyzed using liquid chromatography-mass spectrometry. The gel was used to topically treat Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium perfringens in established Kirby-Bauer and Crystal Violet models to assess the efficacy of bacterial inhibition. 2D mammalian cell monolayers were topically treated, and cell death was quantified to assess cytotoxicity. Bacteria-enhanced in vitro scratch assays were treated with antibiotic-embedded hydrogel and imaged over time to assess cell death and mobility. Collagen hydrogel embedded with antibiotics (cHG+abx) demonstrated sustained antibiotic release for up to 48 hours with successful inhibition of both MRSA and C. perfringens biofilms, while remaining bioactive up to 72 hours. Administration of cHG+abx with antibiotic concentrations up to 100X minimum inhibitory concentration was found to be non-toxic and facilitated mammalian cell migration in an in vitro scratch model. Collagen hydrogel is a promising pharmaceutical delivery vehicle that allows for safe, precise bacterial targeting for effective bacterial inhibition in a pro-regenerative scaffold.

Successful topical treatment of human biofilms using multiple antibiotic elution from a collagen-rich hydrogel.

Chronic non-healing wounds significantly strain modern healthcare systems, affecting 1-2% of the population in developed countries with costs ranging between $28.1 and $96.8 billion annually. Additionally, it has been established that chronic wounds resulting from comorbidities, such as peripheral vascular disease and diabetes mellitus, tend to be polymicrobial in nature. Treatment of polymicrobial chronic wounds with oral and IV antibiotics can result in antimicrobial resistance, leading to more difficult-to-treat wounds. Ideally, chronic ulcers would be topically treated with antibiotic combinations tailored to the microbiome of a patient's wound. We have previously shown that a topical collagen-rich hydrogel (cHG) can elute single antibiotics to inhibit bacterial growth in a manner that is nontoxic to mammalian cells. Here, we analyzed the microbiology of cultures taken from human patients diagnosed with diabetes mellitus suffering from chronic wounds present for more than 6 weeks. Additionally, we examined the safety of the elution of multiple antibiotics from collagen-rich hydrogel in mammalian cells in vivo. Finally, we aimed to create tailored combinations of antibiotics impregnated into cHG to successfully target and treat infections and eradicate biofilms cultured from human chronic diabetic wound tissue. We found that the majority of human chronic wounds in our study were polymicrobial in nature. The elution of multiple antibiotics from cHG was well-tolerated in mammalian cells, making it a potential topical treatment of the polymicrobial chronic wound. Finally, combinations of antibiotics tailored to each patient's microbiome eluted from a collagen-rich hydrogel successfully treated bacterial cultures isolated from patient samples via an in vitro assay.

Spatial analysis of food and water-borne diseases in Ahmedabad, India: Implications for urban public health planning.

Spatial analysis of infectious diseases can play an important role in mapping the spread of diseases and can support policy making at local level. Moreover, identification of disease clusters based on local geography and landscape forms the basis for disease control and prevention. Therefore, this study aimed to examine the spatial-temporal variations, hotspot areas, and potential risk factors of infectious diseases (including Viral Hepatitis, Typhoid and Diarrhea) in Ahmedabad city of India. We used Moran's I and Local Indicators of Spatial Association (LISA) mapping to detect spatial clustering of diseases. Spatial and temporal regression analysis was used to identify the association between disease incidence and spatial risk factors. The Moran's I statistics identified presence of positive spatial autocorrelation within the considered diseases, with Moran's I from 0.09 for typhoid to 0.21 for diarrhea (p < 0.001). This indicates a clustering of affected wards for each disease, suggesting that cases were not randomly distributed across the city. LISA mapping demonstrated the clustering of hotspots in central regions of the city, especially towards the east of the river Sabarmati, highlighting key geographical areas with elevated disease risk. The spatial clusters of infectious diseases were consistently associated with slum population density and illiteracy. Furthermore, temporal analysis suggested illiteracy rates could increase risk of viral hepatitis by 13 % (95 % Confidence Interval (CI): 1.01-1.26) and of diarrhea by 18 % (95 % CI: 1.07-1.31). Significant inverse association was also seen between viral hepatitis incidence and the distance of wards from rivers. Conclusively, the study highlight the impact of socio-economic gradients, such as slum population density (indicative of poverty) and illiteracy, on the localized transmission of water and foodborne infections. The evident social stratification between impoverished and affluent households emerges as a notable contributing factor and a potential source of differences in the dynamics of infectious diseases in Ahmedabad.

Inflammatory Cytokines in Rheumatoid Arthritis: Diagnostic Challenges, Pathogenic Mechanisms and their Role in Depression and Management.

Depression being a common comorbidity of rheumatoid arthritis (RA) is found to be responsible for the reduction in the lifespan of the sufferer along with the compromised quality of life. The study quoted below highlights the pathogenic pathways, the frequency of RA along with its impact on patients, thus, raising awareness about the concerned topic. It is found that the chances and frequency of developing depression are 2-3 times higher in patients with RA in comparison to the general population. For such studies, self-reported questionnaires along with proper screening of inclusion and exclusion criteria have been employed which helped in a better comparative study of the topic. As per a report from a meta-analysis, 16.8% of patients with RA have been observed to develop severe depression. According to recent research in the related field, the hypothesis of the role of immune-mediated processes and their role in brain networks and inflammation has been found to be engaged in the progression and pathophysiology of depression in patients with RA. Autoimmune mechanisms and cytokines are found to play an essential role in coordination for initiating and sustaining the disorder. Involvement of IL-1, IL-6 and TNF-α has been studied and analysed widely. A number of studies have shown a connection between depression and RA-related physical impairment, fatigue, and increased pain. Higher mortality, reduced treatment compliance, and more comorbidities effects increased suicide risk. It is also found that depression along with RA leads to hospitalizations, which in turn increase the cost of care for the patient. Hence, it could be stated that the study of depression in RA can be an important marker for the progression of RA and its prognosis. The latest treatment strategies for RA include management of symptoms and early disorder treatment The current review aims to investigate and bring the links between RA and its symptoms into the limelight, including the psycho-social, physiological, and neurological aspects along with their molecular mechanism, for a better discernment of the topic for the readers.