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.

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.

Analysis of anti-rheumatic activity of Nyctanthes arbor-tristis via in vivo and pharmacovigilance approaches.

Introduction: Rheumatoid arthritis (RA) is an immune-mediated disease associated with chronic inflammation of numerous joints. Nyctanthes arbor-tristis (NAT) is a traditional remedy for RA, a chronic inflammatory disorder. Aim: The current project aims to demonstrate the role of the NAT extracts in sub-acute toxicity, pharmacovigilance, and anti-rheumatic biomarkers. Method: Hydroethanolic extract (1:1) of plant leaves was prepared by using the reflux method. The safety of the dose was evaluated in Sprague-Dawley rats, and the anti-inflammatory effects of NAT on RA symptoms, including paw volumes, body weight, arthritic index, withdrawal latency, hematology and serological test, radiology, and histopathology, were evaluated in Freund's complete adjuvant (FCA)-induced arthritis Sprague-Dawley rat models. The inflammatory (TNF-α and COX-2) and anti-inflammatory markers (IL-10) were analyzed in control and experimental groups. Result: The study showed that 500 mg/kg BW NAT leaf extract was found to be least toxic without showing any subacute toxicity symptoms. The pharmacovigilance study highlighted the potential side effects of NAT, such as drowsiness, sedation, and lethargy, at high dosages. Treatment with the plant extract mitigated paw edema, restored the immune organ and body weights, and ameliorated the level of blood parameters such as hemoglobin, red blood cells, platelets, white blood cells, aspartate aminotransferase (AST), alanine transaminase (ALT), C-reactive proteins, and rheumatoid factor. Treatment with the plant extracts also reduced the level of cyclooxygenase 2 and TNF-α and increased the level of IL-10 in the serum of arthritic rats dose-dependently. Radiographic analysis of the ankle joint showed an improvement in the hind legs. Histological examination of the ankle joints revealed that the plant extract treatment decreased pannus formation, inflammation, and synovial hyperplasia in arthritic animals. Conclusion: NAT 500 mg/kg could serve as a promising therapeutic option for the treatment of inflammatory arthritis.

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.

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 .

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.

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.

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.

Scoping Review of Hydrogel Therapies in the Treatment of Diabetic Chronic Wounds.

Chronic diabetic wounds are a significant issue that can be treated with topical hydrogel therapies. The aim of this study was to review the different compositions of hydrogel that have been developed and analyze their clinical relevance in the treatment of chronic diabetic wounds. Methods: We conducted a scoping review in which twelve articles were selected for review after applying relevant inclusion and exclusion criteria using a two-reviewer strategy. Data extracted from these studies was used to answer the following research question: What is the composition of hydrogels used to treat chronic diabetic wounds and how effective are they? Results: We analyzed five randomized controlled trials, two retrospective studies, three reviews, and two case reports. Hydrogel compositions discussed included mesenchymal stem cell sheets, carbomer, collagen, and alginate hydrogels, as well as hydrogels embedded with platelet-derived growth factor. Synthetic hydrogels, largely composed of carbomers, were found to have high levels of evidence supporting their wound healing properties, though few articles described their routine use in a clinical setting. Collagen hydrogels dominate the present-day hydrogel market in the clinical treatment of chronic diabetic wounds. The augmentation of hydrogels with therapeutic biomaterials is a new field of hydrogel research, with studies demonstrating promising early in vitro and in vivo animal studies demonstrating promising early results for in vitro and in vivo animal investigations. Conclusions: Current research supports hydrogels as a promising topical therapy in the treatment of chronic diabetic wounds. Augmenting Food & Drug Administration-approved hydrogels with therapeutic substances remains an interesting early area of investigation.

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.

Estimation of effects of extreme temperature on the risk of hospitalisation in Taiwan.

BACKGROUND: Extreme temperatures are triggering and exacerbating hospital admissions and health burdens; however, it is still understudied. Therefore, we evaluated the effects of the average temperature on overall hospitalisation and the average length of hospital stay. METHODS: Daily area-specific age-sex stratified hospitalisation records from 2006 to 2020 were collected from the National Health Research Institutes of Taiwan. The distributed lag non-linear model was used to estimate the area-specific relative risk (RR) and 95% CI associated with daily average temperature. Overall cumulative RR was pooled from area-specific RRs using random effects meta-analysis. Temperature effects of extreme high and low thresholds were also evaluated based on the 99th (32°C) and 5th (14°C) percentiles, respectively. RESULTS: Our findings suggested that the elderly (age ≥65 years) are vulnerable to temperature effects, while differential gender effects are not explicit in Taiwan. A higher risk of in-patient visits was seen among the elderly during extreme low temperatures (RR 1.08; 95% CI 1.04 to 1.11) compared with extreme high temperatures (RR 1.07; 95% CI 1.05 to 1.10). Overall, high-temperature extremes increased the risk of hospitalisation with an RR of 1.05 (95% CI 1.03 to 1.07) among the all-age-sex population in Taiwan. Additionally, lag-specific analysis of the study revealed that high-temperature effects on in-patient visits are effective on the same day of exposure, while cold effects occurred after 0-2 days of exposure. The average length of hospital stays can also increase with high-temperature extremes among age group 41-64 years and the elderly. CONCLUSION: Public health preparedness should consider the increased load on health facilities and health expenditures during extreme temperatures.

Foot Burns and Diabetes: A Systematic Review of Current Clinical Studies and Proposal of a New Treatment Algorithm.

This study aims to systematically identify studies that evaluate lower extremity burn injury in the diabetic population, evaluate their clinical course and patient outcomes, and present a treatment algorithm tailored to diabetic burn patients. Our systematic review of the PubMed and Web of Science databases yielded 429 unique articles. After exclusion and inclusion criteria were applied, 59 articles were selected for evaluation. In diabetic patients, thermal injury was largely a result of decreased awareness and education regarding heat therapies in the context of peripheral neuropathy. All non-case studies found that metrics such as hospital length of stay, ICU admission rates, rates of comorbidity, complication rates, scald injuries, infection rates, and cost of treatment was significantly increased in the diabetic burn population as compared to their nondiabetic counterparts. Where infection was present, microorganisms colonizing diabetic burn wounds were different than those found in the burn wounds of immunocompetent individuals. Operative intervention including split-skin graft, amputation, and debridement were more often utilized in diabetic burn patients. Foot burns in diabetic patients pose unique clinical risks to patients, and as such need to be an alternate treatment protocol to reflect their pathology. Education and training programs are crucial in the prevention of diabetic foot burns to avoid complications, protracted healing, and adverse outcomes. A unique algorithm can guide the unique treatment of this clinical entity.

Quantifying the effects of anomalies of temperature, precipitation, and surface water storage on diarrhea risk in Taiwan.

OBJECTIVES: Diarrheal disease continues to be a significant cause of morbidity and mortality. We investigated how anomalies in monthly average temperature, precipitation, and surface water storage (SWS) impacted bacterial, and viral diarrhea morbidity in Taiwan between 2004 and 2015. METHODS: A multivariate analysis using negative binomial generalized estimating equations was employed to quantify age-specific and cause-specific cases of diarrhea associated with anomalies in temperature, precipitation, and SWS. RESULTS: Temperature anomalies were associated with an elevated rate of all-cause infectious diarrhea at a lag of 2 months, with the highest risk observed in the under-5 age group (incidence rate ratio [IRR], 1.03, 95% confidence interval [CI], 1.01 to 1.07). Anomalies in SWS were associated with increased viral diarrhea rates, with the highest risk observed in the under-5 age group at a 2-month lag (IRR, 1.27; 95% CI, 1.14 to 1.42) and a lesser effect at a 1-month lag (IRR, 1.18; 95% CI, 1.06 to 1.31). Furthermore, cause-specific diarrheal diseases were significantly affected by extreme weather events in Taiwan. Both extremely cold and hot conditions were associated with an increased risk of all-cause infectious diarrhea regardless of age, with IRRs ranging from 1.03 (95% CI, 1.02 to 1.12) to 1.18 (95% CI, 1.16 to 1.40). CONCLUSIONS: The risk of all-cause infectious diarrhea was significantly associated with average temperature anomalies in the population aged under 5 years. Viral diarrhea was significantly associated with anomalies in SWS. Therefore, we recommend strategic planning and early warning systems as major solutions to improve resilience against climate change.

An extended approach to appraise electricity distribution and carbon footprint of bitcoin in a smart city.

A nation cannot sustain a highly productive and efficient population without smart cities. Due to their significant reliance on digital technologies, these cities require a high level of cybercrime protection. Cryptocurrencies have gained significant attention due to their secure and reliable infrastructure. The decentralised cryptocurrency operates in a trust-less environment known as the blockchain, where each network participant has a ledger copy of all transactions. Blockchain technology employs a proven consensus mechanism without requiring establishment of a central authority. But the consensus mechanism requires miner to solve a cryptographic problem by generating random hashes until one of them matches the desired one. This procedure is energy-intensive, and when thousands of miners repeat it to verify a single transaction, a substantial amount of electricity is consumed. Moreover, electricity produces a significant amount of carbon footprint. Patch methodology utilises the data of all hashes created per year and the efficiency of mining hardware over a 10-year period to calculate the Bitcoins energy consumption. Due to a large number of unknown and uncertain factors involved, it is difficult to precisely calculate a single value for electricity consumption and carbon footprint as reported by Patch methodology. The proposed method extends the Patch methodology by adding a maximum and minimum limit to the hardware efficiency as well as the sources of power generation, which can help refine estimates of electricity consumption and carbon emissions for a more accurate picture. Using the proposed methodology, it was estimated that Bitcoin consumed between 38.495 and 120.72 terawatt hours of electricity in 2021 and released between 2.12 and 45.37 million metric tonnes of carbon dioxide. To address the issue of excessive energy consumption and carbon emissions, a significant number of individual miners and mining pools are relocating to energy-intensive regions, such as aluminium mining sites that rely on hydroelectricity for energy generation.

Effects of Ambient Temperature, Relative Humidity, and Precipitation on Diarrhea Incidence in Surabaya.

BACKGROUND: Diarrhea remains a common infectious disease caused by various risk factors in developing countries. This study investigated the incidence rate and temporal associations between diarrhea and meteorological determinants in five regions of Surabaya, Indonesia. METHOD: Monthly diarrhea records from local governmental health facilities in Surabaya and monthly means of weather variables, including average temperature, precipitation, and relative humidity from Meteorology, Climatology, and Geophysical Agency were collected from January 2018 to September 2020. The generalized additive model was employed to quantify the time lag association between diarrhea risk and extremely low (5th percentile) and high (95th percentile) monthly weather variations in the north, central, west, south, and east regions of Surabaya (lag of 0-2 months). RESULT: The average incidence rate for diarrhea was 11.4 per 100,000 during the study period, with a higher incidence during rainy season (November to March) and in East Surabaya. This study showed that the weather condition with the lowest diarrhea risks varied with the region. The diarrhea risks were associated with extremely low and high temperatures, with the highest RR of 5.39 (95% CI 4.61, 6.17) in the east region, with 1 month of lag time following the extreme temperatures. Extremely low relative humidity increased the diarrhea risks in some regions of Surabaya, with the highest risk in the west region at lag 0 (RR = 2.13 (95% CI 1.79, 2.47)). Extremely high precipitation significantly affects the risk of diarrhea in the central region, at 0 months of lag time, with an RR of 3.05 (95% CI 2.09, 4.01). CONCLUSION: This study identified a high incidence of diarrhea in the rainy season and in the deficient developed regions of Surabaya, providing evidence that weather magnifies the adverse effects of inadequate environmental sanitation. This study suggests the local environmental and health sectors codevelop a weather-based early warning system and improve local sanitation practices as prevention measures in response to increasing risks of infectious diseases.

Exploring the potential of endophytes and their metabolites for bio-control activity.

In the current scenario, extensive use of synthetic chemicals in agriculture is creating notable problems such as disease and pest resistance, residues, yield loss, and soil unproductiveness. These harmful chemicals are eventually reaching our food plate through bioaccumulation and biomagnification in a crop. As a result, beneficial microorganisms are regularly being explored as a safer option in the agriculture sector for their ability to produce valuable bioactive secondary metabolites, particularly for crop protection. Such natural (bio) products are harmless to plants, humans, and the environment. In our quest for the search of the sources of bioactive constituents from the microorganisms, endophytes are the front-runner. They mutually reside inside the plant providing support against phytopathogens by releasing an array of bioactive secondary metabolites building climate reliance of the host plant. The purpose of this review is to examine the biocontrol potential of endophytes against bacterial and fungal pathogens in sustainable agriculture. We also attempt to explain the structure and activity of the secondary metabolites produced by bacterial and fungal endophytes in conjunction with their biocontrol function. Additionally, we address potential future research directions for endophytes as biopesticides.

Distribution, biosynthesis and therapeutic potential of lignans.

Lignans have long been known for their abundant therapeutic properties due to their polyphenolic structure. Linseed is the richest plant source of lignans and has been studied widely for their properties. The most prevalent lignan, secoisolariciresinol diglucoside (SDG), is consumed with linseed and converted into mammalian lignans, enterodiol (END) and enterolactone (ENL), by the gut microbiota. SDG can easily be assessed using HPLC and its deglycosylated form viz secoisolariciresinol can be asses using GC-MS techniques. Variety of extraction and analysis methods has been reported for plant lignans. SDG is known to have therapeutic properties including anti-oxidant, anti-cancerous, anti-inflammatory, modulation of gene expression, anti-diabetic, estrogenic and anti-estrogenic. Despite a large number of bioactivities, strong evidences for the underlying mechanisms for most of the properties are still unknown. SDG is most studied for its anti-cancerous properties. But the use of lignans as anti-carcinogenic agent is limited and commercially not reported due to challenges of purification at commercial level, rapid metabolism, untargeted delivery and toxic compounds associated with lignans. Exploration of more prominent and active derivatives of SDG and their targeted drug delivery should be an important research toward the use of bioactive lignans of linseed.

A Machine Learning and Deep Learning Approach for Recognizing Handwritten Digits.

Optical character recognition (OCR) can be a subcategory of graphic design that involves extracting text from images or scanned documents. We have chosen to make unique handwritten digits available on the Modified National Institute of Standards and Technology website for this project. The Machine Learning and Depp Learning algorithms are used in this project to measure the accuracy of handwritten displays of letters and numbers. Also, we show the classification accuracy comparison between them. The results showed that the CNN classifier achieved the highest classification accuracy of 98.83%.

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.