Epigenetic modifiers as inducer of bioactive secondary metabolites in fungi.

Scientists are making efforts to search for new metabolites as they are essential lead molecules for the drug discovery, much required due to the evolution of multi drug resistance and new diseases. Moreover, higher production of known drugs is required because of the ever growing population. Microorganisms offer a vast collection of chemically distinct compounds that exhibit various biological functions. They play a crucial role in safeguarding crops, agriculture, and combating several infectious ailments and cancer. Research on fungi have grabbed a lot of attention after the discovery of penicillin, most of the compounds produced by fungi under normal cultivation conditions are discovered and now rarely new compounds are discovered. Treatment of fungi with the epigenetic modifiers has been becoming very popular since the last few years to boost the discovery of new molecules and enhance the production of already known molecules. Epigenetic literally means above genetics that actually does not alter the genome but alter its expression by altering the state of chromatin from heterochromatin to euchromatin. Chromatin in heterochromatin state usually doesn't express because it is closely packed by histones in this state. Epigenetic modifiers loosen the packing of chromatin by inhibiting DNA methylation and histone deacetylation and thus permit the expression of genes that usually remain dormant. This study delves into the possibility of utilizing epigenetic modifying agents to generate pharmacologically significant secondary metabolites from fungi.

Preoperative Oral Carbohydrate-Containing Fluid Versus Plain Water in Elective Cesarean Deliveries: A Randomized Clinical Trial.

PURPOSE: Traditional prolonged fasting regimens have recently been replaced with guidelines to take carbohydrate-rich clear fluids until 2 hours before surgery. With this study, we wanted to study if the addition of carbohydrates to preoperative oral fluids confers any advantage. DESIGN: Randomized clinical trial. METHODS: The study was conducted at a single center in North India among singleton pregnancies at term, scheduled for elective cesarean section under subarachnoid block. Participants were randomized into 2 groups of 50 participants each. The "Carbohydrate group" received 400 mL of fluid containing 50 g of glucose, while the "plain water" group received 400 mL of water 2 to 4 hours before surgery. A visual analog scale was used to assess hunger, thirst, anxiety, fatigue, and nausea before surgery. Intraoperative mean arterial pressure, hypotension, nausea, and vomiting were noted. On the first postoperative day, recovery from anesthesia was assessed using the Quality of recovery from anesthesia- 40 (QoR-40) questionnaire. Blood sugar levels were compared on the first postoperative day and in cord blood. FINDINGS: Preoperative visual analog scale scores for hunger, thirst, anxiety, nausea, and fatigue were similar in both groups. The occurrence of hypotension (P = .688) and phenylephrine use (P = .39), recovery from anesthesia (P = .92), cord blood sugar levels (P = .24), and postoperative blood sugar levels were also not significantly different in both groups (P = .81). CONCLUSION: This study did not find any significant advantage of preoperative carbohydrate-containing fluid over preoperative plain water in women undergoing elective cesarean delivery under Subarachnoid block.

Nonsurgical Management of High-Risk Lesions.

This article highlights the recent publications and changing trends in practice regarding management of high-risk lesions of the breast. Traditional management has always been a surgical operation but this is recognized as overtreatment. It is recognized that overdiagnosis is inevitable but what we can control is overtreatment. Vacuum-assisted excision is now established as an alternative technique to surgery for further sampling of these high-risk lesions in the United Kingdom. Guidelines from the United Kingdom and Europe now recognize this alternative pathway, and data are available showing that vacuum-assisted excision is a safe alternative to surgery.

Minimally invasive treatment of early, good prognosis breast cancer-is this feasible?

Breast cancer screening programmes frequently detect early, good prognosis breast cancers with significant treatment burden for patients, and associated health-cost implications. Emerging evidence suggests a role for minimally invasive techniques in the management of these patients enabling many women to avoid surgical intervention. Minimally invasive techniques include vacuum-assisted excision, cryoablation, and radiofrequency ablation. We review published evidence in relation to the risks and benefits of each technique and discuss ongoing trials. Data to date are promising, and we predict a trend towards minimally invasive treatment for early, good-prognosis breast cancer as technical skills, suitability criteria, and follow-up protocols are established.

High prevalence of cagA positive Vac A s1m1 Helicobacter pylori strains isolated from patients suffering from various gastroduodenal diseases in Guwahati, Assam, India.

AIM AND BACKGROUND: Genotyping of H. pylori strains was identified on formalin-fixed paraffin wax-embedded tissue (FFPE) sections and correlated with severity grades of gastric mucosal pathologies in biopsies from upper gastrointestinal (UGI) tract from Guwahati, Assam. MATERIALS AND METHODS: In total, 168 gastric biopsies collected from patients with UGI symptoms underwent histological evaluation as per the updated Sydney system. RESULT: H. pylori-like organisms were identified with Warthin and Starry stain, and virulent genes were amplified using polymerase chain reaction (PCR) from genomic DNA extracted from FFPE sections by using QIAamp® DNA FFPE Tissue Kit. Histological examination identified H. pylori-like organisms in 100 biopsies, of which 96 were urease + ve. The prevalence of H. pylori infection was high in age groups 71-80 (88.8%) as compared to other age groups, and it was higher in females (78.9%) when compared to males. The prevalence of virulent genes in biopsies was 88.5% cagA and vacA s1m1, 31.2% iceA1, 32.2% iceA2, and 85.2% babA2. The histological parameters mononuclear cell infiltrate (P = 0.04) and atrophy (P = 0.03), showed statistically significant association with iceA2 and intestinal metaplasia with cagA (P = 0.01) vacAs1m1 (P = 0.01) and babA (P = 0.02) genotypes. Gastric erosion due to H. pylori infection and atrophy showed a significant association. A high bacterial density score was seen with the virulent genotypes. CONCLUSION: Our work reports for the first time a high prevalence (88.5%) of H. pylori cagA vacA s1m1 genotype in Guwahati, Assam. Association of gastric atrophy and intestinal metaplasia was seen with virulent genotypes. Results show the effectiveness of the FFPE kit for DNA extraction in remote areas where transportation and storage of biopsies are otherwise difficult.

The relationship between parameters measured using intravoxel incoherent motion and dynamic contrast-enhanced MRI in patients with breast cancer undergoing neoadjuvant chemotherapy: a longitudinal cohort study.

Purpose: The primary aim of this study was to explore whether intravoxel incoherent motion (IVIM) can offer a contrast-agent-free alternative to dynamic contrast-enhanced (DCE)-MRI for measuring breast tumor perfusion. The secondary aim was to investigate the relationship between tissue diffusion measures from DWI and DCE-MRI measures of the tissue interstitial and extracellular volume fractions. Materials and methods: A total of 108 paired DWI and DCE-MRI scans were acquired at 1.5 T from 40 patients with primary breast cancer (median age: 44.5 years) before and during neoadjuvant chemotherapy (NACT). DWI parameters included apparent diffusion coefficient (ADC), tissue diffusion (Dt), pseudo-diffusion coefficient (Dp), perfused fraction (f), and the product f×Dp (microvascular blood flow). DCE-MRI parameters included blood flow (Fb), blood volume fraction (vb), interstitial volume fraction (ve) and extracellular volume fraction (vd). All were extracted from three tumor regions of interest (whole-tumor, ADC cold-spot, and DCE-MRI hot-spot) at three MRI visits: pre-treatment, after one, and three cycles of NACT. Spearman's rank correlation was used for assessing between-subject correlations (r), while repeated measures correlation was employed to assess within-subject correlations (rrm) across visits between DWI and DCE-MRI parameters in each region. Results: No statistically significant between-subject or within-subject correlation was found between the perfusion parameters estimated by IVIM and DCE-MRI (f versus vb and f×Dp versus Fb; P=0.07-0.81). Significant moderate positive between-subject and within-subject correlations were observed between ADC and ve (r=0.461, rrm=0.597) and between Dt and ve (r=0.405, rrm=0.514) as well as moderate positive within-subject correlations between ADC and vd and between Dt and vd (rrm=0.619 and 0.564, respectively) in the whole-tumor region. Conclusion: No correlations were observed between the perfusion parameters estimated by IVIM and DCE-MRI. This may be attributed to imprecise estimates of fxDp and vb, or an underlying difference in what IVIM and DCE-MRI measure. Care should be taken when interpreting the IVIM parameters (f and f×Dp) as surrogates for those measured using DCE-MRI. However, the moderate positive correlations found between ADC and Dt and the DCE-MRI parameters ve and vd confirms the expectation that as the interstitial and extracellular volume fractions increase, water diffusion increases.

Heterologous expression of Arabidopsis laccase2, laccase4 and peroxidase52 driven under developing xylem specific promoter DX15 improves saccharification in populus.

BACKGROUND: Secondary cell wall holds considerable potential as it has gained immense momentum to replace the lignocellulosic feedstock into fuels. Lignin one of the components of secondary cell wall tightly holds the polysaccharides thereby enhancing the recalcitrance and complexity in the biomass. Laccases (LAC) and peroxidases (PRX) are the major phenyl-oxidases playing key functions during the polymerization of monolignols into lignin. Yet, the functions of laccase and peroxidases gene families remained largely unknown. Hence, the objective of this conducted study is to understand the role of specific LAC and PRX in Populus wood formation and to further investigate how the altered Lac and Prx expression affects biomass recalcitrance and plant growth. This study of heterologous expression of Arabidopsis Lac and Prx genes was conducted in poplar to avoid any otherwise occurring co-suppression mechanism during the homologous overexpression of highly expressed native genes. In the pursuit of optimizing lignocellulosic biomass for biofuel production, the present study focuses on harnessing the enzymatic potential of Arabidopsis thaliana Laccase2, Laccase4, and Peroxidase52 through heterologous expression. RESULTS: We overexpressed selected Arabidopsis laccase2 (AtLac2), laccase4 (AtLac4), and peroxidase52 (AtPrx52) genes, based on their high transcript expression respective to the differentiating xylem tissues in the stem, in hybrid poplar (cv. 717) expressed under the developing xylem tissue-specific promoter, DX15 characterized the transgenic populus for the investigation of growth phenotypes and recalcitrance efficiency. Bioinformatics analyses conducted on AtLac2 and AtLac4 and AtPrx52, revealed the evolutionary relationship between the laccase gene and peroxidase gene homologs, respectively. Transgenic poplar plant lines overexpressing the AtLac2 gene (AtLac2-OE) showed an increase in plant height without a change in biomass yield as compared to the controls; whereas, AtLac4-OE and AtPrx52-OE transgenic lines did not show any such observable growth phenotypes compared to their respective controls. The changes in the levels of lignin content and S/G ratios in the transgenic poplar resulted in a significant increase in the saccharification efficiency as compared to the control plants. CONCLUSIONS: Overall, saccharification efficiency was increased by 35-50%, 21-42%, and 8-39% in AtLac2-OE, AtLac4-OE, and AtPrx52-OE transgenic poplar lines, respectively, as compared to their controls. Moreover, the bioengineered plants maintained normal growth and development, underscoring the feasibility of this approach for biomass improvement without compromising overall plant fitness. This study also sheds light on the potential of exploiting regulatory elements of DX15 to drive targeted expression of lignin-modifying enzymes, thereby providing a promising avenue for tailoring biomass for improved biofuel production. These findings contribute to the growing body of knowledge in synthetic biology and plant biotechnology, offering a sustainable solution to address the challenges associated with lignocellulosic biomass recalcitrance.

Atypia detected during breast screening and subsequent development of cancer: observational analysis of the Sloane atypia prospective cohort in England.

OBJECTIVE: To explore how the number and type of breast cancers developed after screen detected atypia compare with the anticipated 11.3 cancers detected per 1000 women screened within one three year screening round in the United Kingdom. DESIGN: Observational analysis of the Sloane atypia prospective cohort in England. SETTING: Atypia diagnoses through the English NHS breast screening programme reported to the Sloane cohort study. This cohort is linked to the English Cancer Registry and the Mortality and Birth Information System for information on subsequent breast cancer and mortality. PARTICIPANTS: 3238 women diagnosed as having epithelial atypia between 1 April 2003 and 30 June 2018. MAIN OUTCOME MEASURES: Number and type of invasive breast cancers detected at one, three, and six years after atypia diagnosis by atypia type, age, and year of diagnosis. RESULTS: There was a fourfold increase in detection of atypia after the introduction of digital mammography between 2010 (n=119) and 2015 (n=502). During 19 088 person years of follow-up after atypia diagnosis (until December 2018), 141 women developed breast cancer. Cumulative incidence of cancer per 1000 women with atypia was 0.95 (95% confidence interval 0.28 to 2.69), 14.2 (10.3 to 19.1), and 45.0 (36.3 to 55.1) at one, three, and six years after atypia diagnosis, respectively. Women with atypia detected more recently have lower rates of subsequent cancers detected within three years (6.0 invasive cancers per 1000 women (95% confidence interval 3.1 to 10.9) in 2013-18 v 24.3 (13.7 to 40.1) in 2003-07, and 24.6 (14.9 to 38.3) in 2008-12). Grade, size, and nodal involvement of subsequent invasive cancers were similar to those of cancers detected in the general screening population, with equal numbers of ipsilateral and contralateral cancers. CONCLUSIONS: Many atypia could represent risk factors rather than precursors of invasive cancer requiring surgery in the short term. Women with atypia detected more recently have lower rates of subsequent cancers detected, which might be associated with changes to mammography and biopsy techniques identifying forms of atypia that are more likely to represent overdiagnosis. Annual mammography in the short term after atypia diagnosis might not be beneficial. More evidence is needed about longer term risks.

Wound-healing effect of topical nanoemulsion-loaded cream and gel formulations of Hippophae rhamnoides L. (sea buckthorn) fruit oil and their acute dermal toxicity study on female SD rats.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of topical nanoemulsion (NE)-loaded cream and gel formulations of Hippophae rhamnoides L. (sea buckthorn [SBT]) fruit oil for wound healing. MATERIALS AND METHODS: The NE-loaded cream and gel formulations of H. rhamnoides L. (SBT) fruit oil (IPHRFH) were prepared and evaluated for their wound-healing activity on female Sprague-Dawley (SD) rats. They were further divided into groups (seven) and the wound-healing activity was determined by measuring the area of the wound on the wounding day and on the 0th, 4th, 8th, and 10th days. The acute dermal toxicity of the formulations was assessed by observing the erythema, edema, and body weight (BW) of the rats. RESULTS: The topical NE cream and gel formulations of H. rhamnoides L. (SBT) fruit oil showed significant wound-healing activity in female SD rats. The cream formulation of IPHRFH showed 78.96%, the gel showed 72.59% wound contraction on the 8th day, whereas the positive control soframycin (1% w/w framycetin) had 62.29% wound contraction on the 8th day. The formulations also showed a good acute dermal toxicity profile with no changes significantly affecting BW and dermal alterations. CONCLUSIONS: The results of this study indicate that topical NE-loaded cream and gel formulation of H. rhamnoides L. (SBT) fruit oil are safe and effective for wound healing. The formulations showed no signs of acute dermal toxicity in female SD rats.

Cost-Effectiveness Analysis of Digital Breast Tomosynthesis Added to Synthetic Mammography in Breast Cancer Screening in Brazil.

BACKGROUND: Literature meta-analysis results show that digital breast tomosynthesis (DBT) combined with synthesized two-dimensional (s2D) mammograms can reduce recalls and improve breast cancer detection. Uncertainty regarding the screening of patients with breast cancer presents a health economic challenge, both in terms of healthcare resource use and quality of life impact on patients. OBJECTIVE: This study aims to estimate the cost effectiveness of DBT + s2D versus digital mammography (DM) used in a biennial breast cancer screening setting of women aged 40-69 years with scattered areas of fibroglandular breast density and heterogeneous dense breasts in the Brazilian supplementary health system. METHODS: A cost-effectiveness analysis was performed on the basis of clinical data obtained from a systematic review with meta-analysis performed to evaluate the analytical validity and clinical utility of DBT + s2D compared with DM. The search was conducted in the PubMed, Cochrane Library and Embase databases, with the main descriptors of the technology, a comparator, and the clinical condition in question, on 9 June 2022. The hybrid economic model (decision tree plus Markov model) simulated costs and outcomes over a lifetime for women aged 40-69 years with scattered areas of fibroglandular breast density and heterogeneous dense breasts. We analyzed incremental cost-effectiveness ratio (ICER) to measure the incremental cost difference per quality-adjusted life year (QALY) of adding DBT + s2D to breast cancer screening. RESULTS: DBT + s2D incurred a cost saving of € 954.02 per patient, in the time horizon of 30 years, compared with DM, and gained 5.1989 QALYs, which would be considered a dominant intervention. These results were confirmed in sensitivity analyses. CONCLUSION: Switching from DM to biennial DBT + s2D was cost effective. Furthermore, reductions in false-positive recall rates should also be considered in decision making.

How long does it take to read a mammogram? Investigating the reading time of digital breast tomosynthesis and digital mammography.

PURPOSE: To analyse digital breast tomosynthesis (DBT) reading times in the screening setting, compared to 2D full-field digital mammography (FFDM), and investigate the impact of reader experience and professional group on interpretation times. METHOD: Reading time data were recorded in the PROSPECTS Trial, a prospective randomised trial comparing DBT plus FFDM or synthetic 2D mammography (S2D) to FFDM alone, in the National Health Service (NHS) breast screening programme, from January 2019-February 2023. Time to read DBT+FFDM or DBT+S2D and FFDM alone was calculated per case and reading times were compared between modalities using dependent T-tests. Reading times were compared between readers from different professional groups (radiologists and radiographer readers) and experience levels using independent T-tests. The learning curve effect of using DBT in screening on reading time was investigated using a Kruskal-Wallis test. RESULTS: Forty-eight readers interpreted 1,242 FFDM batches (34,210 FFDM cases) and 973 DBT batches (13,983 DBT cases). DBT reading time was doubled compared to FFDM (2.09 ± 0.64 min vs. 0.98 ± 0.30 min; p < 0.001), and DBT+S2D reading was longer than DBT + FFDM (2.24 ± 0.62 min vs. 2.04 ± 0.46 min; p = 0.006). No difference was identified in reading time between radiologists and radiographers (2.06 ± 0.71 min vs. 2.14 ± 0.46 min, respectively; p = 0.71). Readers with five or more years of experience reading DBT were quicker than those with less experience (1.86 ± 0.56 min vs. 2.37 ± 0.65 min; p = 0.008), and DBT reading time decreased after less than 9 months accrued screening experience (p = 0.01). CONCLUSIONS: DBT reading times were double those of FFDM in the screening setting, but there was a short learning curve effect with readers showing significant improvements in reading times within the first nine months of DBT experience. CLINICALTRIALS: gov Identifier: NCT03733106.

Vacuum-assisted excision: a safe minimally invasive option for benign phyllodes tumor diagnosis and treatment-a systematic review and meta-analysis.

Synopsis: This is a systematic review and meta-analysis comparing surgical excision with percutaneous ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of benign phyllodes tumor (PT) using local recurrence (LR) as the endpoint. Objective: To determine the frequency of local recurrence (LR) of benign phyllodes tumor (PT) after ultrasound-guided vacuum-assisted excision (US-VAE) compared to the frequency of LR after surgical excision. Method: A systematic review and meta-analysis [following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard] was conducted by comparing LR in women older than 18 years treated for benign PT by US-VAE compared with local surgical excision with at least 12 months of follow-up. Studies were retrieved from PubMed, Scopus, Web of Science, and Embase. The pooled effect measure used was the odds ratio (OR) of recurrence. Results: Five comparative prospective or retrospective observational studies published between January 1, 1992, and January 10, 2022, comparing surgical excision with percutaneous US-VAE for LR of benign PT met the selection criteria. Four were retrospective observational cohorts, and one was a prospective observational cohort. A total of 778 women were followed up. Of them, 439 (56.4%) underwent local surgical excision, and 339 (43.6%) patients had US-VAE. The median age of patients in the five studies ranged from 33.7 to 39 years; the median size ranged from 1.5 cm to 3.0 cm, and the median follow-up ranged from 12 months to 46.6 months. The needle gauge ranged from 7G to 11G. LR rates were not statically significant between US-VAE and surgical excision (41 of 339 versus 34 of 439; OR 1.3; p = 0.29). Conclusion: This meta-analysis suggests that using US-VAE for the removal of benign PT does not increase local regional recurrence and is a safe minimally invasive therapeutic option. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022309782.

Evidence-informed recommendations on managing breast screening atypia: perspectives from an expert panel consensus meeting reviewing results from the Sloane atypia project.

Evidence-based clinical guidelines are essential to maximize patient benefit and to reduce clinical uncertainty and inconsistency in clinical practice. Gaps in the evidence base can be addressed by data acquired in routine practice. At present, there is no international consensus on management of women diagnosed with atypical lesions in breast screening programmes. Here, we describe how routine NHS breast screening data collected by the Sloane atypia project was used to inform a management pathway that maximizes early detection of cancer and minimizes over-investigation of lesions with uncertain malignant potential. A half-day consensus meeting with 11 clinical experts, 1 representative from Independent Cancer Patients' Voice, 6 representatives from NHS England (NHSE) including from Commissioning, and 2 researchers was held to facilitate discussions of findings from an analysis of the Sloane atypia project. Key considerations of the expert group in terms of the management of women with screen detected atypia were: (1) frequency and purpose of follow-up; (2) communication to patients; (3) generalizability of study results; and (4) workforce challenges. The group concurred that the new evidence does not support annual surveillance mammography for women with atypia, irrespective of type of lesion, or woman's age. Continued data collection is paramount to monitor and audit the change in recommendations.

A large yolk sac malignancy in a girl, an uncommon yet challenging ovarian tumor: A case report.

Key Clinical Message: Yolk sac tumors are rare and malignant germ cell tumors of the ovary occurring in children and young women. Fertility-sparing surgical intervention with adjuvant chemotherapy has shown to improve prognosis. Abstract: We present a case of a 14-year-old girl who presented with the complaints of lower abdominal pain and distention. Her tumor markers were increased, and radiological investigation suggested the diagnosis of malignant left ovarian mass. Histopathology confirmed the diagnosis of Yolk sac tumor. She was subsequently managed with fertility-sparing surgery and adjuvant chemotherapy.

Artificial Intelligence as Supporting Reader in Breast Screening: A Novel Workflow to Preserve Quality and Reduce Workload.

OBJECTIVE: To evaluate the effectiveness of a new strategy for using artificial intelligence (AI) as supporting reader for the detection of breast cancer in mammography-based double reading screening practice. METHODS: Large-scale multi-site, multi-vendor data were used to retrospectively evaluate a new paradigm of AI-supported reading. Here, the AI served as the second reader only if it agrees with the recall/no-recall decision of the first human reader. Otherwise, a second human reader made an assessment followed by the standard clinical workflow. The data included 280 594 cases from 180 542 female participants screened for breast cancer at seven screening sites in two countries and using equipment from four hardware vendors. The statistical analysis included non-inferiority and superiority testing of cancer screening performance and evaluation of the reduction in workload, measured as arbitration rate and number of cases requiring second human reading. RESULTS: Artificial intelligence as a supporting reader was found to be superior or noninferior on all screening metrics compared with human double reading while reducing the number of cases requiring second human reading by up to 87% (245 395/280 594). Compared with AI as an independent reader, the number of cases referred to arbitration was reduced from 13% (35 199/280 594) to 2% (5056/280 594). CONCLUSION: The simulation indicates that the proposed workflow retains screening performance of human double reading while substantially reducing the workload. Further research should study the impact on the second human reader because they would only assess cases in which the AI prediction and first human reader disagree.