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Reprogramming of macrophages into the inflammatory state (also known as M1) is currently considered as an effective way of eliminating cancer cells, but systemic deployment of this strategy is likely to induce dangerous autoimmune reactions. Consequently, converting immunosuppressive M2-type macrophages into M1 systemically is not a safe and effective therapeutic approach against cancer. Through cleavable covalent linking of curcumin to the chemotherapeutic agent Paclitaxel (Taxol), we have created a novel prodrug (STO-1) that, upon intravenous delivery, selectively reprograms tumor-associated microglia and macrophages (TAMs) and eliminates glioblastoma (GBM) without triggering autoimmunity. Demonstrating its therapeutic efficacy, prolonged treatment of six orthotopic GBM-bearing mice with STO-1 resulted in 67% long-term survival, with three surviving mice exhibiting complete tumor clearance and one displaying minimal residual disease, as confirmed by high-resolution ex vivo T2-weighted MRI 85 days after tumor inoculation. In contrast, the vehicle-treated mice displayed extensive intracranial tumors with edema and hemorrhage. Mechanistically, scRNA-seq analysis indicated induction of multiple M1-associated transcripts (ccrl2, cxcl9, ccr2, ccl5) consistent with robust TAMs reprogramming. In striking contrast to the M2⟶M1 reprogramming of TAMs, M1-type macrophages were suppressed in the spleens of STO-1-treated cancer-free mice. Therefore, STO-1 induces selective anti-tumor immunity and GBM elimination without triggering systemic autoimmune reactions.

Human retrotransposon insertions are often associated with diseases. In the case of the neurodegenerative X-Linked Dystonia-Parkinsonism disease, a human-specific SINE-VNTR- subfamily F retrotransposon was inserted in intron 32 of the gene. Here, we genomically rewrote a portion of the mouse allele with the corresponding 78-kb XDP patient derived allele. In mESCs, the presence of the intronic SVAs-rather than the hybrid gene structure-reduces hy levels. This leads to transcriptional downregulation of genes with TATA box enriched in their promoters and triggering apoptosis. Chromatin and transcriptome profiling revealed that intronic SVAs are actively transcribed, forming barriers that likely impede transcription elongation. In mice, neuronal lineage humanization resulted lethality of male progeny within two months. XDP male mice had severe atrophy centered on the striatum-the same affected brain region in XDP patients. Lastly, CRISPRa-mediated activation of hy restored mESC viability, suggesting boosting transcription as a therapeutic approach.

[...]we saw parts of the city and had experiences we otherwise would have yet to discover. [...]many of my friends in residence complained that being drunk all the time actually hindered the process of making friends. [...]Rad Frosh, organized and funded through McGill's Quebec Public Interest Research Group & Mdash;whose aim is to provide a 'radical' alternative to regular orientation activities by means of social-justice based programming& Mdash;was a great alternative.

Geopolymer concrete (GPC) offers a sustainable alternative by eliminating the need for cement, thereby reducing carbon dioxide emissions. Using durable concrete helps prevent the corrosion of reinforcing bars and reduces spalling caused by chemical attacks. This study investigates the impact of adding 5, 10, and 15% silica fumes (SF) on the mechanical and durability properties of GPC cured at 60 °C for 24 h. In the research, concrete specimens were submerged continuously for 62 days in four different chemicals: 6% sodium sulfate, 6% sodium chloride, 2% sulfuric acid, and 2% hydrochloric acid. The study assessed the effects of chemical exposure on concrete properties by examining water absorption, sorptivity, and compressive strength loss in GPC specimens. Maximum compressive strength, split tensile strength, and flexural strength of about 48.35 MPa, 4.91 MPa, and 5.01 MPa are achieved after incorporation of 10% SF in GPC after 28 days of curing. Results indicated that GPC with a significant dosage of SF (10%) improves its mechanical and durability properties. The maximum rebound number and ultrasonic pulse velocity are achieved after 90 days of curing with a 10% dosage of SF. Moreover, an economic analysis was conducted to confirm the economic viability.

Homocystinuria is a rare metabolic inborn disorder caused due to dysfunctional cystathionine β-synthase (CBS) enzyme activity, thus resulting in elevated levels of methionine and homocysteine in the blood and urine. The timely recognition of this rare metabolic disorder and prompt methionine-restricted diet are crucial in lessening the systemic consequences. The recalcitrant cases have a higher risk for cardiovascular diseases, neurodegenerative diseases, neural tube defects, and other severe clinical complications. This review aims to present the ophthalmic spectrum of homocystinuria and its molecular basis, the disease management, as well as the current and potential treatment approaches with a greater emphasis on preventive strategies.

Arsenic poisoning through groundwater is the world’s greatest normal groundwater catastrophe which got an immense effect on worldwide general wellbeing. India is confronting the outcomes of arsenic poisoning in the zone of Ganga Brahmaputra alluvial plains. In Bihar, out of 38 districts, 18 districts are exceptionally influenced with groundwater arsenic defilement. In the present study, we have assessed the current situation of arsenic exposure in Sabalpur village of Saran district of Bihar after reporting of breast, renal, skin and thyroid cancer cases from this village along with typical symptoms of arsenicosis. Such cancer patients were identified at our institute and were taken for the study. The present investigation deals with the quantification of arsenic in groundwater, hair and nail samples of subjects as well as the survey of entire village to know the overall health status of the village people. A total of n=128 household handpump water samples as well as n=128 human hair and nail samples were collected from over n=520 households. Using the graphite furnace atomic absorption spectrophotometer (GF-AAS), all the samples were analysed. The investigation resulted that the 61% of the analysed samples particularly the groundwater had the arsenic levels more than the permissible limit of WHO (> 10 μg/L) with 244.20 μg/L as the highest arsenic contamination in one of the handpump water sample. The exposure effect of hair sample was worst as 88% of all the collected samples were having high arsenic levels more than the permissible limit (> 0.2 mg/Kg). In case of nail samples, 92% of the samples were having high arsenic concentration more than the permissible limit (> 0.5 mg/Kg). The health survey study revealed high magnitude of disease burden in the exposed population with symptoms such as asthma, anaemia, hepatomegaly, diabetes, cardiac problem, skin fungal infections, breathlessness and mental disability. Few cancer cases of renal, skin, breast and cervix were also found among the exposed population of this village. The percentage of cancer cases in this village was 0.94% that was low, but it would be an aggravated situation in the near future if people will continue drinking arsenic-contaminated water. Therefore, a mitigation intervention was carried out in March 2020 by installing an arsenic filter plant. The health situation in the village in the present scenario is hope to improve in the coming years. However, motivation and awareness among the village population are still required.

There has been a rapid growth in the use of automatic decision-making systems and tools in the medical domain. By using the concepts of big data, deep learning, and machine learning, these systems extract useful information from large medical datasets and help physicians in making accurate and timely decisions regarding predictions and diagnosis of diseases. In this regard, this study provides an extensive review of the progress of applying Artificial Intelligence in forecasting and detecting liver diseases and then summarizes related limitations of the studies followed by future research.

Background Policymakers need regular high-quality coverage data on care around the time of birth to accelerate progress for ending preventable maternal and newborn deaths and stillbirths. With increasing facility births, routine Health Management Information System (HMIS) data have potential to track coverage. Identifying barriers and enablers faced by frontline health workers recording HMIS source data in registers is important to improve data for use. Methods The EN-BIRTH study was a mixed-methods observational study in five hospitals in Bangladesh, Nepal and Tanzania to assess measurement validity for selected Every Newborn coverage indicators. We described data elements required in labour ward registers to track these indicators. To evaluate barriers and enablers for correct recording of data in registers, we designed three interview tools: a) semi-structured in-depth interview (IDI) guide b) semi-structured focus group discussion (FGD) guide, and c) checklist assessing care-to-documentation. We interviewed two groups of respondents (January 2018–March 2019): hospital nurse-midwives and doctors who fill ward registers after birth ( n  = 40 IDI and n  = 5 FGD); and data collectors ( n  = 65). Qualitative data were analysed thematically by categorising pre-identified codes. Common emerging themes of barriers or enablers across all five hospitals were identified relating to three conceptual framework categories. Results Similar themes emerged as both barriers and enablers. First, register design was recognised as crucial, yet perceived as complex, and not always standardised for necessary data elements. Second, register filling was performed by over-stretched nurse-midwives with variable training, limited supervision, and availability of logistical resources. Documentation complexity across parallel documents was time-consuming and delayed because of low staff numbers. Complete data were valued more than correct data. Third, use of register data included clinical handover and monthly reporting, but little feedback was given from data users. Conclusion Health workers invest major time recording register data for maternal and newborn core health indicators. Improving data quality requires standardised register designs streamlined to capture only necessary data elements. Consistent implementation processes are also needed. Two-way feedback between HMIS levels is critical to improve performance and accurately track progress towards agreed health goals.

Temperature-induced, rapid changes in the viscosity and reproducible 3-D structure formation makes thermos-sensitive hydrogels an ideal delivery system to act as a cell scaffold or a drug reservoir. Moreover, the hydrogels’ minimum invasiveness, high biocompatibility, and facile elimination from the body have gathered a lot of attention from researchers. This review article attempts to present a complete picture of the exhaustive arena, including the synthesis, mechanism, and biomedical applications of thermosensitive hydrogels. A special section on intellectual property and marketed products tries to shed some light on the commercial potential of thermosensitive hydrogels.

AimsReduce error in drug prescribing and administration in the Neonatal Unit by 20% by December 2021, from a baseline of 5.7 errors per fortnight.MethodsA live audit on medication errors was maintained by the senior pharmacist from May 2019-July 2021 at a Level 2 neonatal unit in SE London. The data was analyzed retrospectively, showing an average of 5.7 medication errors per fortnight. Of these, 56% of medication errors were due to prescribing, 19% administration, and 24% a mixture of both. Over one-third of medication errors (38.4%) were attributable to aminoglycosides and 21.73% to doses not being signed.The project was launched on 26/08/21 with an aim to reduce the total number of errors by 20%, equating to <=4.48 errors per fortnight. The project team consisted of a lead neonatal consultant, pharmacist, practice developmental nurse, neonatal nurses, junior doctor, and a quality improvement coach. The team used the Model for Improvement as a framework and ideas for change were generated by the team and tested as PDSA cycles. These included regular staff teaching, drug prescribing tests, Pharmacy quiz, Pharmacy based simulations, sharing twice-monthly RED posters cross-site, sharing learning through weekly grand rounds and doctors’ and nursing handovers, nursing tests, red aprons for the nurses during drug administration and an aminoglycoside information leaflet. The senior pharmacist continued to collect prospective data, which were analysed using Statistical Process Control (SPC) charts. Monthly team meetings and ad-hoc huddles were conducted during this period to review the data, any challenges and the efficacy of the ideas tested and feedback was collected.ResultsThere was a significant reduction in medication errors from 5.7 to 3.7 errors per fortnight. Errors in aminoglycoside prescribing and administration reduced from 38% to 17.5% (figures 1 and 2).A peak in incidents was noticed between 9 - 22/12/2021 and a deep dive into the causes revealed significant staff shortages due to sickness and self-isolation corresponding with the Omicron surge. The project team continued to meet until January 2022 to ensure earlier improvements were sustained, which is demonstrated in the data collected.Abstract 1008 Figure 1Abstract 1008 Figure 2ConclusionPrescribing is a complex, challenging task and a high-risk area of clinical practice.1 Preventing prescribing errors is critical to improving patient safety.2 Studies have identified a range of factors underpinning poor prescribing at individual, environmental and organizational levels.3 Through our project, we have demonstrated that these errors can be reduced to a minimum by sheer commitment, effective team engagement, supervision, teaching, and training of the staff. Currently the biggest barrier to sustaining the change are staffing issues within the department and the impact of COVID-19, however going forward embedding the correct culture is paramount.ReferencesDepartment of Health. Building a Safer NHS for Patients. London: NHS, 2001.Bruna Carolina de Araújo. How to Prevent or Reduce Prescribing Errors: An Evidence Brief for Policy. Front Pharmacol. Published online 2019 Jun 12. doi:10.3389/fphar.2019.00439Ross S, Loke YK. Do educational interventions improve prescribing by medical students and junior doctors? A systematic review. Br J Clin Pharmacol 2009; 67: 662–70.