Harnessing nature's potential: Alpinia galanga methanolic extract mediated green synthesis of silver nanoparticle, characterization and evaluation of anti-neoplastic activity.

With the advent of nanotechnology, the treatment of cancer is changing from a conventional to a nanoparticle-based approach. Thus, developing nanoparticles to treat cancer is an area of immense importance. We prepared silver nanoparticles (AgNPs) from methanolic extract of Alpinia galanga rhizome and characterized them by UV-Vis spectrophotometry, Fourier transform Infrared (FTIR) spectroscopy, Zetasizer, and Transmission electron Microscopy (TEM). UV-Vis spectrophotometry absorption spectrum showed surface plasmon between 400 and 480 nm. FTIR spectrum analysis implies that various phytochemicals/secondary metabolites are involved in the reduction, caping, and stabilization of AgNPs. The Zetasier result suggests that the particles formed are small in size with a low polydispersity index (PDI), suggesting a narrow range of particle distribution. The TEM image suggests that the particles formed are mostly of spherical morphology with nearly 20-25 nm. Further, the selected area electron diffraction (SAED) image showed five electron diffraction rings, suggesting the polycrystalline nature of the particles. The nanoparticles showed high anticancer efficacy against cervical cancer (SiHa) cell lines. The nanostructures showed dose-dependent inhibition with 40% killing observed at 6.25 µg/mL dose. The study showed an eco-friendly and cost-effective approach to the synthesis of AgNPs and provided insight into the development of antioxidant and anticancer agents.

COVID-19 Is Associated With a 4 Fold Increase in 30-day Mortality Risk in Hip Fracture Patients in the United Kingdom: A Systematic Review and Meta-analysis.

Background: Hip fracture in elderly patients is associated with a significant mortality which may be worsened by COVID-19 infection. Objective: To undertake a systematic review and meta-analysis of studies assessing the effect of COVID-19 infection and mortality rates in hip fracture patients in the United Kingdom (UK) during the first surge of the pandemic. Design: A systematic literature search of 9 online databases was undertaken independently by 2 reviewers using the Cochrane methodology for systematic reviews. Eligibility criteria were any study of an adult population with a hip fracture that assessed the relationship between COVID-19 infection and 30-day mortality in the UK. Meta-analysis was conducted using a random-effects model. Results: Out of 309 identified articles, 10 studies reporting on 2448 hip fracture patients met the inclusion criteria. Meta-analysis showed that the estimated mortality rate in patients with laboratory confirmed COVID-19 infection was 32.5% (95% CI= 28.3 to 37.0) compared to 8.6% (95% CI= 6.3 to 11.6) in COVID-19 negative patients. Meta-analysis of 9 comparative studies showed a significantly higher mortality in patients with laboratory confirmed COVID-19 infection as compared to patients without (RR=3.937, 95% CI= 2.867 to 5.406, P<.001). Similar findings were obtained when comparing mortality in COVID-19 laboratory confirmed or clinically suspected infected vs non-infected patients (RR=4.576, 95% CI = 3.589 to 5.835, P <.001). Conclusions: COVID-19 infection is associated with a 4-fold increase in mortality risk in hip fracture patients. Every effort should be made to avoid COVID-19 infection and nosocomial exposure in this highly vulnerable patient group.

Sage, Salvia officinalis L., Constituents, Hepatoprotective Activity, and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis.

Sage, Salvia officinalis L., is used worldwide as an aromatic herb for culinary purposes as well as a traditional medicinal agent for various ailments. Current investigations exhibited the effects of extended dryings of the herb on the yields, composition, oil quality, and hepatoprotective as well as anti-cancer biological activities of the hydrodistillation-obtained essential oils from the aerial parts of the plant. The essential oils' yields, compositions, and biological activities levels of the fresh and differently timed and room-temperature dried herbs differed significantly. The lowest yields of the essential oil were obtained from the fresh herbs (FH, 631 mg, 0.16%), while the highest yield was obtained from the two-week dried herbs (2WDH, 1102 mg, 0.28%). A notable decrease in monoterpenes, with increment in the sesquiterpene constituents, was observed for the FH-based essential oil as compared to all the other batches of the essential oils obtained from the different-timed dried herbs. Additionally, characteristic chemotypic constituents of sage, i.e., α-pinene, camphene, ß-pinene, myrcene, 1, 8-cineole, α-thujone, and camphor, were present in significantly higher proportions in all the dried herbs' essential oils as compared to the FH-based essential oil. The in vivo hepatoprotective activity demonstrated significant reductions in the levels of AST, ALT, and ALP, as well as a significant increase in the total protein (p < 0.05) contents level, as compared to the acetaminophen (AAP) administered experimental group of rats. A significant reduction (p < 0.05) in the ALT level was demonstrated by the 4WDH-based essential oil in comparison to the FH-based essential oil. The levels of creatinine, cholesterol, and triglycerides were reduced (p < 0.05) in the pre-treated rats by the essential oil batches, with non-significant differences found among them as a result of the herbs dryings based oils. A notable increase in the viability of the cells, and total antioxidant capacity (TAOxC) levels, together with the reduction in malondialdehyde (MDA) levels were observed by the essential oils obtained from all the batches as compared with the AAP-treated cell-lines, HepG-2, HeLa, and MCF-7, that indicated the in vitro hepatoprotective effects of the sage essential oils. However, significant improvements in the in vivo and in vitro hepatoprotective activities with the 4WDH-based oil, as compared to all other essential oil-batches and silymarin standard demonstrated the beneficial effects of the drying protocol for the herb for its medicinal purposes.

The Anti-Inflammatory Effect of a γ-Lactone Isolated from Ostrich Oil of Struthio camelus (Ratite) and Its Formulated Nano-Emulsion in Formalin-Induced Paw Edema.

The ostrich oil of Struthio camelus (Ratite) found uses in folk medicine as an anti-inflammatory in eczema and contact dermatitis. The anti-inflammatory effect of a γ-lactone (5-hexyl-3H-furan-2-one) isolated from ostrich oil and its formulated nano-emulsion in formalin-induced paw edema was investigated in this study. Ostrich oil was saponified using a standard procedure; the aqueous residue was fractionated, purified, and characterized as γ-lactone (5-hexyl-3H-furan-2-one) through the interpretation of IR, NMR, and MS analyses. The γ-lactone was formulated as nano-emulsion using methylcellulose (MC) for oral solubilized form. The γ-lactone methylcellulose nanoparticles (γ-lactone-MC-NPs) were characterized for their size, shape, and encapsulation efficiency with a uniform size of 300 nm and 59.9% drug content. The γ-lactone was applied topically, while the formulated nanoparticles (NPs) were administered orally to rats. A non-steroidal anti-inflammatory drug (diclofenac gel) was used as a reference drug for topical use and ibuprofen suspension for oral administration. Edema was measured using the plethysmograph method. Both γ-lactone and γ-lactone-MC-NPs showed reduction of formalin-induced paw edema in rats and proved to be better than the reference drugs; diclofenac gel and ibuprofen emulsion. Histological examination of the skin tissue revealed increased skin thickness with subepidermal edema and mixed inflammatory cellular infiltration, which were significantly reduced by the γ-lactone compared to the positive control (p-value = 0.00013). Diuretic and toxicity studies of oral γ-lactone-MC-NPs were performed. No diuretic activity was observed. However, lethargy, drowsiness, and refusal to feeding observed may limit its oral administration.

COVID-19 infection is related to differences in the use of personal protective equipment by orthopaedic specialist trainees caring for hip fracture patients during the second surge of COVID-19 in the North West of England.

INTRODUCTION: Personal protective equipment (PPE) may protect health-care workers from COVID-19 infection and limit nosocomial spread to vulnerable hip fracture patients. METHODS: We performed a cross-sectional survey amongst orthopaedic trainees to explore PPE practice in 19 hospitals caring for hip fracture patients in the North West of England. RESULTS: During the second wave of the pandemic, 14/19 (74%) hospitals experienced an outbreak of COVID-19 amongst staff or patients on the orthopaedic wards. An FFP3 respirator mask was used by doctors in only 6/19 (32%) hospitals when seeing patients with COVID-19 and a cough and in 5/19 (26%) hospitals when seeing asymptomatic patients with COVID-19. A COVID-19 outbreak was reported in 11/13 (85%) orthopaedic units where staff wore fluid resistant surgical masks compared to 3/6 (50%) units using an FFP3 respirator mask (RR 1.69, 95% CI 0.74-3.89) when caring for symptomatic patients with COVID-19. Similarly, a COVID-19 outbreak was reported in more orthopaedic units caring for asymptomatic patients with COVID-19 where staff wore fluid resistant surgical masks (12/14 (86%)) as compared to an FFP3 respirator mask (2/5 (40%)) (RR 2.14, 95% CI 0.72-6.4). CONCLUSION: Urgent re-evaluation of PPE use is required to reduce nosocomial spread of COVID-19, amongst highly vulnerable patients with hip fracture.

Phytochemical Analysis, Pharmacological and Safety Evaluations of Halophytic Plant, Salsola cyclophylla.

Salsola cyclophylla, an edible halophyte, is traditionally used for inflammation and pain. To confirm the claimed anti-inflammatory and analgesic properties, a detailed study on respective pharmacological actions was undertaken. The activities are contemplated to arise from its phytoconstituents. The LC-MS analysis of S. cyclophylla 95% aqueous-ethanolic extract revealed the presence of 52 compounds belonging to phenols, flavonoids, coumarins, and aliphatics class. A high concentration of Mn, Fe, and Zn was detected by atomic absorption spectroscopic analysis. The ethyl acetate extract showed the highest flavonoid contents (5.94 ± 0.04 mg/g, Quercetin Equivalents) and Fe2+-chelation (52%) potential with DPPH radicals-quenching IC50 at 1.35 ± 0.16 mg/mL, while the aqueous ethanolic extract exhibited maximum phenolics contents (136.08 ± 0.12 mg/g, gallic acid equivalents) with DPPH scavenging potential at IC50 0.615 ± 0.06 mg/mL. Aqueous ethanolic extract and standard quercetin DPPH radicals scavenging's were equal potent at 10 mg/mL concentrations. The aqueous ethanolic extract showed highest analgesic effect with pain reduction rates 89.86% (p = 0.03), 87.50% (p < 0.01), and 99.66% (p = 0.0004) after 60, 90, and 120 min, respectively. Additionally, aqueous ethanolic extract exhibited the highest anti-inflammation capacity at 41.07% (p < 0.0001), 34.51% (p < 0.0001), and 24.82% (p < 0.0001) after 2, 3, and 6 h of extract's administration, respectively. The phytochemical constituents, significant anti-oxidant potential, remarkable analgesic, and anti-inflammatory bioactivities of extracts supported the traditionally claimed anti-inflammatory and analgesic plant activities.

Hartmann's Pouch Stones and Laparoscopic Cholecystectomy: The Challenges and the Solutions.

BACKGROUND & OBJECTIVE: Hartmann's pouch stones (HPS) encountered during laparoscopic cholecystectomy (LC) may hinder safe dissection of the cystic pedicle or be complicated by mucocele, empyema, or Mirizzi syndrome; distorting the anatomy and increasing the risk of bile duct injury. We studied the incidence, presentations, operative challenges, and outcomes of HPS. METHODS: A cohort study of a prospectively maintained database of LCs and bile duct explorations performed by a single surgeon. Patients were divided into two groups: those with HPS and those without. Patients' demographics, clinical presentation, intra-operative findings, and postoperative outcomes were compared. RESULTS: Of the 5136 patients, 612 (11.9%) had HPS. The HPS group were more likely to present with acute cholecystitis (27.9% vs 5.9%, P = .000) and more patients underwent emergency LC (50.7% vs 41.5%, P = .000). The HPS group had more difficult cholecystectomies, with 46.1% vs 11.8% in the non-HPS group being operative difficulty grade 4 and 5. Mucocele, empyema, and Mirizzi syndrome were more common in the HPS group (24.0% vs 3.7% P = .000, 30.9% vs 3.7% P = .000, 1.8% vs 0.9% P = .000, respectively). There was no significant difference in the open conversion rate or complications. CONCLUSION: HPS increase the difficulty of LC. Surgeons should be aware of their presence and should employ appropriate dissection strategies. Sharp or diathermy dissection should be avoided. Dislodging the stone into the gall bladder, stone removal, swab dissection, and cholangiography are useful measures to avoid ductal injury and reduce the conversion rate.

Operational framework and training standard requirements for AI-empowered robotic surgery.

BACKGROUND: For autonomous robot-delivered surgeries to ever become a feasible option, we recommend the combination of human-centered artificial intelligence (AI) and transparent machine learning (ML), with integrated Gross anatomy models. This can be supplemented with medical imaging data of cadavers for performance evaluation. METHODS: We reviewed technological advances and state-of-the-art documented developments. We undertook a literature search on surgical robotics and skills, tracing agent studies, relevant frameworks, and standards for AI. This embraced transparency aspects of AI. CONCLUSION: We recommend "a procedure/skill template" for teaching AI that can be used by a surgeon. Similar existing methodologies show that when such a metric-based approach is used for training surgeons, cardiologists, and anesthetists, it results in a >40% error reduction in objectively assessed intraoperative procedures. The integration of Explainable AI and ML, and novel tissue characterization sensorics to tele-operated robotic-assisted procedures with medical imaged cadavers, provides robotic guidance and refines tissue classifications at a molecular level.

Developments in Transduction, Connectivity and AI/Machine Learning for Point-of-Care Testing.

We review some emerging trends in transduction, connectivity and data analytics for Point-of-Care Testing (POCT) of infectious and non-communicable diseases. The patient need for POCT is described along with developments in portable diagnostics, specifically in respect of Lab-on-chip and microfluidic systems. We describe some novel electrochemical and photonic systems and the use of mobile phones in terms of hardware components and device connectivity for POCT. Developments in data analytics that are applicable for POCT are described with an overview of data structures and recent AI/Machine learning trends. The most important methodologies of machine learning, including deep learning methods, are summarised. The potential value of trends within POCT systems for clinical diagnostics within Lower Middle Income Countries (LMICs) and the Least Developed Countries (LDCs) are highlighted.

The role of artificial intelligence and machine learning in harmonization of high-resolution post-mortem MRI (virtopsy) with respect to brain microstructure.

Enhanced resolution of 7 T magnetic resonance imaging (MRI) scanners has considerably advanced our knowledge of structure and function in human and animal brains. Post-industrialized countries are particularly prone to an ever-increasing number of ageing individuals and ageing-associated neurodegenerative diseases. Neurodegenerative diseases are associated with volume loss in the affected brain. MRI diagnoses and monitoring of subtle volume changes in the ageing/diseased brains have the potential to become standard diagnostic tools. Even with the superior resolution of 7 T MRI scanners, the microstructural changes comprising cell types, cell numbers, and cellular processes, are still undetectable. Knowledge of origin, nature, and progression for microstructural changes are necessary to understand pathogenetic stages in the relentless neurodegenerative diseases, as well as to develop therapeutic tools that delay or stop neurodegenerative processes at their earliest stage. We illustrate the gap in resolution by comparing the identical regions of the post-mortem in situ 7 T MR images (virtual autopsy or virtopsy) with the histological observations in serial sections through the same brain. We also described the protocols and limitations associated with these comparisons, as well as the necessity of supercomputers and data management for "Big data". Analysis of neuron and/or glial number by using a body of mathematical tools and guidelines (stereology) is time-consuming, cumbersome, and still restricted to trained human investigators. Development of tools based on machine learning (ML) and artificial intelligence (AI) could considerably accelerate studies on localization, onset, and progression of neuron loss. Finally, these observations could disentangle the mechanisms of volume loss into stages of reversible atrophy and/or irreversible fatal cell death. This AI- and ML-based cooperation between virtopsy and histology could bridge the present gap between virtual reality and neuropathology. It could also culminate in the creation of an imaging-associated comprehensive database. This database would include genetic, clinical, epidemiological, and technical aspects that could help to alleviate or even stop the adverse effects of neurodegenerative diseases on affected individuals, their families, and society.

Legal, regulatory, and ethical frameworks for development of standards in artificial intelligence (AI) and autonomous robotic surgery.

BACKGROUND: This paper aims to move the debate forward regarding the potential for artificial intelligence (AI) and autonomous robotic surgery with a particular focus on ethics, regulation and legal aspects (such as civil law, international law, tort law, liability, medical malpractice, privacy and product/device legislation, among other aspects). METHODS: We conducted an intensive literature search on current or emerging AI and autonomous technologies (eg, vehicles), military and medical technologies (eg, surgical robots), relevant frameworks and standards, cyber security/safety- and legal-systems worldwide. We provide a discussion on unique challenges for robotic surgery faced by proposals made for AI more generally (eg, Explainable AI) and machine learning more specifically (eg, black box), as well as recommendations for developing and improving relevant frameworks or standards. CONCLUSION: We classify responsibility into the following: (1) Accountability; (2) Liability; and (3) Culpability. All three aspects were addressed when discussing responsibility for AI and autonomous surgical robots, be these civil or military patients (however, these aspects may require revision in cases where robots become citizens). The component which produces the least clarity is Culpability, since it is unthinkable in the current state of technology. We envision that in the near future a surgical robot can learn and perform routine operative tasks that can then be supervised by a human surgeon. This represents a surgical parallel to autonomously driven vehicles. Here a human remains in the 'driving seat' as a 'doctor-in-the-loop' thereby safeguarding patients undergoing operations that are supported by surgical machines with autonomous capabilities.

Diagnostic laparoscopy to investigate unexplained lactic acidosis in critically ill patients - A descriptive single centre cohort study.

INTRODUCTION: Unexplained lactic acidosis (LA) in a critically ill patient often prompts investigations to rule out any reversible intra-abdominal cause. Equivocal results can lead to an emergency laparotomy (EL) with subsequent high morbidity and mortality rates. Our objective was to determine the clinical impact of urgent diagnostic laparoscopy (UDL) in such patients. METHODS: This was a descriptive single-centre cohort study. UDL on 28 consecutive critically ill patients with unexplained LA who were referred to a single surgeon over 16 years period were analysed. UDL was proformed either at bedside or in theatre without prior computerised tomography (CT) scan. Patient's demographics, ASA grade, referral route and intraoperative findings were analysed. RESULTS: Eighteen patients underwent bedside UDL in the critical care setting and further 10 had UDL in theatre. Fourteen patients had normal UDL, out of these 10 had LA secondary to low cardiac output states. Fourteen patients had positive UDL findings. Seven patients had features of mesenteric ischaemia, two had gangrenous gallbladder, two had hepatic ischaemia, one patient had acute pancreatitis, one had gangrenous uterus and one had gastric volvulus. Five of the 14 patients with positive UDL were converted to laparotomy for definitive management. In total, of the 28 patients in the cohort, 23 patients avoided EL. CONCLUSION: UDL is useful and feasible investigation for unexplained LA in the critically ill patients and it can avoid unnecessary EL in many patients. We would recommend the use of UDL as a safe and feasible investigation in such patients.

Hijama therapy (wet cupping) - its potential use to complement British healthcare in practice, understanding, evidence and regulation.

Wet cupping was used in the nineteenth century for treatment of patients in the United Kingdom (UK) by a few experienced practitioners. Revival Hijama use by practitioners in the UK in recent years has been observed as well as interest from the public, with developments of specific certified training programmes, established businesses providing tailored Hijama therapy Clinical Waste disposal services, provisions of insurance cover, involvement of medical professionals and membership with the General Regulatory Council for Complementary Therapies (GRCCT). However, there has also been noted that there is not much in the way of guidance or regulation. Therefore, we would like to initiate some communication and understanding of Hijama (wet cupping) to benefit medical professionals, discussing recent research undertaken as a basis for potentially more in the future (evidence-based practice), in the likely event that a patient might request to be referred for this therapy during a consultation.

Autopsy in Islam: Considerations for Deceased Muslims and Their Families Currently and in the Future.

Religious beliefs and cultures have influenced treatment of dead bodies in different ways by nations throughout history, and attitudes toward the deceased individuals have changed across time and so has the role and mechanism of autopsy. Islam has been a part of Europe for a long time; therefore, we would like to emphasize the important issues for Muslims and their families regarding death, autopsy, and funeral and to describe international perspectives of Muslim autopsies. Muslims have expressed their views on autopsy publically and internationally, and there have been claims of violation of the deceased, delays in burial, and nonconsideration of their religious beliefs. In this article, we aim to increase awareness and understanding of doctors about the religious and ethical issues important to Muslims and their families, so that appropriate considerations may be made where possible with regard to respectful treatment of deceased loved ones to decrease tensions presently being faced. Forensic medicine doctors could assist by undertaking autopsy without delay, in a private room by those of the same sex, and covering parts of the body not being worked on at that time.

Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance.

Most studies on malaria-parasite digestion of hemoglobin (Hb) have been performed using P. falciparum maintained in mature erythrocytes, in vitro. In this study, we examine Plasmodium Hb degradation in vivo in mice, using the parasite P. berghei, and show that it is possible to create mutant parasites lacking enzymes involved in the initial steps of Hb proteolysis. These mutants only complete development in reticulocytes and mature into both schizonts and gametocytes. Hb degradation is severely impaired and large amounts of undigested Hb remains in the reticulocyte cytoplasm and in vesicles in the parasite. The mutants produce little or no hemozoin (Hz), the detoxification by-product of Hb degradation. Further, they are resistant to chloroquine, an antimalarial drug that interferes with Hz formation, but their sensitivity to artesunate, also thought to be dependent on Hb degradation, is retained. Survival in reticulocytes with reduced or absent Hb digestion may imply a novel mechanism of drug resistance. These findings have implications for drug development against human-malaria parasites, such as P. vivax and P. ovale, which develop inside reticulocytes.

A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites.

A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. In this study, we present data on safety and protective efficacy using sporozoites with deletions of two genes, that is the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, PbΔb9ΔslarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high-level protection. The human PfΔb9ΔslarpGAP generated without drug resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a PfΔb9ΔslarpSPZ vaccine.