Notes

Lighting adaptation qualities of melanopsin.
Open extremity fractures can be life-changing events. Clinical guidelines on the management of these injuries aim to standardise the care of patients by presenting evidence-based recommendations. We performed a scoping systematic review to identify all national clinical practice guidelines published to date.

A PRISMA-compliant scoping systematic review was designed to identify all national or federal guidelines for the management of open fractures, with no limitations for language or publication date. WP1066 EMBASE and MEDLINE database were searched. Article screening and full-text review was performed in a blinded fashion in parallel by two authors.

Following elimination of duplicates, 376 individual publications were identified and reviewed. In total, 12 clinical guidelines were identified, authored by groups in the UK, USA, the Netherlands, Finland, and Malawi. Two of these focused exclusively on antibiotic prophylaxis and one on combat-related injuries, with the remaining nine presented wide-scope recommen collaboration may be an alternative for adapting guidelines to match local resources and healthcare systems for use across national borders.Prion protein (PrP) aggregation and formation of PrP amyloid (APrP) are central events in the pathogenesis of prion diseases. In the dominantly inherited prion protein amyloidosis known as Gerstmann-Sträussler-Scheinker (GSS) disease, plaques made of PrP amyloid are present throughout the brain. The c.593t > c mutation in the prion protein gene (PRNP) results in a phenylalanine to serine amino acid substitution at PrP residue 198 (F198S) and causes the most severe amyloidosis among GSS variants. It has been shown that neurodegeneration in this disease is associated with the presence of extracellular APrP plaques and neuronal intracytoplasmic Tau inclusions, that have been shown to contain paired helical filaments identical to those found in Alzheimer disease. Using cryogenic electron microscopy (cryo-EM), we determined for the first time the structures of filaments of human APrP, isolated post-mortem from the brain of two symptomatic PRNP F198S mutation carriers. We report that in GSS (F198S) APrP filaments are composed of dimeric, trimeric and tetrameric left-handed protofilaments with their protomers sharing a common protein fold. The protomers in the cross-β spines consist of 62 amino acids and span from glycine 80 to phenylalanine 141, adopting a previously unseen spiral fold with a thicker outer layer and a thinner inner layer. Each protomer comprises nine short β-strands, with the β1 and β8 strands, as well as the β4 and β9 strands, forming a steric zipper. The data obtained by cryo-EM provide insights into the structural complexity of the PrP filament in a dominantly inherited human PrP amyloidosis. The novel findings highlight the urgency of extending our knowledge of the filaments' structures that may underlie distinct clinical and pathologic phenotypes of human neurodegenerative diseases.The first section of the bone marrow workshop of the European Association of Haematopathology (EAHP) 2020 Virtual Meeting was dedicated to pediatric myeloid neoplasms. The section covered the whole spectrum of myeloid neoplasms, including myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), and acute myeloid leukemia (AML). The workshop cases are hereby presented, preceded by an introduction on these overall rare diseases in this age group. Very rare entities such as primary myelofibrosis, pediatric MDS with fibrosis, and MDS/MPN with JMML-like features and t(4;17)(q12;q21); FIP1L1RARA fusion, are described in more detail.
Total knee arthroplasty (TKA) in major deformities with ligament insufficiency may require a higher constraint, with bone sacrifice and concerns about long-term survivorship. Mid-level constraint liners have been recently introduced, but few studies described their outcomes. The aim of this study is to evaluate the short to mid-term outcomes of a constrained postero-stabilized (CPS) insert for primary TKA in moderate to severe deformities.

All patients who underwent TKA using a CPS liner in two centers between 2015 and 2017 were included in the study. The indications were (1) valgus deformity type 2-3 partially correctable; (2) severe varus deformity with varus thrust; (3) post-traumatic deformity with major ligamentous insufficiency and any case of intra-operative ligament insufficiency. Patients were evaluated according to the Knee Society Scoring System (KSS), the Hospital for Special Surgeryscore (HSS), the Western Ontario and Mc Master University (WOMAC) and the Oxford Knee score (OKS). X-rays were evaluated according to the Knee Society Roentgenographic Evaluation System.

Forty-seven TKA were included, with an average age of 66.1 ± 10.3years and an average follow-up of 68.4 ± 6months. All patients demonstrated a moderate to severe pre-operative mediolateral instability. All the scores significantly improved (p < 0.0001). In 71.4% of cases, the outcomes were excellent or very good. There were no failures due to aseptic loosening but one failure due to a traumatic ligament rupture. The cumulative survivorship was 97.9% ± 2.1% at 84months.

This mid-range constraint total knee replacement demonstrated promising outcomes and survival at mid-term follow-up.

IV (case series).
IV (case series).
The clinical effectiveness of robotic arm-assisted systems remains unclear for total hip arthroplasty (THA) in patients suffering from osteoarthritis secondary to developmental dysplasia of the hip (DDH).

Patients with DDH who underwent primary THA were included in this study. We conducted a propensity score-matched comparison between THAs using a robotic arm-assisted system (Mako group) versus those using the manual procedure (manual group) to compare the absolute differences in cup placement angles measured using postoperative computed tomography and those planned preoperatively.

A total of 217 patients with osteoarthritis due to DDH met the inclusion criteria. Eighty-four patients were matched as the Mako group and 84 as the manual group. The differences were smaller in the Mako group than the manual group in terms of both inclination and anteversion angles (1.1 ± 1.0 versus 4.2 ± 3.1, respectively; 95% CI, 2.4 to 3.8; p < 0.0001, and 1.2 ± 1.1 versus 5.8 ± 4.0, respectively; 95% CI, 3.7 to 5.5; p < 0.0001).

The robotic arm-assisted system may provide more accurate cup placement in THA for DDH.
The robotic arm-assisted system may provide more accurate cup placement in THA for DDH.Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae), commonly known as Sarpagandha or Indian snakeroot, has long been used in the traditional treatment of snakebites, hypertension, and mental illness. The plant is known to produce an array of indole alkaloids such as reserpine, ajmaline, amalicine, etc. which show immense pharmacological and biomedical significance. However, owing to its poor seed viability, lesser germination rate and overexploitation for several decades for its commercially important bioactive constituents, the plant has become endangered in its natural habitat. The present review comprehensively encompasses the various biotechnological tools employed in this endangered Ayurvedic plant for its in vitro propagation, role of plant growth regulators and additives in direct and indirect regeneration, somatic embryogenesis and synthetic seed production, secondary metabolite production in vitro, and assessment of clonal fidelity using molecular markers and genetic transformation. In addition, elicitation and other methods of optimization of its indole-alkaloids are also described herewith. KEY POINTS • Latest literature on in vitro propagation of Rauvolfia serpentina • Biotechnological production and optimization of indole alkaloids • Clonal fidelity and transgenic studies in R. serpentina.The influences of three wheat gluten peptides (WGP-LL, WGP-LML, and WGP-LLL) on the osmotic stress tolerance and membrane lipid component in brewer's yeast were investigated. The results demonstrated that the growth and survival of yeast under osmotic stress were enhanced by WGP supplementation. The addition of WGP upregulated the expressions of OLE1 (encoded the delta-9 fatty acid desaturase) and ERG1 (encoded squalene epoxidase) genes under osmotic stress. At the same time, WGP addition enhanced palmitoleic acid (C161) content, unsaturated fatty acids/saturated fatty acids ratio, and the amount of ergosterol in yeast cells under osmotic stress. Furthermore, yeast cells in WGP-LL and WGP-LLL groups were more resistant to osmotic stress. WGP-LL and WGP-LLL addition caused 25.08% and 27.02% increase in membrane fluidity, 22.36% and 29.54% reduction in membrane permeability, 18.38% and 14.26% rise in membrane integrity in yeast cells, respectively. In addition, scanning electron microscopy analysis revealed that the addition of WGP was capable of maintaining yeast cell morphology and reducing cell membrane damage under osmotic stress. Thus, alteration of membrane lipid component by WGP was an effective approach for increasing the growth and survival of yeast cells under osmotic stress. KEY POINTS •WGP addition enhanced cell growth and survival of yeast under osmotic stress. •WGP addition increased unsaturated fatty acids and ergosterol contents in yeast. •WGP supplementation improved membrane homeostasis in yeast at osmotic stress.Recent years have seen an increased focus on the advancement of naturally derived products for the treatment of cancer. Since the beginning of recorded history, nature has provided a variety of medicinal agents, and an overwhelming number of drugs that we have today are derived from natural sources. Such natural agents are prominently used to treat several diseases such as diabetes, malaria, Alzheimer's, pulmonary disorders, etc. with cancer being the highlight of this review. Due to the rapid development of resistance to chemotherapeutic drugs, the hunt for effective novel drugs is still a paramount concern in cancer treatment. Moreover, many chemotherapy drugs typically have high toxicity and adverse side effects, which necessitates the need to develop anti-tumor drugs that can be employed to treat deadly tumors with fewer negative effects on health and better efficacy. Isolation of several chemotherapeutic drugs has been conducted from a wide range of natural sources which include plants, microbes, fungi, obe-derived anticancer agents target various sarcomas, carcinomas, and lymphomas.The clinical information on the relationship between the cardiac contact distance (CCD), the maximum dose (Dmax) delivered to the left anterior descending (LAD) coronary artery and the mean heart dose has mostly focused on patients with breast-conserving surgery (BCS), being scarce in postmastectomy patients. The aim of this study is to determine the association between the CCD and the Dmax delivered to the LAD. The secondary objective was to evaluate the dosimetric results of comparing three-dimensional conformal radiotherapy (3D-CRT) to intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques for post mastectomized breast cancer patients with irradiation to the left chest wall. 53 cases of women who received adjuvant standard fractionated postmastectomy radiotherapy (PMRT) were used. Three types of plans were created for each patient 3D-CRT, seven equidistant IMRT fields, and four partial VMAT arcs. Correlations were evaluated using Pearson's correlation coefficient. Plans made with IMRT and VMAT showed improved homogeneity and conformity.
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