Complete Loss Research Articles

Malignant peripheral nerve sheath tumor: a clinicopathological analysis

Objective: To investigate the clinicopathological, immunophenotypic, and genetic features of malignant peripheral nerve sheath tumor (MPNST). Methods: Twenty-three cases of MPNST were diagnosed at the Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University), China, between January 2012 and December 2022 and thus included in the study. EnVision immunostaining and next-generation sequencing (NGS) were used to examine their immunophenotypical characteristics and genomic aberrations, respectively. Results: There were 10 males and 13 females, with an age range of 11 to 79 years (median 36 years), including 14 cases of neurofibromatosis type I-associated MPNST and 9 cases of sporadic MPNST. The tumors were located in extremities (7 cases), trunk (4 cases), neck and shoulder (3 cases), chest cavity (3 cases), paraspinal area (2 cases), abdominal cavity (2 cases), retroperitoneum (1 case), and pelvic cavity (1 case). Morphologically, the tumors were composed of dense spindle cells arranged in fascicles. Periphery neurofibroma-like pattern was found in 73.9% (17/23) of the cases. Under low magnification, alternating hypercellular and hypocellular areas resembled marbled appearance. Under high power, the tumor cell nuclei were irregular, presenting with oval, conical, comma-like, bullet-like or wavy contour. In 7 cases, the tumor cells demonstrated marked cytological pleomorphism and rare giant tumor cells. The mitotic figures were commonly not less than 3/10 HPF, and geographic necrosis was often noted. Immunohistochemically, tumor cells were positive for S-100 (14/23, 60.9%) and SOX10 (11/23, 47.8%). The loss of the CD34-positive fibroblastic network encountered in neurofibromas was observed in 14/17 of the MPNST cases. The loss of H3K27me3 expression was observed in 82.6% (19/23) of the cases. Moreover, SDHA and SDHB losses were presented in one case. NGS revealed that NF1 gene loss of function (germline or somatic) were found in all 5 cases tested. Furthermore, four cases accompanied with somatic mutations of SUZ12 gene and half of them had somatic mutations of TP53 gene, while one case with germline mutation in SDHA gene and somatic mutations in FAT1, BRAF, and KRAS genes. Available clinical follow-up was obtained in 19 cases and ranged from 1 to 67 months. Four patients died of the disease, all of whom had the clinical history of neurofibromatosis type Ⅰ. Conclusions: MPNST is difficult to be differentiated from a variety of spindle cell tumors due to its wide spectrum of histological morphology and complex genetic changes. H3K27me3 is a useful diagnostic marker, while the loss of CD34 positive fibroblastic network can also be a diagnostic feature of MPNST. NF1 gene inactivation mutations and complete loss of PRC2 activity are the common molecular diagnostic features, but other less commonly recurred genomic aberrations might also contribute to the MPNST pathogenesis.

Small-interfering RNA targeting proprotein convertase subtilisin/kexin type 9 might promote fatty liver disease and hepatocellular carcinoma through upregulation of CD36.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptor and fatty acid translocase CD36, inducing lysosomal degradation of these two receptors in the liver cells. Both monoclonal antibody (mAb) and small-interfering RNA (siRNA) targeting PCSK9 have been designed for treatment of familial hypercholesterolemia recently, with elevating LDL receptors on the liver cell surface and increasing LDL uptake as the main beneficial mechanism. However, given that the binding domains of PCSK9 for LDL receptor and CD36 are different, and PCSK9 mAb only attacks the domain for LDL receptor, CD36 expression remains partially controlled under PCSK9 mAb treatment. In contrast, PCSK9 siRNA brings on complete loss of PCSK9, resulting in overexpression of CD36. Based on the fact that CD36 is a key factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and subsequent hepatocellular carcinoma (HCC), the risk of developing NAFLD and HCC on long-term use of PCSK9 siRNA is thus raised as a hypothesis. Additionally, because CD36 is also involved in the promotion of malignant diseases other than HCC, such as acute myeloid leukemia, gastric cancer, breast cancer, and colorectal cancer, the speculative danger of flourishing these malignancies by PCSK9 siRNA is discussed as well.

Grainyhead-like 2 is required for morphological integrity of mouse embryonic stem cells and orderly formation of inner ear-like organoids.

Mutations in the transcription factor gene grainyhead-like 2 (GRHL2) are associated with progressive non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28) in humans. Since complete loss of Grhl2 is lethal in mouse embryos, we studied its role during inner ear pathology and hearing loss in vitro. To this end, we generated different homozygous deletions to knockout Grhl2 in mouse embryonic stem cells (Grhl2-KO ESCs), including some mimicking naturally occurring truncations in the dimerisation domain related to human DFNA28. Under naïve culture conditions, Grhl2-KO cells in suspension were more heterogenous in size and larger than wild-type controls. Adherent Grhl2-KO cells were also larger, with a less uniform shape, flattened, less circular morphology, forming loose monolayer colonies with poorly defined edges. These changes correlated with lower expression of epithelial cadherin Cdh1 but no changes in tight junction markers (Ocln, Tjp2) or other Grhl isoforms (Grhl1, Grhl3). Clonogenicity from single cells, proliferation rates of cell populations and proliferation markers were reduced in Grhl2-KO ESCs. We next induced stepwise directed differentiation of Grhl2-KO ESCs along an otic pathway, giving rise to three-dimensional inner ear-like organoids (IELOs). Quantitative morphometry revealed that Grhl2-KO cells initially formed larger IELOs with a less compacted structure, more eccentric shape and increased surface area. These morphological changes persisted for up to oneweek. They were partially rescued by forced cell aggregation and fully restored by stably overexpressing exogenous Grhl2 in Grhl2-KO ESCs, indicating that Grhl2 alters cell-cell interactions. On day 8, aggregates were transferred into minimal maturation medium to allow self-guided organogenesis for another two weeks. During this period, Grhl2-KO cells and wild-type controls developed similarly, expressing neural, neuronal and sensory hair cell markers, while maintaining their initial differences in size and shape. In summary, Grhl2 is required for morphological maintenance of ESCs and orderly formation of IELOs, consistent with an essential role in organising epithelial integrity during inner ear development. Our findings validate quantitative morphometry as a useful, non-invasive screening method for molecular phenotyping of candidate mutations during organoid development.

Socio-demographic factors associated with COVID-19 vaccine uptake and refusal among Ugandan women

BackgroundThis paper analyzes associations of socio-demographic factors with the uptake of COVID-19 vaccines, the refusal to get vaccinated against COVID-19, and various reasons stated for refusing vaccination against COVID-19 among a representative sample of Ugandan women.MethodsThis paper utilizes a representative cross-sectional survey collected among women aged 15-49 years in Uganda between September and November 2021. Regression analyses are used to study the associations of a broad range of socio-demographic characteristics with COVID-19 vaccine uptake, refusal of vaccination, and reasons for refusal among the respondents.Results4211 women were included in the analysis. 11% of them were vaccinated against COVID-19, 76% were willing to get vaccinated, 13% were unwilling to get vaccinated. Fear of side effects was the most commonly stated reason for refusing vaccination (69%). Factors significantly and positively associated with being vaccinated against COVID-19 were age, higher education, urban residency, having savings, partial instead of complete income loss during the pandemic, and usage of modern contraceptives. Factors significantly and positively associated with refusing vaccination against COVID-19 were urban residency and current pregnancy, while age, having savings, and using modern contraceptives were factors associated with a lower likelihood of refusing vaccination, albeit with varying statistical significance. Few factors were strongly related to the stated reasons for refusing the vaccines; the fear of side effects significantly increased with age, while having received negative information on the vaccines was significantly less common among women with higher education.ConclusionsThis study documents a low COVID-19 vaccination rate and a high willingness to get vaccinated among Ugandan women. Positive age and education gradients in vaccine uptake point to inequity in access to vaccination, potentially resulting from prioritizations of groups at particularly high risk. Refusal to be vaccinated was relatively low and systematic factors behind vaccine refusal were hardly to be found, even less so for particular reasons given for refusal.

Assessment of the behavior of spent nuclear fuel in Ukraine

Abstract. Before June 2023 the Zaporizhzhya Nuclear Power Plant, which is the largest nuclear facility in Europe, had suffered a complete loss of external power seven times since the beginning of the Russian invasion. This forced it to rely on emergency diesel generators to guarantee the safety and security functions of the plant, such as reactor cooling. From that, it appears of meaningful importance to evaluate the performance of all its nuclear facilities, among which the building where the spent fuel storage pool (SFP) is located, to assess what consequences anomalous/abnormal or accident events may determine. Contrary to dry storage, the dry cask/packaging system is stored on open concrete pads within a protected area of the plant site; the wet storage requires a hydraulic environment such as the water pools where SF is safely stored. The hydraulic effluent and the physical containment barriers act as confinement and shielding, guaranteeing safety criteria are fulfilled. In this preliminary study, the attention is thus paid to the SFP; for this reason, a description of its behavior and filling status must be provided. Since 2001, spent nuclear fuel (SNF) from 6 VVER (water–water energy reactor)-1000 units has been stored in the dry storage facility at the Zaporizhzhya Nuclear Power Plant. This means that, despite radioactive decay, the total activity of such inventory may exceed 30 times that of the fourth damaged Chornobyl unit at the time of the accident, and this is due to long-lived actinides (2 × 1019 Bq), 137Cs (1 × 1019 Bq) and 90Sr (9 × 1018 Bq). Continued damage caused by a missile attack on the SFP (e.g., cyclic, dynamic, and thermal loadings) may increase the risk of loss of integrity, because, as it is widely known, concrete has low resistance under tension. In this assessment, an evaluation, therefore, the radiological risk is addressed. For such an evaluation, it is considered that an SFP in VVER-1000 is designed to store 687 fuel assemblies and 670 in VVER-440. When it is half full, which is the case for 15 Ukrainian units, it will store about 2200 t U, containing up to 1 × 1019 Bq of 137Cs, 7 × 1018 Bq of 90Sr and 1 × 1019 Bq of TUE. Moreover, if it is considered that the spent fuel pool represented the Achilles' heel of the nuclear power plant during the 2011 Fukushima accident, it appears quite obvious that there is a need to evaluate the threat associated with the SF storage condition in order to prevent the occurrence of a new severe accident or other challenging situations that the armed conflict has created and may create. The results of the analysis of the Zaporizhzhya Nuclear Power Plant behavior suggest firstly that the plant was/is subjected to high stresses its structures may not withstand for a long time. Secondly, damages may impact SFP instrumentation, which is used for monitoring, for example, radiation or hydrogen formation, leading to loss of control of the SFP facility. Further, it is shown that to prevent the global nuclear threat, nuclear safety and security systems must be maintained and upgraded with at least the introduction of new technical and environmental devices.

Experimental and numerical simulation of pull-out response in textile-reinforced concrete

Textile-reinforced concrete (TRC) is a construction material that uses continuous fibres such as carbon to create a lightweight and durable structural system. Even though TRC possesses vast possibilities in terms of its usage, identification of bond-slip behaviour at the material interface is one of the limitations that need to be addressed. Based on the literature, there are difficulties in determining the bond-slip relationship both experimentally and numerically, creating inconsistency in the results. This study aims to determine the bond-slip relation of TRC through pullout tests and validated through finite element analysis to replicate the actual bond-slip behaviour at the interface. The bond characteristics of TRC were assessed using a double-sided pullout test setup with different bond lengths of textile, namely 20 mm, 30 mm, 40 mm, 50 mm, and 60 mm. It was noticed that in short bond specimens (20 mm, 30 mm, and 40 mm), the phenomena of pullout failure were due to weakened bond at the interface until pre-peak, followed by complete loss of adhesive bond due to debonding of fibre. However, for the specimens with longer bond lengths (50 mm and 60 mm), rupture of the textile leading to a sudden loss of bond capacity was observed. Additionally, the general fibre pullout phenomenon curve was used to explain the debonding process. Using a calibrated tri-linear bond-slip interface relation, the numerical model was developed to simulate the pull-out response of fibre. The numerical model was able to reproduce experimental results, including maximum load, post-peak behaviour, and interfacial slip. The difference of maximum shear stress between pull-out tests and numerical modelling was within 2 % while the slip difference was between 4 and 31 % for different bond lengths. However, for longer bond lengths, the fibre failure mode was due to pullout instead of rupture, unlike the experimental results.

How Free Swimming Fosters the Locomotion of a Purely Oscillating Fish-like Body.

The recoil motions in free swimming, given by lateral and angular rigid motions due to the interaction with the surrounding water, are of great importance for a correct evaluation of both the forward locomotion speed and efficiency of a fish-like body. Their contribution is essential for calculating the actual movements of the body rear end whose prominent influence on the generation of the proper body deformation was established a long time ago. In particular, the recoil motions are found here to promote a dramatic improvement of the performance when damaged fishes, namely for a partial functionality of the tail or even for its complete loss, are considered. In fact, the body deformation, which turns out to become oscillating and symmetric in the extreme case, is shown to recover in the water frame a kind of undulation leading to a certain locomotion speed though at the expense of a large energy consumption. There has been a deep interest in the subject since the infancy of swimming studies, and a revival has recently arisen for biomimetic applications to robotic fish-like bodies. We intend here to apply a theoretical impulse model to the oscillating fish in free swimming as a suitable test case to strengthen our belief in the beneficial effects of the recoil motions. At the same time, we intend to exploit the linearity of the model to detect from the numerical simulations the intrinsic physical reasons related to added mass and vorticity release behind the experimental observations.

Effect of elevated temperature on mechanical properties of normal strength concrete: An overview

Concrete is frequently used in construction owing to its advantageous mechanical characteristics, including its high compressive strength, durability, workability, and fire resistance. Nevertheless, sustained exposure to fire can result in these qualities deteriorating, which poses a serious risk to concrete buildings. As a result, it is critical that researchers investigate how exposure to fire affects the mechanical characteristics of concrete in order to address this problem. Temperature, environmental conditions, the composition of the concrete mixture, and other factors all have an impact on the thermal and mechanical characteristics of concrete. This work seeks to give an overview of how exposure to fire affects the mechanical characteristics of concrete and to highlight areas that require further research. According to the study, there are three main stages that normal concrete strength goes through. The first stage sees a slight increase in strength between 20 and 300°Celsius, followed by a sharp decrease between 300 and 800°Celsius, and finally a complete loss of strength above 800°. Moreover, the fire response of concrete is strongly influenced by factors including the kind of aggregate, moisture content, concrete grade, additives, heating rate, and heating time. By making optimal use of admixtures, the fire behavior can be significantly improved.

Bidirectional multiciliated cell extrusion is controlled by Notch driven basal extrusion and Piezo1 driven apical extrusion.

Xenopus embryos are covered with a complex epithelium containing numerous multiciliated cells (MCCs). During late-stage development there is a dramatic remodeling of the epithelium that involves the complete loss of MCCs. Cell extrusion is a well-characterized process for driving cell loss while maintaining epithelial barrier function. Normal cell extrusion is typically unidirectional whereas bidirectional extrusion is often associated with disease (e.g. cancer). We describe two distinct mechanisms for MCC extrusion, a basal extrusion driven by Notch signaling and an apical extrusion driven by Piezo1. Early in the process there is a strong bias towards basal extrusion, but as development continues there is a shift towards apical extrusion. Importantly, response to the Notch signal is age-dependent and governed by the maintenance of the MCC transcriptional program such that extension of this program is protective against cell loss. In contrast, later apical extrusion is regulated by Piezo1 such that premature activation of Piezo1 leads to early extrusion while blocking Piezo1 leads to MCC maintenance. Distinct mechanisms for MCC loss underlie the importance of their removal during epithelial remodeling.

Rate, Water Pressure, and Temperature Effects in Landslide Shear Zones

AbstractThe behavior of slow‐moving landslides is controlled by the residual strength of the shear zone. Despite their mobile state, such slides can often withstand extreme events such as heavy rainfalls and earthquakes. A rate‐hardening in the shear zone is suspected to be one of the main stabilizing factors and has been well investigated, in particular for clayey soils. Soils from steep alpine landslides, on the other hand, are often dominated by silts and sands with various clay contents, and while understanding of their rate dependency is less advanced, it remains critical for the reliable risk assessment. In this article, an improved ring shear apparatus is presented and applied to investigate the rate, pore water pressure, and temperature effects in landslide shear zones. The testing program on samples from two alpine landslides in Switzerland revealed a moderately positive rate effect explaining their mobile state. An achieved insight into the thermo‐hydro‐mechanical processes of fast shearing provides physical evidence to the widely debated hypothesis on the generation of excess pore water pressure due to frictional heating. However, for the tested materials, this effect only occurs after extended shearing and does not lead to a complete loss of shear strength. Based on that and the observed positive rate effects, catastrophic failure seems unlikely for these landslides. At the same time, the results suggest that for less permeable soils, frictional heating may indeed be a source of negative rate effect during very rapid shearing.

The Impact of Saltwater Intrusion on Rice Cultivation and Aquaculture in Ham Tan Commune, Tra Cu District, Tra Vinh Province, Mekong Delta, Vietnam

This article discusses the impact of saltwater intrusion on rice cultivation and aquaculture in Ham Tan commune, Tra Cu District, Tra Vinh Province, Mekong Delta, Vietnam. Based on 15 in-depth interviews and sociological surveys conducted in Ham Tan commune, Tra Cu District, Tra Vinh Province, the article highlights the main findings. Firstly, rice cultivation and aquaculture in Ham Tan are multidimensionally affected by the negative impacts of saltwater intrusion. Secondly, saltwater intrusion reduces crop yields and decreases the area available for rice cultivation. It also increases labor days and investment costs in rice production. Thirdly, saltwater intrusion decreases the productivity of aquaculture. In fact, a significant number of households engaged in aquaculture experienced complete losses due to saltwater intrusion.

BRCA Associated Protein-1 Immuno-Histochemical Stain in Diagnosis of Malignant Mesothelioma

Objective: To differentiate malignant mesothelioma from benign mesothelial proliferations and other histological mimickers such as adenocarcinoma and squamous cell carcinoma, utilizing BRCA Associated protein1 (BAP1) immune-histochemical stain.
 Study Design: Retrospective longitudinal study.
 Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore Pakistan, from 2015 to 2020.
 Methodology: We examined BAP1 IHC expression in 82 cases, including 56 malignant mesotheliomas, 12 Adenocarcinomas, and 14 Squamous cell carcinomas. Fifty-six malignant mesotheliomas included 49 epithelioid, 6 Biphasic and one sarcomatoid subtype. Loss of expression was established for cases showing complete loss of nuclear staining.
 Results: Of 56 malignant mesotheliomas, 38(67.85%) showed loss of BAP1 expression, whereas 18(32.14%) showed retained expression. Of 12 adenocarcinoma cases, 10(83.33%) showed retained expression. Similarly, out of 14 squamous cell carcinomas, 12(85.71%) showed retained expression.
 Conclusion: Loss of nuclear expression of BAP1 IHC serves as a valuable diagnostic ancillary tool in distinguishing malignant mesothelioma from its histological mimickers.Keywords: BAP1, Immunohistochemistry, Malignant mesothelioma.

SLC6A1 variant pathogenicity, molecular function and phenotype: a genetic and clinical analysis.

Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants and functional data for 184 variants (14.1% lp/p). Clinical and functional data were available for a subset of 126 individuals. We explored the potential associations of variant positions on the GAT1 3D structure with variant pathogenicity, altered molecular function and phenotype severity using bioinformatic approaches. The GAT1 transmembrane domains 1, 6 and extracellular loop 4 (EL4) were enriched for patient over population variants. Across functionally tested missense variants (n = 156), the spatial proximity from the ligand was associated with loss-of-function in the GAT1 transporter activity. For variants with complete loss of in vitro GABA uptake, we found a 4.6-fold enrichment in patients having severe disease versus non-severe disease (P = 2.9 × 10-3, 95% confidence interval: 1.5-15.3). In summary, we delineated associations between the 3D structure and variant pathogenicity, variant function and phenotype in SLC6A1-related disorders. This knowledge supports biology-informed variant interpretation and research on GAT1 function. All our data can be interactively explored in the SLC6A1 portal (https://slc6a1-portal.broadinstitute.org/).

Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles.

Liposomal formulations offer significant advantages as anticancer drug carriers for targeted drug delivery; however, due to their complexity, clinical translation has been challenging. In addition, liposomal product manufacturing has been interrupted in the past, as was the case for Doxil® (doxorubicin hydrochloride liposome injection). Here, interfacial tension (IFT) measurements were investigated as a potential physicochemical characterization tool to aid in liposomal product characterization during development and manufacturing. A pendant drop method using an optical tensiometer was used to measure the interfacial tension of various analogues of Doxil® liposomal suspensions in air and in dodecane. The effect of liposome concentration, formulation (PEG and cholesterol content), presence of encapsulated drug, as well as average particle size was analyzed. It was observed that Doxil® analog liposomes demonstrate surfactant-like behavior with a sigmoidal-shape interfacial tension vs. concentration curve. This behavior was heavily dependent on PEG content, with a complete loss of surfactant-like behavior when PEG was removed from the formulation. In addition to interfacial tension, three data analyses were identified as able to distinguish between formulations with variations in PEG, cholesterol, and particle size: (i) polar and non-polar contribution to interfacial tension, (ii) liposomal concentration at which the polar and non-polar components were equal, and (iii) rate of interfacial tension decay after droplet formation, which is indicative of how quickly liposomes migrate from the bulk of the solution to the surface. We demonstrate for the first time that interfacial tension can be used to detect certain liposomal formulation changes, such as PEG content, encapsulated drug presence, and size variability, and may make a useful addition to physicochemical characterization during development and manufacturing of liposomal products.

Genetic and Immunohistochemistry Tools to Visualize Rat Macrophages In Situ.

Macrophages contribute to many aspects of development and homeostasis, innate and acquired immunity, immunopathology, and tissue repair. Every tissue contains an abundant resident macrophage population. Inflammatory stimuli promote the recruitment of monocytes from the blood and their adaptation promotes the removal of the stimulus and subsequent restoration of normal tissue architecture. Dysregulation of this response leads to chronic inflammation and tissue injury. In many tissues, their differentiation and survival are dependent on the colony stimulating factor 1 receptor (CSF1R) signalling axis, which is highly conserved across all vertebrates. Complete loss of either CSF1R or its cognate ligands, colony stimulating factor 1 (CSF1), and interleukin 34 (IL-34), results in the loss of many tissue-resident macrophage populations. This provides a useful paradigm to study macrophages.There are many tools used to visualize tissue-resident macrophages and their precursors, monocytes, in mice and humans. Particularly in mice there are genetic tools available to delete, enhance and manipulate monocytes and macrophages and their gene products to gain insight into phenotype and function. The laboratory rat has many advantages as an experimental model for the understanding of human disease, but the analytical resources are currently more limited than in mice. Here, we describe available genetic models, antibodies, and immunohistochemistry (IHC) methods that may be used to visualize tissue-resident macrophages in rats.

Revisiting the pedicled circumflex scapular artery (pCSA) perforator flap: From simple to complex locoregional reconstructions

Soft tissue defects involving the axilla and the upper back region are often complex to treat. The complexity of these defects may be extremely different, ranging from superficial skin damage to large loss of substance with lymphatic drainage impairment. The pedicled circumflex scapular artery (pCSA) perforator flap represents a valid procedure in this setting. It can be tailored according to the patient's needs, and its intraseptal pedicle allows a quick dissection with a wide range of motion. Twenty-four consecutive patients treated by means of pCSA perforator flap were included. All the flaps were pedicled and were used for locoregional reconstructions. The etiology of the defects was an oncologic resection in 15 cases, acne/hidradenitis suppurativa resection in 6 cases, lymphatic complication in 2 cases, and burn in 1 case. Patients' mean age was 61 years old; seventeen were males and seven were females. All the patients were successfully treated with good aesthetic and functional results. One patient presented with a wound dehiscence, which required secondary surgical treatment. No partial or complete flap losses were encountered. Primary closure of the donor site was achieved in all cases. The mean follow-up period was 10.5 months (range 6-12). This case series shows the reliability and versatility of the pCSA perforator flap for locoregional reconstructions. Because of its rich vascularisation, extensive or unconventionally-shaped flaps are possible. Moreover, its lymphatic rich tissues make it suitable for the treatment of complications related to axillary lymphadenectomy.

Purification and characterization of extracellular PHB depolymerase enzyme from Aeromonas caviae Kuk1-(34) and their biodegradation studies with polymer films.

PHB depolymerase enzymes are able to breakdown the PHB polymers and thereby get significant economic value in the bioplastics industry and for bioremediation as well. This study shows the purification of novel extracellular PHB depolymerase enzyme from Aeromonas caviae Kuk1-(34) using dialysis followed by gel filtration and HPLC. The purification fold and yield after HPLC were 45.92 and 27.04%, respectively. HPLC data showed a single peak with a retention time of 1.937min. GC-MS analysis reveals the presence of three compounds, of which 1-Dodecanol was found to be most significant with 54.48% area and 8.623-min retention time (RT). The molecular weight of the purified enzyme was obtained as 35kDa with Km and apparent Vmax values of 0.769mg/mL and 1.89 U/mL, respectively. The enzyme was moderately active at an optimum temperature of 35 °C and at pH 8.0. The stability was detected at pH 7.0-9.0 and 35-45 °C. Complete activity loss was observed with EDTA, SDS, Tween-20 at 5 mM and with 0.1% Triton X 100. A biodegradation study of commercially available biodegradable polymer films was carried out in a liquid medium and in soil separately with pure microbial culture and with purified enzyme for 7, 14, 28, and 49 consecutive days. In a liquid medium, with a pure strain of Aeromonas caviae Kuk1-(34), the maximum degradation (89%) was achieved on the PHB film, while no changes were observed with other polymer films. With purified enzyme in the soil, 71% degradation of the PHB film was noticed, and it was only 18% in the liquid medium. All such weight analysis were confirmed by SEM images where several holes, pits, grooves, crest, and surface roughness are clearly observed. Our results demonstrated the potential utility of Aeromonas caviae Kuk1-(34) as a source of extracellular PHB depolymerase capable of degrading PHB under a wide range of natural/ lab conditions.

Storage Temperature and Grain Moisture Effects on Market and End Use Properties of Red Lentil

Storing lentil is a strategy used by growers to manage price volatility. However, studies investigating the impact of storage conditions on the market and end use properties of lentil are limited. This study examined the effects of storage temperature (4, 15, 25, and 35 °C) and grain moisture (10 and 14%, w/w) on traits related to market (seed coat colour), viability (germination capacity), and end use properties (hydration capacity, milling efficiency, and cooking quality) in four red lentil cultivars (PBA Bolt, PBA Hallmark, PBA Hurricane, PBA Jumbo2) over 360 days. Storing lentil at 14% moisture content and 35 °C significantly (p = 0.05) darkened seed coat after 30 days, caused complete loss of viability within 180 days and reduced cooking quality (cooked firmness) after 120 days across all tested cultivars. Storing lentil at 10% moisture content and 35 °C reduced hydration capacity after 30 days, and milling efficiency after 120 days across all cultivars tested. PBA Jumbo2 exhibited a higher rate of degradation in hydration capacity and cooking quality, and a lower rate of degradation in the other traits studied. Storing lentil at ≤15 °C prevented degradation of all quality traits. These findings will support improved lentil storage protocols to maintain quality and improve economic outcomes for the pulse industry.

Genetic mapping and transcriptome profiling of a chickpea (Cicer arietinum L.) mutant identifies a novel locus (CaEl) regulating organ size and early vigor.

Chickpea is among the top three legumes produced and consumed worldwide. Early plant vigor, characterized by good germination and rapid seedling growth, is an important agronomic trait in many crops including chickpea, and shows a positive correlation with seed size. In this study, we report a gamma-ray-induced chickpea mutant with a larger organ and seed size. The mutant (elm) exhibits increased early vigor and contains higher proline that contributes to a better tolerance under salt stress at germination, seedling, and early vegetative phase. The trait is governed as monogenic recessive, with wild-type allele being incompletely dominant over the mutant. Genetic mapping of this locus (CaEl) identified it as a previously uncharacterized gene (101503252) in chromosome 1 of the chickpea genome. There is a deletion of this gene in the mutant with a complete loss of expression. In silico analysis suggests that the gene is present as a single copy in chickpea and related legumes of the galegoid clade. In the mutant, cell division and expansion are affected. Transcriptome profiling identified differentially regulated transcripts related to cell division, expansion, cell wall organization, and metabolism in the mutant. The mutant can be exploited in chickpea breeding programs for increasing plant vigor and seed size.

Corneal Sensitivity Is Inversely Correlated With Severity of Diabetic Retinopathy in a Predominantly Underrepresented Population

PurposeTo assess the relationship between diabetic retinopathy (DR) and corneal sensitivity. MethodsIn this prospective study, 100 eyes of 50 patients from primarily underrepresented racial and ethnic backgrounds with DR underwent assessment of corneal sensitivity using a Cochet-Bonnet esthesiometer. Severity of DR was graded by a masked reading center. Corneal sensitivity was compared in eyes with current or regressed proliferative DR (PDR) (n=35) and eyes with non-proliferative DR (NPDR) with no history of PDR (n=65). Corneal sensitivity in eyes that regressed from PDR to NPDR with anti-vascular endothelial growth factor (VEGF) therapy (n=7) was compared to treatment-naïve eyes with no current or prior PDR (n=55) and to eyes with newly diagnosed, treatment-naïve PDR (n=12). ResultsIn eyes with current or prior PDR, the median corneal sensitivity (average of 4 quadrants) was 0.5 cm (IQR 0-3.375), while in eyes with no current or prior PDR, the median corneal sensitivity was 4.75 cm (IQR 2.0-6.0, P<.0001). The median corneal sensitivity in eyes with regressed PDR was 0 cm (IQR 0-0.875), significantly lower than eyes with no current or prior PDR (4.5 cm, IQR 4.0, P=.0076) and no different than eyes with untreated PDR (0 cm, IQR 1.25). The odds of eyes with DRSS ≥ 60 having complete corneal sensitivity loss was 3.6 times that of eyes with NPDR. ConclusionsCorneal sensitivity is impaired in eyes with PDR compared to NPDR, and is not rescued by anti-VEGF therapy. Assessment of corneal sensitivity in eyes with DR may identify patients at risk for additional complications including neurotrophic keratopathy.