"RAIL BIOPSY" A Novel and Useful Technique for Hysteroscopic Endometrial Target Biopsy.

STUDY OBJECTIVE: Endometrial biopsy (EB) is one of the most common gynecologic procedures. Office-based EB has replaced procedures involving general/loco-regional anesthesia and cervical dilatation performed in the operating room [1-3]. The Grasp Biopsy seems to be the most appropriate EB technique for reproductive-aged women [1,2,4]. Recently, the Visual D&C performed with hysteroscopic tissue removal devices has shown to be a valid alternative [5]. However, it is often difficult to obtain an adequate specimens in peri/post-menopausal women with hypo/atrophic endometrium [2]. Our aim is to show a novel hysteroscopic EB technique called "Rail Biopsy" which requires widespread and cheap instruments. DESIGN: A step-by-step explanation of surgical techinque with narrated video footage. SETTING: Tertiary Level Academic Hospital "IRCCS Azienda Ospedaliero-Universitaria di Bologna" Bologna, Italy. INTERVENTIONS: We performed the "Rail Biopsy" technique with a 5.0 mm Continuous Flow Operative Hysteroscope with a 30° Lens and a 5Fr operative channel. We identify the endometrial target area (ETA), and we create a first track cutting through the endometrium in a caudo-cranial direction using cold scissors. We repeat the procedure, creating a second parallel track, thus completing our "rail" and isolating a wide ETA. Then, in the caudo-cranial direction, we cut through the stromal layer beneath the ETA. With a 5Fr cold grasping forceps, we clench the cranial edge of the ETA, and we remove it from the uterine cavity. A high-quality specimen, even in the case of hypo/atrophic endometrium or focal sessile lesions, can be obtained with this technique. The crucial aspect of the "Rail Biopsy" indeed is cutting through the stromal tissue while the endometrium is minimally touched, avoiding thermal damage deriving from electrosurgery. The instruments required are widespread and cheap. Moreover, this technique can be performed on any wall of the uterus, under vision, and, in the majority of patients, in an office-setting without cervical dilatation or general/loco-regional anesthesia, making it an attractive alternative to hysteroscopy performed in the operating room setting. Further studies comparing "Rail Biopsy" to other EB techniques are needed. CONCLUSION: We showed a novel approach for hysteroscopic EB that may be particularly useful in patients with hypo/atrophic endometrium, easy to learn and with low costs. VIDEO ABSTRACT.

Got milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats.

Previous studies have underscored the importance of breastfeeding and parental care on offspring development and behavior. However, their contribution as dynamic variables in animal models of early life stress are often overlooked. In the present study, we investigated how lipopolysaccharide (LPS)-induced maternal immune activation (MIA) on postnatal day (P)10 affects maternal care, milk, and offspring development. MIA was associated with elevated milk corticosterone concentrations on P10, which recovered by P11. In contrast, both milk triglyceride and percent creamatocrit values demonstrated a prolonged decrease following inflammatory challenge. Adolescent MIA offspring were heavier, which is often suggestive of poor early life nutrition. While MIA did not decrease maternal care quality, there was a significant compensatory increase in maternal licking and grooming the day following inflammatory challenge. However, this did not protect against disrupted neonatal huddling or later-life alterations in sensorimotor gating, conditioned fear, mechanical allodynia, or reductions in hippocampal parvalbumin expression in MIA offspring. MIA-associated changes in brain and behavior were likely driven by differences in milk nutritional values and not by direct exposure to LPS or inflammatory molecules as neither LPS binding protein nor interleukin-6 milk levels differed between groups. These findings reflected comparable microbiome and transcriptomic patterns at the genome-wide level. Animal models of early life stress can impact both parents and their offspring. One mechanism that can mediate the effects of such stressors is changes to maternal lactation quality which our data show can confer multifaceted and compounding effects on offspring physiology and behavior.

The mechanisms of selective attention in phenomenal consciousness.

In three experiments we investigated the effects of selective attention in iconic memory and fragile-visual short-term memory (VSTM), which have been related to phenomenal consciousness. We used a novel retro-cue paradigm with different delays (early vs late) and object priorities (high vs equal vs low), to investigate (a) attentional costs and benefits and the role of (b) bottom-up factors and (c) fragile-VSTM in feature-based attentional selection. Experiment 1 showed that attentional costs modulate visual maintenance at longer delays, while Experiment 2 showed that by reducing the time exposure of the memory array from 250 ms to 100 ms, as a bottom-up factor, participants were not able to select the objects based on their priorities. Finally, Experiment 3 showed that a pattern mask presented before the transfer in visual working memory, attenuates the overall performance while preserving the priority effect. The implications for phenomenal consciousness before conscious access are discussed.

Impacts of climate and land use change on groundwater recharge under shared socioeconomic pathways: A case of Siem Reap, Cambodia.

The rapid pace of urbanization blended with climate change has significantly altered surface and groundwater flows. In the context of tourism-driven economic potential areas, these drivers have greater effects, including threatening groundwater availability. This study assessed the combined impacts of climate and land use changes on the groundwater recharge (GWR) in Siem Reap, Cambodia utilizing Phase Six of the Coupled Model Intercomparison Project (CMIP6) global climate models (GCMs), DynaCLUE land-use model, and Soil Water Assessment Tool (SWAT). Three climate models CanESM5, EC_Earth3, and MIROC6, out of seven, best captured the observed data after performance evaluation through the entropy method, were bias-corrected linearly for two shared socioeconomic pathways (SSPs) - SSP2-4.5 and SSP5-8.5. The results indicate a general increase in precipitation under both SSPs, while the average annual maximum temperature is likely to increase by 0.024 °C/year and 0.049 °C/year under SSP2-4.5 and SSP5-8.5, respectively. A similar trend but relatively higher increase is expected for the minimum temperature. Furthermore, the historical land use change showed the expansion of urban settlement by 373% between 2004 and 2019 at the expense of forest and shrubland. Future land use projections from the DynaCLUE model show that the urban settlements in the study area are likely to expand, from their 2019 condition, by 55% in 2030, 209% in 2060, and 369% in 2090 under SSP2 and at double of these rates under SSP5 scenario. The GWR is expected to rise by 39-53% during the wet season and decrease by 13-29% during the dry season under both scenarios. Meanwhile, under constant land use, the GWR is likely to increase more compared to other scenarios, highlighting the importance of land use planning to policymakers and planners. Additionally, the study shall also be important to practitioners and researchers in understanding, planning, and evaluating the performance of multiple climate models in groundwater assessment.

Assessing the future climate change, land use change, and abstraction impacts on groundwater resources in the Tak Special Economic Zone, Thailand.

Groundwater is an important source of water supply in the Tak Special Economic Zone of Thailand. However, groundwater is under stress from climate change, land use change, and an increase in abstraction, affecting the groundwater level and its sustainability. Therefore, this study analyses the impact of these combined stresses on groundwater resources in the near, mid, and far future. Three Global Climate Models are used to project the future climate under SSP2-4.5 and SSP5-8.5 scenarios. According to the results, both maximum and minimum temperatures are likely to show similar increasing trends for both scenarios, with a rise of approximately 1 (1.5), 2 (3), and 3 (5) °C expected for SSP2-4.5 (SSP5-8.5) in each consecutive period. Annual rainfall is expected to continually increase in the future, with around 1500-1600 mm in rainfall (11ꟷ5.43% higher). Land use change is predicted for two scenarios: business as usual (BU) and rapid urbanisation (RU). The forest area is expected to increase to 30% (35%) coverage in 2090 for BU (RU) while agriculture is likely to reduce to 60% (50%) with the urban area increasing to 2.4% (7%). Water demand is predicted to increase in all future scenarios. The SWAT model is used to project recharge, which is likely to increase by 10-20% over time. The highest increase is predicted in the far future under SSP2 and RU scenarios. MODFLOW was used to project future groundwater resources, but due to the lack of consistent data, the time scale is reduced to yearly simulation. The results reveal that the groundwater level is expected to increase in the central part (urban area) of the study area and decrease along the boundary (agricultural area) of the aquifer. This research can aid policymakers and decision-makers in understanding the impact of multiple stressors and formulating adaptation strategies to manage groundwater resources in special economic zones.

New Insights into Hemopexin-Binding to Hemin and Hemoglobin.

Hemopexin (Hx) is a plasma glycoprotein that scavenges heme (Fe(III) protoporphyrin IX). Hx has important implications in hemolytic disorders and hemorrhagic conditions because releasing hemoglobin increases the labile heme, which is potentially toxic, thus producing oxidative stress. Therefore, Hx has been considered for therapeutic use and diagnostics. In this work, we analyzed and mapped the interaction sequences of Hx with hemin and hemoglobin. The spot-synthesis technique was used to map human hemopexin (P02790) binding to hemin and human hemoglobin. A library of 15 amino acid peptides with a 10-amino acid overlap was designed to represent the entire coding region (aa 1-462) of hemopexin and synthesized onto cellulose membranes. An in silico approach was taken to analyze the amino acid frequency in the identified interaction regions, and molecular docking was applied to assess the protein-protein interaction. Seven linear peptide sequences in Hx were identified to bind hemin (H1-H7), and five were described for Hb (Hb1-Hb5) interaction, with just two sequences shared between hemin and Hb. The amino acid composition of the identified sequences demonstrated that histidine residues are relevant for heme binding. H105, H293, H373, H400, H429, and H462 were distributed in the H1-H7 peptide sequences, but other residues may also play an important role. Molecular docking analysis demonstrated Hx's association with the ß-chain of Hb, with several hotspot amino acids that coordinated the interaction. This study provides new insights into Hx-hemin binding motifs and protein-protein interactions with Hb. The identified binding sequences and specific peptides can be used for therapeutic purposes and diagnostics as hemopexin is under investigation to treat different diseases and there is an urgent need for diagnostics using labile heme when monitoring hemolysis.

B-Cell Epitope Mapping of the Vibrio cholera Toxins A, B, and P and an ELISA Assay.

Oral immunization with the choleric toxin (CT) elicits a high level of protection against its enterotoxin activities and can control cholera in endemic settings. However, the complete B-cell epitope map of the CT that is responsible for protection remains to be clarified. A library of one-hundred, twenty-two 15-mer peptides covering the entire sequence of the three chains of the CT protein (CTP) was prepared by SPOT synthesis. The immunoreactivity of membrane-bound peptides with sera from mice vaccinated with an oral inactivated vaccine (Schankol™) allowed the mapping of continuous B-cell epitopes, topological studies, multi-antigen peptide (MAP) synthesis, and Enzyme-Linked Immunosorbent Assay (ELISA) development. Eighteen IgG epitopes were identified; eight in the CTA, three in the CTB, and seven in the protein P. Three V. cholera specific epitopes, Vc/TxA-3, Vc/TxB-11, and Vc/TxP-16, were synthesized as MAP4 and used to coat ELISA plates in order to screen immunized mouse sera. Sensitivities and specificities of 100% were obtained with the MAP4s of Vc/TxA-3 and Vc/TxB-11. The results revealed a set of peptides whose immunoreactivity reflects the immune response to vaccination. The array of peptide data can be applied to develop improved serological tests in order to detect cholera toxin exposure, as well as next generation vaccines to induce more specific antibodies against the cholera toxin.

Evaluating aquifer stress and resilience with GRACE information at different spatial scales in Cambodia.

Groundwater exploitation for different sectors in Cambodia is expanding. Groundwater levels have already begun to decline in some parts of the country. Monitoring and assessing groundwater storage (GWS) change, aquifer stress and aquifer resilience will support the proper planning and management of the country's groundwater resources; however, information regarding groundwater in Cambodia is currently scarce. Thus, GWS change in Cambodia over the 15 years from April 2002 to March 2017 was assessed using remote-sensing-based Gravity Recovery and Climate Experiment (GRACE) and Global Land Data Assimilation System (GLDAS) datasets, with a comprehensive validation of the GRACE-derived groundwater storage anomaly (GWSA) with respect to in-situ field-based observations. The current study also investigated the impact of surface water storage (SWS) change in Tonle Sap Lake, South-East Asia's largest freshwater lake, on deriving the GWS change in Cambodia. The groundwater aquifer stresses (GAS), and aquifer resilience (AR) were also evaluated. The validation results were promising, with the correlation coefficient between satellite-based estimations and ground-based measurements ranging from 0.82 to 0.88 over four subbasins. The overall decreasing rate of GWS was found to be -0.63 mm/month, with two basins having the highest declining rate of more than 1.4 mm/month. Meanwhile, the aquifer experiencing stress during the dry season had a very low ability to quickly recover from these stresses. These findings emphasise that appropriate management is urgently needed to ensure the sustainability of the groundwater resource system in this country. Supplementary Information: The online version contains supplementary material available at 10.1007/s10040-022-02570-w.

L'exploitation des eaux souterraines s'étend au Cambodge dans différents secteurs. Les niveaux piézométriques ont déjà commencé à baisser sur quelques secteurs du pays. Surveiller et évaluer les changements de stock d'eau souterraine (GWS), la pression sur les aquifères et leur résilience supportera une planification et gestion correctes des ressources en eau dans le pays; toutefois, les informations en relation avec les eaux souterraines sont peu nombreuses aujourd'hui au Cambodge. Ainsi, les changements de GWS au Cambodge sur les 15 dernières années, d'avril 2002 à mars 2017 ont été évalués à l'aide des méthodes de télédétection basées sur le Gravity Recovery and Climate Experiment (GRACE) et les jeux de données du Global Land Data Assimilation System (GLDAS) avec une validation complète des anomalies de stockage d'eau souterraine (GWSA) de GRACE par l'utilisation d'observations de terrain. L'étude a également permis d'étudier l'impact des changements de stocks d'eau de surface (SWS) dans le lac Tonle Sap, le plus grand lac d'eau douce du sud-est asiatique, par dérivation des changements de GWS au Cambodge. Les pressions sur les eaux souterraines (GAS) et la résilience des aquifère (AR) ont également été évaluées. La validation des résultats est prometteuse, avec un coefficient de corrélation entre les estimations basées sur les données satellitaires et les mesures de terrain allant de 0.82 à 0.88 sur quatre sous-bassins. Un taux de baisse globale du GWS de ­0.63 mm/mois a été estimé, avec deux sous-bassins ayant des baisses plus fortes de plus de 1.4 mm/mois. Sur la même période, les aquifère qui subissent un stress durant les basses eaux montrent une faible capacité à récupérer de ce stress. Ces résultats montrent qu'une gestion adéquate est urgemment nécessaire pour assurer la durabilité de la ressource en eau souterraine dans ce pays.

La explotación de las aguas subterráneas para diferentes sectores en Camboya está en expansión. Los niveles de las aguas subterráneas ya han empezado a descender en algunas partes del país. El seguimiento y la evaluación de los cambios en el almacenamiento de las aguas subterráneas (GWS), el estrés del acuífero y la resiliencia del acuífero apoyarán la planificación y la gestión adecuadas de los recursos de aguas subterráneas del país; sin embargo, la información relativa a las aguas subterráneas en Camboya es actualmente escasa. Por lo tanto, se evaluó el cambio de GWS en Camboya durante los últimos 15 años, desde abril de 2002 hasta marzo de 2017, utilizando conjuntos de datos del Gravity Recovery and Climate Experiment (GRACE) y del Global Land Data Assimilation System (GLDAS) basados en la teledetección, con una validación exhaustiva de la anomalía de almacenamiento de aguas subterráneas (GWSA) derivada de GRACE con respecto a las observaciones in situ sobre el terreno. El presente estudio también investigó el impacto del cambio en el almacenamiento de agua superficial (SWS) en el lago Tonle Sap, el mayor lago de agua dulce del sudeste asiático, en la derivación del cambio del GWS en Camboya. También se evaluaron las tensiones de los acuíferos subterráneos (GAS) y la resistencia de los acuíferos (AR). Los resultados de la validación fueron promisorios, ya que el coeficiente de correlación entre las estimaciones basadas en satélites y las mediciones terrestres osciló entre 0.82 y 0.88 en cuatro subcuencas. La tasa global de disminución del GWS fue de ­0.63 mm/mes, con dos cuencas con la tasa de disminución más alta, de más de 1.4 mm/mes. Mientras tanto, el acuífero que experimentaba estrés durante la estación seca tenía una capacidad muy baja para recuperarse rápidamente de estas tensiones. Estos resultados ponen de relieve que se necesita urgentemente una gestión adecuada para garantizar la sostenibilidad del sistema de recursos hídricos subterráneos en este país.

A exploração de águas subterrâneas para diferentes setores no Camboja está se expandindo. Os níveis das águas subterrâneas já começaram a diminuir em algumas partes do país. O monitoramento e avaliação das mudanças no armazenamento de águas subterrâneas (AASub), estresse e resiliência do aquífero apoiarão o planejamento e a gestão adequados dos recursos hídricos subterrâneos do país; no entanto, as informações sobre as águas subterrâneas no Camboja são atualmente escassas. Assim, a mudança de AASub no Camboja nos últimos 15 anos, de abril de 2002 a março de 2017, foi avaliada usando conjuntos de dados Gravity Recovery and Climate Experiment (GRACE) e Global Land Data Assimilation System (GLDAS) baseados em sensoriamento remoto, com uma validação abrangente da anomalia de armazenamento de água subterrânea derivada do GRACE (AAASub) em relação a observações baseadas em campo. O estudo atual também investigou o impacto da mudança de armazenamento de água de superfície (AASup) no Lago Tonle Sap, o maior lago de água doce do Sudeste Asiático, na derivação da mudança de AASub no Camboja. Os estresses das águas subterrâneas no aquífero (SASub) e a resiliência do aquífero (RA) também foram avaliados. Os resultados da validação foram promissores, com o coeficiente de correlação entre as estimativas baseadas em satélite e as medições terrestres variando de 0.82 a 0.88 em quatro sub-bacias. A taxa global decrescente de AAS foi de ­0.63 mm/mês, com duas bacias tendo a maior taxa de declínio de mais de 1.4 mm/mês. Enquanto isso, o aquífero submetido a estresse durante a estação seca teve uma capacidade muito baixa de se recuperar rapidamente desses estresses. Esses achados enfatizam que uma gestão adequada é urgentemente necessária para garantir a sustentabilidade do sistema de recursos hídricos subterrâneos neste país.

Potent Activity of a High Concentration of Chemical Ozone against Antibiotic-Resistant Bacteria.

BACKGROUND: Health care-associated infections (HAIs) are a significant public health problem worldwide, favoring multidrug-resistant (MDR) microorganisms. The SARS-CoV-2 infection was negatively associated with the increase in antimicrobial resistance, and the ESKAPE group had the most significant impact on HAIs. The study evaluated the bactericidal effect of a high concentration of O3 gas on some reference and ESKAPE bacteria. MATERIAL AND METHODS: Four standard strains and four clinical or environmental MDR strains were exposed to elevated ozone doses at different concentrations and times. Bacterial inactivation (growth and cultivability) was investigated using colony counts and resazurin as metabolic indicators. Scanning electron microscopy (SEM) was performed. RESULTS: The culture exposure to a high level of O3 inhibited the growth of all bacterial strains tested with a statistically significant reduction in colony count compared to the control group. The cell viability of S. aureus (MRSA) (99.6%) and P. aeruginosa (XDR) (29.2%) was reduced considerably, and SEM showed damage to bacteria after O3 treatment Conclusion: The impact of HAIs can be easily dampened by the widespread use of ozone in ICUs. This product usually degrades into molecular oxygen and has a low toxicity compared to other sanitization products. However, high doses of ozone were able to interfere with the growth of all strains studied, evidencing that ozone-based decontamination approaches may represent the future of hospital cleaning methods.

Regular football training down-regulates miR-1303 muscle expression in veterans.

PURPOSE: Regular exercise affects the expression of several genes, proteins and microRNAs (miRNAs) in time- and intensity-dependent manner promoting longevity. We previously identified from GeneChip Array analysis several differentially expressed genes and miRNAs in muscle from veteran football players (VPG) compared to active untrained elderly subjects (CG); here we focussed on miRNA-1303 (miR-1303). The aims of the present research were: to analyse the effects of football training on the expression of miR-1303 and to identify its putative target involved in the longevity pathways in skeletal muscle from VPG compared to CG. METHODS: RNA samples from 12 VPG and 12 CG muscle biopsies were used to validate miR-1303 expression. Crossing four different bioinformatic algorithms, we identified 16 putative targets of miR-1303; from these, BAG-2, KLHL7 and KBTBD6 were chosen for further validation by Western blot analysis in LHCN-M2 human myoblasts transiently transfected with miR-1303. RESULTS: Football training down-regulates miR-1303 expression in muscle from VPG compared to CG and the expression of BAG-2, a chaperon protein involved in the autophagy pathway, inversely correlated to overexpression of miR-1303 in a time-dependent manner, indicating that it is a miR-1303 potential target. CONCLUSIONS: This is the first report, to our knowledge, describing miR-1303 regulation in skeletal muscle by football training and the identification of a target protein, BAG-2, involved in the autophagy pathway. This result contributes to the enlargement of knowledge on the molecular mechanisms linking football training, autophagy and longevity.

SARS-CoV-2 Proteins Bind to Hemoglobin and Its Metabolites.

(1) Background: coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been linked to hematological dysfunctions, but there are little experimental data that explain this. Spike (S) and Nucleoprotein (N) proteins have been putatively associated with these dysfunctions. In this work, we analyzed the recruitment of hemoglobin (Hb) and other metabolites (hemin and protoporphyrin IX-PpIX) by SARS-Cov2 proteins using different approaches. (2) Methods: shotgun proteomics (LC-MS/MS) after affinity column adsorption identified hemin-binding SARS-CoV-2 proteins. The parallel synthesis of the peptides technique was used to study the interaction of the receptor bind domain (RBD) and N-terminal domain (NTD) of the S protein with Hb and in silico analysis to identify the binding motifs of the N protein. The plaque assay was used to investigate the inhibitory effect of Hb and the metabolites hemin and PpIX on virus adsorption and replication in Vero cells. (3) Results: the proteomic analysis by LC-MS/MS identified the S, N, M, Nsp3, and Nsp7 as putative hemin-binding proteins. Six short sequences in the RBD and 11 in the NTD of the spike were identified by microarray of peptides to interact with Hb and tree motifs in the N protein by in silico analysis to bind with heme. An inhibitory effect in vitro of Hb, hemin, and PpIX at different levels was observed. Strikingly, free Hb at 1mM suppressed viral replication (99%), and its interaction with SARS-CoV-2 was localized into the RBD region of the spike protein. (4) Conclusions: in this study, we identified that (at least) five proteins (S, N, M, Nsp3, and Nsp7) of SARS-CoV-2 recruit Hb/metabolites. The motifs of the RDB of SARS-CoV-2 spike, which binds Hb, and the sites of the heme bind-N protein were disclosed. In addition, these compounds and PpIX block the virus's adsorption and replication. Furthermore, we also identified heme-binding motifs and interaction with hemin in N protein and other structural (S and M) and non-structural (Nsp3 and Nsp7) proteins.

Antiviral Potential of Naphthoquinones Derivatives Encapsulated within Liposomes.

HSV infections, both type 1 and type 2, are among the most widespread viral diseases affecting people of all ages. Their symptoms could be mild, with cold sores up to 10 days of infection, blindness and encephalitis caused by HSV-1 affecting immunocompetent and immunosuppressed individuals. The severe effects derive from co-evolution with the host, resulting in immune evasion mechanisms, including latency and growing resistance to acyclovir and derivatives. An efficient alternative to controlling the spreading of HSV mutations is the exploitation of new drugs, and the possibility of enhancing their delivery through the encapsulation of drugs into nanoparticles, such as liposomes. In this work, liposomes were loaded with a series of 2-aminomethyl- 3-hydroxy-1,4-naphthoquinones derivatives with n-butyl (compound 1), benzyl (compound 2) and nitrobenzene (compound 3) substituents in the primary amine of naphthoquinone. They were previously identified to have significant inhibitory activity against HSV-1. All of the aminomethylnaphthoquinones derivatives encapsulated in the phosphatidylcholine liposomes were able to control the early and late phases of HSV-1 replication, especially those substituted with the benzyl (compound 2) and nitrobenzene (compound 3), which yields selective index values that are almost nine times more efficient than acyclovir. The growing interest of the industry in topical administration against HSV supports our choice of liposome as a drug carrier of aminomethylnaphthoquinones derivatives for formulations of in vivo pre-clinical assays.

Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges.

Advances in carbohydrate chemistry have certainly made common oligosaccharides much more accessible. However, many current methods still rely heavily upon specialized knowledge of carbohydrate chemistry. The application of automated technologies to chemical and life science applications such as genomics and proteomics represents a vibrant field. These automated technologies also present opportunities for their application to organic synthesis, including that of the synthesis of oligosaccharides. However, application of automated methods to the synthesis of carbohydrates is an underdeveloped area as compared to other classes of biomolecules. The overarching goal of this review article is to present the advances that have been made at the interface of carbohydrate chemistry and automated technology.

Hysteroscopic endometrial resection vs. hysterectomy for abnormal uterine bleeding: impact on quality of life and sexuality. Evidence from a systematic review of randomized controlled trials.

PURPOSE OF REVIEW: The aim of this systematic review is to summarize the current evidence regarding the effectiveness of hysterectomy and hysteroscopic endometrial resection in improving quality of life (QoL), sexual function and psychological wellbeing of women abnormal uterine bleeding. RECENT FINDINGS: We performed a systematic literature search in PubMed/MEDLINE and Embase for original studies written in English (registered in PROSPERO 2019 CRD42019133632), using the terms 'endometrial ablation', 'endometrial destruction', 'endometrial resection', 'hysterectomy', 'menorrhagia', 'dysfunctional uterine bleeding', 'quality of life', 'sexuality' published up to April 2019. Our literature search produced 159 records. After exclusions, nine studies were included showing the following results: both types of treatment significantly improve QoL and psychological wellbeing; hysterectomy is associated with higher rates of satisfaction; hysterectomy is not associated with a significant deterioration in sexual function. SUMMARY: Hysterectomy is currently more advantageous in terms of improving abnormal uterine bleeding and satisfaction rates than hysteroscopic endometrial destruction techniques. Furthermore, there is some evidence of a greater improvement in general health for women undergoing hysterectomy. However, high-quality prospective randomized controlled trials should be implemented to investigate the effectiveness of hysterectomy and endometrial ablation in the improvement of QoL outcomes in larger patient cohorts.

Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans.

Presented herein are two complementary approaches to the synthesis of the core N-glycan pentasaccharide. The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the ß-mannosidic linkage at room temperature. The synthesis of the core pentasaccharide was also accomplished using an high-performance liquid chromatography-assisted automated approach. The overall assembly was swift (8 h) and efficient (31%).

Purification of equine IgG3 by lectin affinity and an interaction analysis via microscale thermophoresis.

The availability of purified antibodies is a prerequisite for many applications and the appropriate choice(s) for antibody-purification is crucial. Numerous methods have been developed for the purification of antibodies from different sources with affinity chromatography-based methods being the most extensively utilized. These methods are based on high specificity, easy reversibility and biological interactions between two molecules (e.g., between receptor and ligand or antibody and antigen). However, no simple techniques have yet been described to characterize and purify subclasses of immunoglobulins (Ig) from some animals of biotechnology importance such as equines, which are frequently used to produce biotherapeutic antibodies. The sera of these animals present a large number of Ig classes that have a greater complexity than other animals. The implementation of an effective protocol to purify the desired antibody class/subclasses requires meticulous planning to achieve yields at a high purity. The IgG3 subclass of equine-Ig has recently been used as antigen in a new diagnostic test for allergic responses to horse sera-based therapies. Here, we defined a simple method using Jacalin lectin immobilized on Sepharose beads to prepare highly pure equine IgG3 antibodies with a determination of the affinity constants for Jacalin lectin and horse IgG3.

Ultrasensitive and rapid immuno-detection of human IgE anti-therapeutic horse sera using an electrochemical immunosensor.

Antivenom allergy disease mediated by patient IgE is an important public health care concern. To improve detection of hypersensitive individuals prior to passive antibody therapy, an amperometric immunosensor was developed to detect reactive human IgE. Whole horse IgG3 (hoIgG3) was immobilized onto the surface of carbon or gold screen-printed electrodes through a cross-linking solution of glutaraldehyde on a chitosan film. Sera from persons with a known allergic response to hoIgG3 or non-allergic individuals was applied to the sensor. Bound human IgE (humIgE) was detected by an anti-humIgE antibody through a quantitative amperometric determination by tracking via the electrochemical reduction of the quinone generated from the hydroquinone with the application of a potential of 25 mV. The optimal immunosensor configuration detected reactive humIgE at a dilution of 1:1800 of the human sera that represent a detection limit of 0.5 pg/mL. Stability testing demonstrated that through 20 cycles of a scan, the specificity and performance remained robust. The new immunosensor successfully detected humIgE antibodies reactive against hoIgG3, which could allow the diagnosis of potential allergenic patients needing therapeutic antivenom preparations from a horse.

OFox imidates as versatile glycosyl donors for chemical glycosylation.

Previously we communicated 3,3-difluoroxindole (HOFox) - mediated glycosylations wherein 3,3-difluoro-3H-indol-2-yl (OFox) imidates were found to be key intermediates. Both the in situ synthesis from the corresponding glycosyl bromides and activation of the OFox imidates could be conducted in a regenerative fashion. Herein, we extend this study with the main focus on the synthesis of various OFox imidates and their investigation as glycosyl donors for chemical 1,2-cis and 1,2-trans glycosylation.

Oligopeptidase B and B2: comparative modelling and virtual screening as searching tools for new antileishmanial compounds.

Leishmaniasis are diseases caused by parasites of the genus Leishmania and transmitted to humans by the bite of infected insects of the subfamily Phlebotominae. Current drug therapy shows high toxicity and severe adverse effects. Recently, two oligopeptidases (OPBs) were identified in Leishmania amazonensis, namely oligopeptidase B (OPB) and oligopeptidase B2 (OPB2). These OPBs could be ideal targets, since both enzymes are expressed in all parasite lifecycle and were not identified in human. This work aimed to identify possible dual inhibitors of OPB and OPB2 from L. amazonensis. The three-dimensional structures of both enzymes were built by comparative modelling and used to perform a virtual screening of ZINC database by DOCK Blaster server. It is the first time that OPB models from L. amazonensis are used to virtual screening approach. Four hundred compounds were identified as possible inhibitors to each enzyme. The top scored compounds were submitted to refinement by AutoDock program. The best results suggest that compounds interact with important residues, as Tyr490, Glu612 and Arg655 (OPB numbers). The identified compounds showed better results than antipain and drugs currently used against leishmaniasis when ADMET in silico were performed. These compounds could be explored in order to find dual inhibitors of OPB and OPB2 from L. amazonensis.