Ecological and human health risk assessments of cyanotoxins and heavy metals in a drinking water supply reservoir.

Human beings are frequently exposed to a mixture of chemical pollutants through the ingestion of contaminated drinking water. The present study aimed to assess the ecological and human health risks associated with the contamination of cyanotoxins and heavy metals in a drinking water supply reservoir, the Tri An Reservoir (TAR), in Vietnam. Results demonstrated that the concentrations of individual heavy metals varied in the following order: iron (Fe) > lead (Pb) > arsenic (As) > zinc (Zn). Although the ecological potential risk of heavy metals was low during the study period, the concentration of Fe sometimes exceeded the Vietnamese standard for drinking water. Toxic cyanobacteria and microcystins (MCs) frequently occurred in the TAR with the highest density of 198.7 × 103 cells/mL and 7.8 µg/L, respectively, indicating a high risk of health impacts to humans. The results of the study indicate that exposure to heavy metals does not pose any non-carcinogenic health risks for both adults and children. However, the contamination of MCs in the surface water posed a serious disease enhancement to both adults and children through direct ingestion and dermal absorption.

The Update Immune-Regulatory Role of Pro- and Anti-Inflammatory Cytokines in Recurrent Pregnancy Losses.

Recurrent pregnancy losses (RPL) is a common reproductive disorder with various underlying etiologies. In recent years, rapid progress has been made in exploring the immunological mechanisms for RPL. A propensity toward Th2 over Th1 and regulatory T (Treg) over Th17 immune responses may be advantageous for reproductive success. In women with RPL and animals prone to abortion, an inordinate expression of cytokines associated with implantation and early embryo development is present in the endometrium or decidua secreted from immune and non-immune cells. Hence, an adverse cytokine milieu at the maternal-fetal interface assaults immunological tolerance, leading to fetal rejection. Similar to T cells, NK cells can be categorized based on the characteristics of cytokines they secrete. Decidual NK (dNK) cells of RPL patients exhibited an increased NK1/NK2 ratio (IFN-γ/IL-4 producing NK cell ratios), leading to pro-inflammatory cytokine milieu and increased NK cell cytotoxicity. Genetic polymorphism may be the underlying etiologies for Th1 and Th17 propensity since it alters cytokine production. In addition, various hormones participate in cytokine regulations, including progesterone and estrogen, controlling cytokine balance in favor of the Th2 type. Consequently, the intricate regulation of cytokines and hormones may prevent the RPL of immune etiologies. Local or systemic administration of cytokines or their antagonists might help maintain adequate cytokine milieu, favoring Th2 over Th1 response or Treg over Th17 immune response in women with RPL. Herein, we provided an updated comprehensive review regarding the immune-regulatory role of pro- and anti-inflammatory cytokines in RPL. Understanding the roles of cytokines involved in RPL might significantly advance the early diagnosis, monitoring, and treatment of RPL.

The Drug Shortage Crisis in the United States: Impact on Cancer Pharmaceutical Safety.

Drug shortages pose a significant public health concern in the United States, and cancer drugs are among those most affected. Shortages present serious safety risks for patients and substantial burden on providers and the healthcare system. Multifaceted drivers of this complex problem include manufacturing disruptions, raw material shortages, regulatory issues, market dynamics, and limited financial incentives that reward quality and production of off-patent drugs. Oncology drugs in short supply have resulted in substitution of less effective or more toxic alternatives, medication errors, and treatment delays, and are especially concerning for medications with no adequate substitute. Consequently, patient outcomes such as disease progression and survival have been adversely affected. Furthermore, emerging gray markets have contributed to cost-prohibitive markups and introduction of counterfeit products that compromise patient safety. The Food and Drug Administration plays a key role in preventing and managing pharmaceutical shortages, largely through regulations requiring early notification of manufacturing interruptions. Other proposed strategies similarly target upstream causes and center on reducing regulatory hurdles for manufacturers and increasing incentives for market entry and quality improvement. Despite progress in preventing supply disruptions, continued exploration of underlying systemic drivers remains critical to informing long-term solutions and alleviating the clinical and economic impact of drug shortages.

New Developments in Surgery for Endometriosis and Pelvic Pain.

Endometriosis is a common disease affecting reproductive age women. Pain is one of the most common symptoms associated with endometriosis. When medical therapy has failed or in known deeply infiltrating endometriosis, surgical management is warranted. Laparoscopy is the gold standard for diagnosis and treatment of endometriosis. Recent developments in surgery have shown the feasibility of robotic surgery for endometriosis, although these methods have not been shown to be superior to conventional laparoscopy. Enhanced imaging techniques including fluorescence imaging and narrow band imaging have also been studied. However, long-term clinical benefits have yet to be demonstrated.

Bright X-Ray Source from a Laser-Driven Microplasma Waveguide.

Owing to the rapid progress in laser technology, very high-contrast femtosecond laser pulses of relativistic intensities have become available. These pulses allow for interaction with microstructured solid-density plasma without destroying the structure by parasitic prepulses. This opens a new realm of possibilities for laser interaction with micro- and nanoscale photonic materials at relativistic intensities. Here we demonstrate, for the first time, that when coupled with a readily available 1.8 J laser, a microplasma waveguide (MPW) may serve as a novel compact x-ray source. Electrons are extracted from the walls and form a dense helical bunch inside the channel. These electrons are efficiently accelerated and wiggled by the waveguide modes in the MPW, which results in a bright, well-collimated emission of hard x rays in the range of 1∼100 keV.

Fine-tuning DETR: Toward holistic process in plastic waste sorting system.

Every year human discharges about 350 million tons of plastic waste into the environment and can be projected to triple in 2060 without any attempts to change situation. From 1970 to 2019, an estimation of 130 million tons of plastic waste was accumulated into the rivers, lakes and sea, while only 27 % is recycled and utilized. Moreover, waste treatment plants in most places around the world are using out-of-date technology, may pose a threat to the health of the workers. Therefore, it is essential to modernize these systems for protecting human health. This paper proposes fine-tuning DETR, which applies Artificial Intelligent in plastic waste sorting system. Consequently, this study analyzed the applicability of fine-tuning DETR in the domain of plastic waste categorization and its potential drawbacks. For fair experiment and evaluation, model candidates were trained and evaluated on an industrial plastic waste dataset. The fine-tuning DETR outperformed other candidates in the context of critical indicators, from accuracy (25.1 mAP), processing speed (28 FPS) to computational cost (GFLOPs 86). Furthermore, fine-tuning DETR possesses the capability of autonomous operation without requiring human intervention, distinguishing this candidate from other prevalent algorithms. Our research demonstrates that, fine-tuning DETR specifically and Transformer-based algorithms in general, are entirely suitable and hold significant potential for large-scale application in holistic plastic waste sorting systems.

Navigating veterans with an abnormal prostate cancer screening test: a quasi-experimental study.

BACKGROUND: Prostate cancer disproportionately affects low-income and minority men. This study evaluates the impact of a patient navigation intervention on timeliness of diagnostic resolution and treatment initiation among veterans with an abnormal prostate cancer screen. METHODS: Participants were enrolled between 2006 and 2010. The intervention involved a social worker and lay health worker navigation team that assisted patients in overcoming barriers to care. For navigated (n = 245) versus control (n = 245) participants, we evaluated rates of diagnostic resolution and treatment and adjusted for race, age, and Gleason score. RESULTS: Of 490 participants, 68% were African American, 47% were ≥ 65 years old, and 35% had cancer. Among those with an abnormal screen, navigation did not have a significant effect on time to diagnostic resolution compared to controls (median days of 97 versus 111; adj. HR 1.17, 95% CI, 0.96-1.43, p = 0.12). On analysis of the period beyond 80 days, navigated men reached resolution faster than controls (median of 151 days versus 190 days; adj. HR 1.41, 95% CI, 1.07-1.86, p = 0.01). Among those with cancer, navigation did not have a significant effect on time to treatment initiation compared to controls (median of 93 days versus 87 days; adj. HR 1.15, 95% CI, 0.82-1.62, p = 0.41). CONCLUSION: Our navigation program did not significantly impact the overall time to resolution or treatment for men with prostate cancer compared to controls. The utility of navigation programs may extend beyond targeted navigation times, however, and future studies focusing on other outcomes measures are therefore needed.

Perceptions of patient-provider communication in breast and cervical cancer-related care: a qualitative study of low-income English- and Spanish-speaking women.

To explore patient perceptions of patient-provider communication in breast and cervical cancer-related care among low-income English- and Spanish-speaking women, we examined communication barriers and facilitators reported by patients receiving care at safety net clinics. Participants were interviewed in English or Spanish after receiving an abnormal breast or cervical cancer screening test or cancer diagnosis. Following an inductive approach, interviews were coded and analyzed by the language spoken with providers and patient-provider language concordance status. Of 78 participants, 53 % (n = 41) were English-speakers and 47 % (n = 37) were Spanish-speakers. All English-speakers were language-concordant with providers. Of Spanish-speakers, 27 % (n = 10) were Spanish-concordant; 38 % (n = 14) were Spanish-discordant, requiring an interpreter; and 35 % (n = 13) were Spanish mixed-concordant, experiencing both types of communication throughout the care continuum. English-speakers focused on communication barriers, and difficulty understanding jargon arose as a theme. Spanish-speakers emphasized communication facilitators related to Spanish language use. Themes among all Spanish-speaking sub-groups included appreciation for language support resources and preference for Spanish-speaking providers. Mixed-concordant participants accounted for the majority of Spanish-speakers who reported communication barriers. Our data suggest that, although perception of patient-provider communication may depend on the language spoken throughout the care continuum, jargon is lost when health information is communicated in Spanish. Further, the respective consistency of language concordance or interpretation may play a role in patient perception of patient-provider communication.

Polarimetric imaging combining optical parameters for classification of mice non-melanoma skin cancer tissue using machine learning.

Polarimetric imaging systems combining machine learning is emerging as a promising tool for the support of diagnosis and intervention decision-making processes in cancer detection/staging. A present study proposes a novel method based on Mueller matrix imaging combining optical parameters and machine learning models for classifying the progression of skin cancer based on the identification of three different types of mice skin tissues: healthy, papilloma, and squamous cell carcinoma. Three different machine learning algorithms (K-Nearest Neighbors, Decision Tree, and Support Vector Machine (SVM)) are used to construct a classification model using a dataset consisting of Mueller matrix images and optical properties extracted from the tissue samples. The experimental results show that the SVM model is robust to discriminate among three classes in the training stage and achieves an accuracy of 94 % on the testing dataset. Overall, it is provided that polarimetric imaging systems and machine learning algorithms can dynamically combine for the reliable diagnosis of skin cancer.

Effects of pulsatile intravenous follicle-stimulating hormone treatment on ovarian function in women with obesity.

OBJECTIVE: To establish conditions for effective hypothalamic suppression in women with normal and high body mass index (BMI) and test the hypothesis that intravenous (IV) administration of pulsatile recombinant follicle-stimulating hormone (rFSH) can overcome the clinically evident dysfunctional pituitary-ovarian axis in women with obesity. DESIGN: Prospective interventional study. SETTING: Academic medical center. PATIENT(S): Twenty-seven normal-weight women and 27 women with obesity, who were eumenorrheic and aged 21-39 years. INTERVENTION(S): Two-day frequent blood sampling study, in early follicular phase, before and after cetrorelix suppression of gonadotropins and exogenous pulsatile IV rFSH administration. MAIN OUTCOME MEASURE(S): Serum inhibin B and estradiol (E2) levels (basal and rFSH stimulated). RESULT(S): A modified gonadotropin-releasing hormone antagonism protocol effectively suppressed production of endogenous gonadotropins in women with normal and high BMIs, providing a model to address the functional role of FSH in the hypothalamic-pituitary-ovarian axis. The IV rFSH treatment resulted in equivalent serum levels and pharmacodynamics in normal-weight women and those with obesity. However, women with obesity exhibited reduced basal levels of inhibin B and E2 and a significantly decreased response to FSH stimulation. The BMI was inversely correlated with serum inhibin B and E2. In spite of this observed deficit in ovarian function, pulsatile IV rFSH treatment in women with obesity resulted in E2 and inhibin B levels comparable with those in normal-weight women, in the absence of exogenous FSH stimulation. CONCLUSION(S): Despite normalization of FSH levels and pulsatility by exogenous IV administration, women with obesity demonstrate ovarian dysfunction with respect to E2 and inhibin B secretion. Pulsatile FSH can partially correct the relative hypogonadotropic hypogonadism of obesity, thereby providing a potential treatment strategy to mitigate some of the adverse effects of high BMI on fertility, assisted reproduction, and pregnancy outcomes. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov #NCT02478775.

Expression and T cell regulatory action of the PD-1 immune checkpoint in the ovary and fallopian tube.

PROBLEM: Immune cell trafficking and surveillance within the ovary and fallopian tube are thought to impact fertility and also tumorigenesis in those organs. However, little is known of how native cells of the ovary and fallopian tube interact with resident immune cells. Interaction of the Programmed Cell Death Protein-1 (PD-1/PDCD-1/CD279) checkpoint with PD-L1 is associated with downregulated immune response. We have begun to address the question of whether PD-1 ligand or its receptors (PD-L1/-L2) can regulate immune cell function in these tissues of the female reproductive tract. METHOD OF STUDY: PD-1 and ligand protein expression was evaluated in human ovary and fallopian tube specimens, the latter of which included stages of tubal cell transformation and early tumorigenesis. Ovarian expression analysis included the determination of the proteins in human follicular fluid (HFF) specimens collected during in vitro fertilization procedures. Finally, checkpoint bioactivity of HFF was determined by treatment of separately-isolated human T cells and the measurement of interferon gamma (IFNγ). RESULTS: We show that membrane bound and soluble variants of PD-1 and ligands are expressed by permanent constituent cell types of the human ovary and fallopian tube, including granulosa cells and oocytes. PD-1 and soluble ligands were present in HFF at bioactive levels that control T cell PD-1 activation and IFNγ production; full-length checkpoint proteins were found to be highly enriched in HFF exosome fractions. CONCLUSION: The detection of PD-1 checkpoint proteins in the human ovary and fallopian tube suggests that the pathway is involved in immunomodulation during folliculogenesis, the window of ovulation, and subsequent egg and embryo immune-privilege. Immunomodulatory action of receptor and ligands in HFF exosomes is suggestive of an acute checkpoint role during ovulation. This is the first study in the role of PD-1 checkpoint proteins in human tubo-ovarian specimens and the first examination of its potential regulatory action in the contexts of normal and assisted reproduction.

Design of a prostate cancer patient navigation intervention for a Veterans Affairs hospital.

BACKGROUND: Patient navigation programs have been launched nationwide in an attempt to reduce racial/ethnic and socio-demographic disparities in cancer care, but few have evaluated outcomes in the prostate cancer setting. The National Cancer Institute-funded Chicago Patient Navigation Research Program (C-PNRP) aims to implement and evaluate the efficacy of a patient navigation intervention for predominantly low-income minority patients with an abnormal prostate cancer screening test at a Veterans Affairs (VA) hospital in Chicago. METHODS/DESIGN: From 2006 through 2010, C-PNRP implemented a quasi-experimental intervention whereby trained social worker and lay health navigators worked with veterans with an abnormal prostate screen to proactively identify and resolve personal and systems barriers to care. Men were enrolled at a VA urology clinic and were selected to receive navigated versus usual care based on clinic day. Patient navigators performed activities to facilitate timely follow-up such as appointment reminders, transportation coordination, cancer education, scheduling assistance, and social support as needed. Primary outcome measures included time (days) from abnormal screening to diagnosis and time from diagnosis to treatment initiation. Secondary outcomes included psychosocial and demographic predictors of non-compliance and patient satisfaction. Dates of screening, follow-up visits, and treatment were obtained through chart audit, and questionnaires were administered at baseline, after diagnosis, and after treatment initiation. At the VA, 546 patients were enrolled in the study (245 in the navigated arm, 245 in the records-based control arm, and 56 in a subsample of surveyed control subjects). DISCUSSION: Given increasing concerns about balancing better health outcomes with lower costs, careful examination of interventions aimed at reducing healthcare disparities attain critical importance. While analysis of the C-PNRP data is underway, the design of this patient navigation intervention will inform other patient navigation programs addressing strategies to improve prostate cancer outcomes among vulnerable populations.

The role of immunologic tests for subfertility in the clinical environment.

Unexplained subfertility and implantation failures not only are emotionally and physically distressing but also become a significant obstacle to reproductive-age couples who wish to build their family. Often, the currently recommended evaluation for these couples is significantly limited, and many of causes remain unexplained. To obtain an accurate diagnosis and treatment, proper evidence-based laboratory evaluation should be performed. Immune tests for women with subfertility and implantation failures are essential to recognize the immune etiology and appropriate therapeutic strategies. This review focuses on currently used immune tests for subfertile women.

Combined Mueller matrix imaging and artificial intelligence classification framework for Hepatitis B detection.

Significance: The combination of polarized imaging with artificial intelligence (AI) technology has provided a powerful tool for performing an objective and precise diagnosis in medicine. Aim: An approach is proposed for the detection of hepatitis B (HB) virus using a combined Mueller matrix imaging technique and deep learning method. Approach: In the proposed approach, Mueller matrix imaging polarimetry is applied to obtain 4 × 4 Mueller matrix images of 138 HBsAg-containing (positive) serum samples and 136 HBsAg-free (negative) serum samples. The kernel estimation density results show that, of the 16 Mueller matrix elements, elements M 22 and M 33 provide the best discriminatory power between the positive and negative samples. Results: As a result, M 22 and M 33 are taken as the inputs to five different deep learning models: Xception, VGG16, VGG19, ResNet 50, and ResNet150. It is shown that the optimal classification accuracy (94.5%) is obtained using the VGG19 model with element M 22 as the input. Conclusions: Overall, the results confirm that the proposed hybrid Mueller matrix imaging and AI framework provides a simple and effective approach for HB virus detection.

A structurally diversified linker enhances the immune response to a small carbohydrate hapten.

The tether employed to covalently attach ß-mannan disaccharide glycoconjugates influences the specificity of rabbit antibodies that protect against Candida albicans. Two glycoconjugates containing (1 → 2)-ß-mannan disaccharides linked to chicken serum albumin (CSA) either via a structurally uniform or via a stereodiversified spacer were prepared and evaluated in immunization trials in mice and rabbits. Immunization with conjugate vaccine possessing a structurally diversified linker induced higher IgG titers against Candida albicans cell wall phosphomannan than a conjugate with a structurally uniform linker. These results suggest that affinity maturation and the specific antibody response can be shifted towards recognition of the desired hapten by employing a linker with diversified configuration.

Primary Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G-associated Optic Neuritis Presenting after a Frozen Embryo Transfer.

Myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G-associated optic neuritis (ON) is a newly recognized antibody-mediated demyelinating disease of the central nervous system, resulting in acute visual loss and pain with eye movement. The effects of pregnancy on disease pathogenesis remain incompletely understood. Herein, we present a novel association between a frozen embryo transfer (FET) and the first manifestation of MOG-ON in a previously healthy patient with unexplained infertility. The patient presented with acute bilateral visual loss 3 weeks after a single FET and was found to test positive for MOG antibodies with an otherwise unremarkable workup. The patient's vision returned to baseline with high-dose intravenous methylprednisolone and therapeutic plasma exchange. This is the first published case highlighting an association between MOG-ON and assisted reproductive technology (ART) in a patient without prior risk factors. Further studies are needed to clarify the effects of ART and pregnancy in general on disease pathogenesis.

Nanomolar inhibition of human OGA by 2-acetamido-2-deoxy-d-glucono-1,5-lactone semicarbazone derivatives.

O-GlcNAcylation is a dynamic post-translational modification mediated by O-linked ß-N-acetylglucosamine transferase (OGT) and O-GlcNAc hydrolase (OGA), that adds or removes a single ß-N-acetylglucosamine (GlcNAc) moiety to or from serine/threonine residues of nucleocytosolic and mitochondrial proteins, respectively. The perturbed homeostasis of O-GlcNAc cycling results in several pathological conditions. Human OGA is a promising therapeutic target in diseases where aberrantly low levels of O-GlcNAc are experienced, such as tauopathy in Alzheimer's disease. A new class of potent OGA inhibitors, 2-acetamido-2-deoxy-d-glucono-1,5-lactone (thio)semicarbazones, have been identified. Eight inhibitors were designed and synthesized in five steps starting from d-glucosamine and with 15-55% overall yields. A heterologous OGA expression protocol with strain selection and isolation has been optimized that resulted in stable, active and full length human OGA (hOGA) isomorph. Thermal denaturation kinetics of hOGA revealed environmental factors affecting hOGA stability. From kinetics experiments, the synthesized compounds proved to be efficient competitive inhibitors of hOGA with Ki-s in the range of ∼30-250 nM and moderate selectivity with respect to lysosomal ß-hexosaminidases. In silico studies consisting of Prime protein-ligand refinements, QM/MM optimizations and QM/MM-PBSA binding free energy calculations revealed the factors governing the observed potencies, and led to design of the most potent analogue 2-acetamido-2-deoxy-d-glucono-1,5-lactone 4-(2-naphthyl)-semicarbazone 6g (Ki = 36 nM). The protocol employed has applications in future structure based inhibitor design targeting OGA.

Health risk assessment related to cyanotoxins exposure of a community living near Tri An Reservoir, Vietnam.

Cyanotoxins released by cyanobacteria are currently a concern due to potential impacts on plants, animals, and human health. Many instances of cyanotoxin poisoning have been reported around the world, including acute, chronic, and fatal cases. In recent years, the Tri An Reservoir (TAR) in Vietnam has experienced influxes of cyanotoxins from toxic blue-green algae at levels which exceed the World Health Organization's (WHO) permitted level of 1 µg/L. Previous studies have focused on assessing cyanobacterial diversity, the presence of cyanotoxins in water, or the effect on aquatic plants and animals. Therefore, this study aims to assess the health risks associated with cyanobacteria exposure for people living near the TAR in Dong Nai Province, Vietnam, using the Monte Carlo simulation technique. In total, 120 water samples were collected at five points of the reservoir from 2017 to 2019. Seventy-five local people who have been exposed to the water from the reservoir were interviewed. Microcystin (MC) concentration was measured with a high-pressure liquid chromatography (HPLC) system and was used to assess the health risk to local people. The results showed that the MC concentration in raw water ranged from below detection limit (BDL) to 18.67 µg/L in 2017 and from BDL to 8.6 µg/L in 2019, with the predominant variant being MC-RR. The concentration of MCs in the TAR in 2017 and 2019 exceeded the WHO's permitted level of 1 µg/L by 76% and 19%, respectively. The results showed that the rate of MC exposure likely to cause cancer was approximately 1-5%. The oral exposure rate while bathing was less than 2.5%. Direct oral exposure of cyanobacteria with no carcinogenicity was relatively high (40-50%) and the most affected group was adults.

Reactions of terminal polyynes with benzyl azide.

Terminal di-, tri-, tetra-, and pentaynes substituted with a variety of functional groups react with benzyl azide in the presence of CuSO(4)·5H(2)O and ascorbic acid to give derivatives of 4-ethynyl-, 4-butadiynyl-, 4-hexatriynyl-, and 4-octatetraynyl-1,2,3-triazoles in moderate to good yields. These reactions appear to proceed regioselectively, and functionalization occurs exclusively at the terminal alkyne moiety. As well, no evidence of multiple azide additions to the polyyne framework is observed. X-ray crystallographic analysis of nine derivatives is used to document the regioselectivity of the reaction as well as outline structural characteristics of the 1,2,3-triazole products.

Author Correction: Anti-apoptotic activity of ETB receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.