Urine biomarkers for Alzheimer's disease: A new opportunity for wastewater-based epidemiology?

While Alzheimer's disease (AD) diagnosis, management, and care have become priorities for healthcare providers and researcher's worldwide due to rapid population aging, epidemiologic surveillance efforts are currently limited by costly, invasive diagnostic procedures, particularly in low to middle income countries (LMIC). In recent years, wastewater-based epidemiology (WBE) has emerged as a promising tool for public health assessment through detection and quantification of specific biomarkers in wastewater, but applications for non-infectious diseases such as AD remain limited. This early review seeks to summarize AD-related biomarkers and urine and other peripheral biofluids and discuss their potential integration to WBE platforms to guide the first prospective efforts in the field. Promising results have been reported in clinical settings, indicating the potential of amyloid ß, tau, neural thread protein, long non-coding RNAs, oxidative stress markers and other dysregulated metabolites for AD diagnosis, but questions regarding their concentration and stability in wastewater and the correlation between clinical levels and sewage circulation must be addressed in future studies before comprehensive WBE systems can be developed.

Omicron and Delta variant prevalence detection and identification during the fourth COVID-19 wave in Mexico using wastewater-based epidemiology.

Objectives: To identify the SARS-CoV-2 variants Delta and Omicron during the fourth wave of the COVID-19 pandemic in Mexico using samples taken from 19 locations in 18 out of the 32 states. Methods: The genetic material concentration was done with PEG/NaCl precipitation, SARS-CoV-2 presence was confirmed by reverse transcriptase-quantitative polymerase chain reaction assay, the variant detection was carried out using a commercial mutation detection panel kit, and variant/mutation confirmation was done by amplicon sequencing of receptor-binding domain target region. The study used 41 samples. Results: The Delta variant was confirmed in two samples during August 2021 (Querétaro and CDMX) and in three samples during November 2021 (Aguascalientes, Ciudad Juárez campuses, and Nuevo Leon). In December 2021, another sample with the Delta variant was confirmed in Nuevo Leon. Between January to March 2022 only the presence of Omicron was confirmed, (variant BA.1). Additionally, in this period six samples were identified with the status "Variant Not Determined". Conclusion: To our knowledge, this study is one of the first to identify Omicron and Delta variants with polymerase chain reaction in Mexico and Latin America and its distribution across the country with 56% Mexican states making it a viable alternative for variant detection without conducting a large quantity of sequencing of clinical tests.

Emerging Applications of Nanobiosensors in Pathogen Detection in Water and Food.

Food and waterborne illnesses are still a major concern in health and food safety areas. Every year, almost 0.42 million and 2.2 million deaths related to food and waterborne illness are reported worldwide, respectively. In foodborne pathogens, bacteria such as Salmonella, Shiga-toxin producer Escherichia coli, Campylobacter, and Listeria monocytogenes are considered to be high-concern pathogens. High-concern waterborne pathogens are Vibrio cholerae, leptospirosis, Schistosoma mansoni, and Schistosima japonicum, among others. Despite the major efforts of food and water quality control to monitor the presence of these pathogens of concern in these kinds of sources, foodborne and waterborne illness occurrence is still high globally. For these reasons, the development of novel and faster pathogen-detection methods applicable to real-time surveillance strategies are required. Methods based on biosensor devices have emerged as novel tools for faster detection of food and water pathogens, in contrast to traditional methods that are usually time-consuming and are unsuitable for large-scale monitoring. Biosensor devices can be summarized as devices that use biochemical reactions with a biorecognition section (isolated enzymes, antibodies, tissues, genetic materials, or aptamers) to detect pathogens. In most cases, biosensors are based on the correlation of electrical, thermal, or optical signals in the presence of pathogen biomarkers. The application of nano and molecular technologies allows the identification of pathogens in a faster and high-sensibility manner, at extremely low-pathogen concentrations. In fact, the integration of gold, silver, iron, and magnetic nanoparticles (NP) in biosensors has demonstrated an improvement in their detection functionality. The present review summarizes the principal application of nanomaterials and biosensor-based devices for the detection of pathogens in food and water samples. Additionally, it highlights the improvement of biosensor devices through nanomaterials. Nanomaterials offer unique advantages for pathogen detection. The nanoscale and high specific surface area allows for more effective interaction with pathogenic agents, enhancing the sensitivity and selectivity of the biosensors. Finally, biosensors' capability to functionalize with specific molecules such as antibodies or nucleic acids facilitates the specific detection of the target pathogens.

Passive Sampler Technology for Viral Detection in Wastewater-Based Surveillance: Current State and Nanomaterial Opportunities.

Although wastewater-based surveillance (WBS) is an efficient community-wide surveillance tool, its implementation for pathogen surveillance remains limited by ineffective sample treatment procedures, as the complex composition of wastewater often interferes with biomarker recovery. Moreover, current sampling protocols based on grab samples are susceptible to fluctuant biomarker concentrations and may increase operative costs, often rendering such systems inaccessible to communities in low-to-middle-income countries (LMICs). As a response, passive samplers have emerged as a way to make wastewater sampling more efficient and obtain more reliable, consistent data. Therefore, this study aims to review recent developments in passive sampling technologies to provide researchers with the tools to develop novel passive sampling strategies. Although promising advances in the development of nanostructured passive samplers have been reported, optimization remains a significant area of opportunity for researchers in the area, as methods for flexible, robust adsorption and recovery of viral genetic materials would greatly improve the efficacy of WBS systems while making them more accessible for communities worldwide.

Occurrence, transport, and detection techniques of emerging pollutants in groundwater.

Emerging pollutants (EPs) are a group of different contaminants, such as hormones, pesticides, heavy metals, and drugs, usually found in concentrations between the order of ng and µg per liter. The global population's daily city and agro-industrial activities release EPs into the environment.  Due to the chemical nature of EPs and deficient wastewater treatment and management, they are transported to superficial and groundwater through the natural water cycle, where they can potentially cause harmful effects on living organisms. Recent efforts have focused on developing technology that allows EPs quantification and monitoring in real-time and in situ. The newly developed technology aims to provide accessible groundwater management that detects and treats EPs while avoiding their contact with living beings and their toxic effects. This review presents some of the recently reported techniques that have been applied to advance the detection of EPs in groundwater and potential technologies that can be used for EP removal.

Occurrence of Z-drugs, benzodiazepines, and ketamine in wastewater in the United States and Mexico during the Covid-19 pandemic.

Z-drugs, benzodiazepines and ketamine are classes of psychotropic drugs prescribed for treating anxiety, sleep disorders and depression with known side effects including an elevated risk of addiction and substance misuse. These drugs have a strong potential for misuse, which has escalated over the years and was hypothesized here to have been exacerbated during the COVID-19 pandemic. Wastewater-based epidemiology (WBE) constitutes a fast, easy, and relatively inexpensive approach to epidemiological surveys for understanding the incidence and frequency of uses of these drugs. In this study, we analyzed wastewater (n = 376) from 50 cities across the United States and Mexico from July to October 2020 to estimate drug use rates during a pandemic event. Both time and flow proportional composite and grab samples of untreated municipal wastewater were analyzed using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry to determine loadings of alprazolam, clonazepam, diazepam, ketamine, lorazepam, nordiazepam, temazepam, zolpidem, and zaleplon in raw wastewater. Simultaneously, prescription data of the aforementioned drugs were extracted from the Medicaid database from 2019 to 2021. Results showed high detection frequencies of ketamine (90 %), lorazepam (87 %), clonazepam (76 %) and temazepam (73 %) across both Mexico and United States and comparatively lower detection frequencies for zaleplon (22 %), zolpidem (9 %), nordiazepam (<1 %), diazepam (<1 %), and alprazolam (<1 %) during the pandemic. Average mass consumption rates, estimated using WBE and reported in units of mg/day/1000 persons, ranged between 62 (temazepam) and 1100 (clonazepam) in the United States. Results obtained from the Medicaid database also showed a significant change (p < 0.05) in the prescription volume between the first quarter of 2019 (before the pandemic) and the first quarter of 2021 (pandemic event) for alprazolam, clonazepam and lorazepam. Study results include the first detections of zaleplon and zolpidem in wastewater from North America.

An opinion on Wastewater-Based Epidemiological Monitoring (WBEM) with Clinical Diagnostic Test (CDT) for detecting high-prevalence areas of community COVID-19 Infections.

Wastewater-Based Epidemiological Monitoring (WBEM) is an efficient surveillance tool during the COVID-19 pandemic as it meets all requirements of a complete monitoring system including early warning, tracking the current trend, prevalence of the disease, detection of genetic diversity as well asthe up-surging SARS-CoV-2 new variants with mutations from the wastewater samples. Subsequently, Clinical Diagnostic Test is widely acknowledged as the global gold standard method for disease monitoring, despite several drawbacks such as high diagnosis cost, reporting bias, and the difficulty of tracking asymptomatic patients (silent spreaders of the COVID-19 infection who manifest nosymptoms of the disease). In this current reviewand opinion-based study, we first propose a combined approach) for detecting COVID-19 infection in communities using wastewater and clinical sample testing, which may be feasible and effective as an emerging public health tool for the long-term nationwide surveillance system. The viral concentrations in wastewater samples can be used as indicatorsto monitor ongoing SARS-CoV-2 trends, predict asymptomatic carriers, and detect COVID-19 hotspot areas, while clinical sampleshelp in detecting mostlysymptomaticindividuals for isolating positive cases in communities and validate WBEM protocol for mass vaccination including booster doses for COVID-19.

Expanding the Scope of Nanobiocatalysis and Nanosensing: Applications of Nanomaterial Constructs.

The synergistic interaction between advanced biotechnology and nanotechnology has allowed the development of innovative nanomaterials. Those nanomaterials can conveniently act as supports for enzymes to be employed as nanobiocatalysts and nanosensing constructs. These systems generate a great capacity to improve the biocatalytic potential of enzymes by improving their stability, efficiency, and product yield, as well as facilitating their purification and reuse for various bioprocessing operating cycles. The different specific physicochemical characteristics and the supramolecular nature of the nanocarriers obtained from different economical and abundant sources have allowed the continuous development of functional nanostructures for different industries such as food and agriculture. The remarkable biotechnological potential of nanobiocatalysts and nanosensors has generated applied research and use in different areas such as biofuels, medical diagnosis, medical therapies, environmental bioremediation, and the food industry. The objective of this work is to present the different manufacturing strategies of nanomaterials with various advantages in biocatalysis and nanosensing of various compounds in the industry, providing great benefits to society and the environment.

Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions.

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.

Understanding the HPV integration and its progression to cervical cancer.

Cervical cancer is one of the main causes of female cancer death worldwide, and human papilloma virus (HPV) its causal agent. To investigate viral oncogenesis several studies have focused on the effects of HPV oncoproteins E6 and E7 and the mechanisms by which these proteins stimulate the cellular transformation process. However, phenomena such as the physical state of the viral genome (episomal or integrated) and the effects of this integration on cell proliferation contribute new clues to understand how HPV infection causes carcinogenesis. New molecular technologies are currently facilitating these discoveries. This paper reviews the tumor development process initiated by HPV, recent findings on the process of viral integration into the host genome, new methods to detect HPV integration, and derived associated effects.