Identification of Phytochemicals with Inhibitory Potential Against Beta-lactamase Enzymes via Computer-aided Approach.

INTRODUCTION: Antibacterial drugs have been widely used for the past century to treat diseases, but their efficacy has been limited by multi-resistant pathogens, particularly those that utilize beta-lactamase enzymes. The inhibition of beta-lactamase enzymes holds great promise for reducing the influence of such pathogens. OBJECTIVE: This study aims to evaluate the mechanism of inhibition of phytochemicals with antibacterial activity against two classes of beta-lactamases using computational methods. METHODS: To achieve this objective, a total of thirty phytochemicals were docked against SHV-1 beta-lactamase and AmpC beta-lactamase after procurement from Protein Data Bank. The pharmacokinetics (ADMET) and density functional theory (DFT) analysis study were also conducted to unravel the nature of the top six most promising compounds on each protein. RESULTS: The results showed that a significant percentage of the compounds had binding affinities greater than that of avibactam, the positive control. Quercetin-3-O-rutinoside showed the most promising results against SHV-1 beta-lactamase with an affinity of -9.4 kcal/mol, while luteolin was found to be the most promising candidate against AmpC beta-lactamase with an affinity of -8.5 kcal/mol. DFT analysis demonstrated the reactivity of these compounds, and the ADMET study indicated that they were relatively safe. CONCLUSION: In conclusion, the study's findings suggest that the selected compounds have significant potential to inhibit beta-lactamase and may be used in combination with antibiotics against organisms that produce beta-lactamase. This study provides a basis for further research in a wet-lab setting to validate the results.

Population-based estimates of acute gastrointestinal and foodborne illness in Barbados: a retrospective cross-sectional study.

The aim of this study was to determine the burden and impact of acute gastroenteritis (AGE) and foodborne diseases (FBDs) in Barbados through a retrospective, cross-sectional population survey and laboratory study in August 2010-August 2011. Face-to-face interviews were conducted with one person from each of 1,710 randomly-selected households. Of these, 1,433 (84%) interviews were completed. A total of 70 respondents reported having experienced AGE in the 28 days prior to the interview, representing a prevalence of 4.9% and an annual incidence rate of 0.652 episodes per person-year. Age (p = 0.01132), season (p = 0.00343), and income (p < 0.005) were statistically associated with the occurrence of AGE in the population. Norovirus was the leading foodborne pathogen causing AGE-related illness. An estimated 44,270 cases of AGE were found to occur during the period of the study and, for every case of AGE detected by surveillance, an additional 204 cases occurred in the community. Economic costs of AGE ranged from BD$ 9.5 million to 16.5 million (US$ 4.25-8.25) annually. This study demonstrated that the public-health burden and impact of AGE and FBD in Barbados were high and provided the necessary baseline information to guide targeted interventions.

Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs covalently bound topoisomerase I-DNA complexes and is essential for preventing the formation of double-strand breaks that result when stalled topoisomerase I complexes interfere with DNA replication in yeast. Here we show that a deficiency of this DNA repair pathway in humans does not predispose to neoplasia or dysfunctions in rapidly replicating tissues, but instead causes spinocerebellar ataxia with axonal neuropathy (SCAN1) by affecting large, terminally differentiated, non-dividing neuronal cells. Using genome-wide linkage mapping and a positional candidate approach in a Saudi Arabian family affected with autosomal recessive SCAN1, we identified a homozygous mutation in TDP1 (A1478G) that results in the substitution of histidine 493 with an arginine residue. The His493 residue is conserved in TDP1 across species and is located in the active site of the enzyme. Protein modeling predicts that mutation of this amino acid to arginine will disrupt the symmetric structure of the active site. We propose that loss-of-function mutations in TDP1 may cause SCAN1 either by interfering with DNA transcription or by inducing apoptosis in postmitotic neurons.

Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.

Factors Influencing the Time of Intubation Using C-MAC D-Blade® Video Laryngoscope: An Observational Cross-Sectional Study.

Purpose C-MAC D-Blade® (Karl Storz, Tuttlingen, Germany) video laryngoscope (VL) has proved to be of immense utility in difficult intubation. But unfortunately, in an urgent situation, the predictable correct curvature of the endotracheal tube for effortless intubation is not met. We hypothesized that expertise is the most important variable in intubation and that novice students will be unable to intubate if the angle of curvature is incorrect. Methods An observational cross-sectional study was planned with 30 anesthesia residents, categorized into three groups based on their expertise in laryngoscopy. Students had to intubate an airway mannequin using the C-MAC D-Blade® VL with three different stylet angulations. The curvatures were 80, 100, and 120 degrees, which are commonly encountered in routine day-to-day practice. The time to get a stable glottic view, time to intubate, and ease of intubation were measured. Results The mean time to intubate was the least with 100-degree angulation in group C (19.60 ± 0.97) while the maximum time was in group A with 80-degree angulation (61.49 ± 3.69). A significant difference was noted in time to get a stable glottic view when compared between the groups. There was no difference in time to intubate with different stylet angulations when compared between groups. Conclusions Novices and experts could intubate even if the angle of curvature was incorrect taking more time. The time to laryngoscopy is significantly dependent on experience, but the time to intubate is influenced by the angle of curvature of the stylet.

Correction: Implementation of Genomic Surveillance of SARS-CoV-2 in the Caribbean: Lessons learned for sustainability in resource-limited settings.

[This corrects the article DOI: 10.1371/journal.pgph.0001455.].

Implementation of genomic surveillance of SARS-CoV-2 in the Caribbean: Lessons learned for sustainability in resource-limited settings.

The COVID-19 pandemic highlighted the importance of global genomic surveillance to monitor the emergence and spread of SARS-CoV-2 variants and inform public health decision-making. Until December 2020 there was minimal capacity for viral genomic surveillance in most Caribbean countries. To overcome this constraint, the COVID-19: Infectious disease Molecular epidemiology for PAthogen Control & Tracking (COVID-19 IMPACT) project was implemented to establish rapid SARS-CoV-2 whole genome nanopore sequencing at The University of the West Indies (UWI) in Trinidad and Tobago (T&T) and provide needed SARS-CoV-2 sequencing services for T&T and other Caribbean Public Health Agency Member States (CMS). Using the Oxford Nanopore Technologies MinION sequencing platform and ARTIC network sequencing protocols and bioinformatics pipeline, a total of 3610 SARS-CoV-2 positive RNA samples, received from 17 CMS, were sequenced in-situ during the period December 5th 2020 to December 31st 2021. Ninety-one Pango lineages, including those of five variants of concern (VOC), were identified. Genetic analysis revealed at least 260 introductions to the CMS from other global regions. For each of the 17 CMS, the percentage of reported COVID-19 cases sequenced by the COVID-19 IMPACT laboratory ranged from 0·02% to 3·80% (median = 1·12%). Sequences submitted to GISAID by our study represented 73·3% of all SARS-CoV-2 sequences from the 17 CMS available on the database up to December 31st 2021. Increased staffing, process and infrastructural improvement over the course of the project helped reduce turnaround times for reporting to originating institutions and sequence uploads to GISAID. Insights from our genomic surveillance network in the Caribbean region directly influenced non-pharmaceutical countermeasures in the CMS countries. However, limited availability of associated surveillance and clinical data made it challenging to contextualise the observed SARS-CoV-2 diversity and evolution, highlighting the need for development of infrastructure for collecting and integrating genomic sequencing data and sample-associated metadata.

Malnutrition: An underlying health condition faced in sub Saharan Africa: Challenges and recommendations.

In Sub-Saharan Africa, the morbidity and mortality rate from malnutrition is increasing more than in any place in the world. Malnutrition has been a public health challenge in Sub-Saharan Africa that has not received enough attention. This commentary discussed the causes, effects and the need to prioritize the prevention and control of Malnutrition in Africa, together with practical recommendations. Several factors contribute to the high prevalence of malnutrition in sub-Saharan Africa. Some are poverty, overpopulation, unsuccessful small-scale agriculture, low educational status, climate change, corruption, wars and conflicts, fluctuation of food prices, etc. Conversely, the effects of malnutrition on individuals have resulted in the development of illnesses and chronic health issues. Hence, there is a need to reach out to malnourished individuals, encourage the government, investors, and non-governmental organizations (NGOs) to take action, educate health staff to detect and react to early indicators of malnutrition, enhance agricultural product output, manage and preserve the environment, and use technology to its full potential. All of these suggestions will significantly impact the incidence of malnutrition in Sub-Saharan Africa.

Strengthening Africa's capacity for vaccine research: Needs and challenges.

Vaccine development and production harbinger the control and eradication of infectious diseases. Vaccination played a huge role in the curtailment of disease outbreaks like smallpox and polio, especially in Africa. Despite the high demand for several vaccines in Africa due to the highly infectious disease burden, the continent still lacks adequate capacity for vaccine research and development. This paper aims to discuss the need and challenges of Africa to strengthen its capacity for vaccine research and development and also highlight practical recommendations. Some of the needs for Africa to prioritize vaccine research and development include; improving quality of life and well-being, cost-effectiveness, independent preparedness and response to local outbreaks, and increased access to funding. Challenges associated with vaccine research and development include the cost of the investment, risk of failure; poor ethical framework and legislation; lack of adequate funding; lack of political will & support; and poor surveillance system. Strategies to create sufficient research funds, an efficient surveillance system, and a legislative framework are clearly described. In conclusion, strengthening vaccine research capacity in Africa requires the political goodwill of African governments and strategic partnerships with international organizations and institutes. The challenges facing this development and possible solutions have been highlighted in this article.

Response to the challenges of pandemic H1N1 in a small island state: the Barbadian experience.

BACKGROUND: Having been overwhelmed by the complexity of the response needed for the severe acute respiratory syndrome (SARS) epidemic, public health professionals in the small island state of Barbados put various measures in place to improve its response in the event of a pandemic METHODS: Data for this study was collected using Barbados' National Influenza Surveillance System, which was revitalized in 2007. It is comprised of ten sentinel sites which send weekly notifications of acute respiratory illness (ARI) and severe acute respiratory illness (SARI) to the Office of the National Epidemiologist. During the 2009 H1N1 pandemic, meetings of the National Pandemic Planning Committee and the Technical Command Committee were convened. The pharmaceutical and non-pharmaceutical interventions (NPIs) implemented as a result of these meetings form the basis of the results presented in this paper. RESULTS: On June 3, 2009, Barbados reported its first case of 2009 H1N1. From June until October 2009, there were 155 laboratory confirmed cases of 2009 H1N1, with one additional case occurring in January 2010. For the outbreak period (June-October 2009), the surveillance team received reports of 2,483 ARI cases, compared to 412 cases for the same period in 2008. The total hospitalization rate due to SARIs for the year 2009 was 90.1 per 100,000 people, as compared to 7.3 per 100,000 people for 2008. Barbados' pandemic response was characterized by a strong surveillance system combining active and passive surveillance, good risk communication strategy, a strengthened public and private sector partnership, and effective regional and international collaborations. Community restriction strategies such as school and workplace closures and cancellation of group events were not utilized as public health measures to delay the spread of the virus. Some health care facilities struggled with providing adequate isolation facilities. CONCLUSIONS: The number of confirmed cases was small but the significant surge in ARI and SARI cases indicate that the impact of the virus on the island was moderate. As a result of 2009 H1N1, virological surveillance has improved significantly and local, regional and international partnerships have been strengthened.

Classification system for conventional crown and fixed partial denture failures.

The dental literature is replete with reports on the many aspects of failure encountered with traditional fixed prosthodontic treatment, including longitudinal survival studies of crowns and fixed partial dentures and reasons for failures. However, criteria for grading or classifying the type and severity of these failures are inadequate. A classification system for conventional fixed prosthodontic failures based on severity is presented.