Laminin N-terminus (LaNt) proteins, laminins and basement membrane regulation

Basement membranes (BMs) are structured regions of the extracellular matrix that provide multiple functions including physical support and acting as a barrier, as a repository for nutrients and growth factors, and as biophysical signalling hubs. At the core of all BMs is the laminin (LM) family of proteins. These large heterotrimeric glycoproteins are essential for tissue integrity, and differences between LM family members represent a key nexus in dictating context and tissue-specific functions. These variations reflect genetic diversity within the family, which allows for multiple structurally and functionally distinct heterotrimers to be produced, each with different architectures and affinities for other matrix proteins and cell surface receptors. The ratios of these LM isoforms also influence the biophysical properties of a BM owing to differences in their relative ability to form polymers or networks. Intriguingly, the LM superfamily is further diversified through the related netrin family of proteins and through alternative splicing leading to the generation of non-LM short proteins known as the laminin N-terminus (LaNt) domain proteins. Both the netrins and LaNt proteins contain structural domains involved in LM-to-LM interaction and network assembly. Emerging findings indicate that one netrin and at least one LaNt protein can potently influence the structure and function of BMs, disrupting the networks, changing physical properties, and thereby influencing tissue function. These findings are altering the way that we think about LM polymerisation and, in the case of the LaNt proteins, suggest a hitherto unappreciated form of LM self-regulation

Viral aetiology of severe acute respiratory illness among patients admitted during the 2022 peri-Hajj period

Introduction: Severe acute respiratory illness (SARI) among pilgrims continues to be an important healthcare issue. The aim of this study was to describe the viral aetiology of patients admitted to hospitals in the holy cities of Makkah and Madinah during the 2022 peri-Hajj period. Methods: This is a retrospective analysis of patients admitted to hospitals with SARI. Patients were tested with multiplex polymerase chain reaction for the most common viral aetiologies. Results: In total, 179 cases of SARI were identified during the study period. Of these, 101 (56.4%) were males, 78 (43.6%) were females, and 78 (43.6%) were Saudi. The mean age was 58.60 years (standard deviation 20.5) years. The most common age group was ≥65 years (n=68, 36%), followed by 55-59 years (n=37, 19%). The most common comorbidities were diabetes mellitus (n=67, 36%), hypertension (n=65, 35%) and chronic lung disease (n=34, 18%). Eighty-five (47.5%) patients tested negative and 94 (42.5%) tested positive for various viral aetiologies. The most frequently detected viruses were severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (n=28, 15%) and influenza (n=22, 12%); of the influenza cases, 16 were influenza A (6 (43%) were H3N2), and six were influenza B. The only case of Middle East respiratory syndrome coronavirus (MERS-CoV) was in a citizen, and none of the visitors or residents had MERS-CoV. Of the total cases, 27 (14%) died during the follow-up period. In a binary regression analysis, only age was associated with mortality (P=0.002). Conclusion: The most commonly detected viruses among patients admitted to hospital with SARI were SARS-CoV-2 and influenza. It is important to continue surveillance of admitted and non-admitted patients in different Hajj periods to identify any shift in the aetiologic agents

High seroprevalence of SARS-CoV-2 among high-density communities in Saudi Arabia

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Background: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection had been investigated utilizing serology. Materials and methods: This community-based sero-survey was carried out in the neighborhoods of three cities in Saudi Arabia. Results: Of 5629 participants, 2766 (49.1%) were women; and 2148 (38.1%) were 18-34 years of age, and 3645 (64.7%) were from South East Asia. Positive serology was seen in 2825 (50.2% (95% CI: 48.8-51.5%) for SARS-CoV-2 anti-S1 IgG antibodies by ECLIA. Being in the age category of 18-34 years and being from Eastern Mediterranean Region (country A) were associated with higher COVID-19 seropositivity with estimated odds ratio of 1.3 [95% CI 1.1-1.8] and 2.5 [95% CI 1.1.5-4.2] respectively. Gender, social status, education, nationality, symptoms, presence of comorbidities and activity style were positively associated with increased seropositivity. Factors associated negatively with the rate of seropositivity were higher education and having outdoor activity with estimated OR of 0.92 [95% CI 0.46-0.95] and 0.59 [95% CI 0.47-0.74], respectively. Conclusion: The study showed high seroprevalence of SARS-CoV-2 among high density population. Health education campaigns should target middle-aged, those with low education, those living in lower standards and indoor workers

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically