World TB Day on March 24, 2022, provided an opportunity to raise awareness of the devastating health, social, and economic impacts of tuberculosis—the world's second leading infectious killer after COVID-19—and to consider what is needed to strengthen care and control efforts to end tuberculosis. The COVID-19 pandemic has reversed years of progress in reducing the global burden of tuberculosis, with case notifications falling substantially and mortality increasing for the first time in over a decade.

A multipronged approach has been developed for the treatment of COVID-19 disease: antivirals and antibody therapy are effective during early infection when the SARS-CoV-2 load is high, whereas systemic steroids and cytokine blockade are best for the late inflammatory phase1–3 (figure). In human challenge studies of respiratory syncytial virus infection, the pre-existing so-called immunological tone of the respiratory mucosa is crucial to the receptiveness of the mucosa to viral infection.4 However, so far, in SARS-CoV-2 infection, there has been little focus on altering the condition of the respiratory mucosa.

Tuberculosis is a syndemic. Elimination requires a syndemic approach that addresses the individual and societal vulnerabilities that determine whether we become infected, get sick, die, or get better with disability and an impact on livelihoods.1 The WHO End TB Strategy, a global initiative launched in 2015, signifies that syndemic approach. End TB outlines fundamentals required to modify determinants of ill health, promote prevention of disease and early diagnosis with prompt treatment to save lives, prevent economic hardships, and reduce transmission.

The world is still grappling with the devastating effects of COVID-19 more than 2 years into the pandemic. Countries with high COVID-19 vaccination rates are transitioning to the new normal of living with SARS-CoV-2, but low-income and middle-income countries (LMICs) are struggling to vaccinate their populations while concurrently fighting other communicable diseases, key among them tuberculosis. The burden of tuberculosis, the leading cause of death from an infectious disease before COVID-19 emerged, has been deeply affected by the pandemic.

Globally, tuberculosis remains a leading cause of death from an infectious disease.1 2022's theme for World TB Day, on March 24, is “Invest to End TB. Save Lives”. Tuberculosis control requires a pragmatic, tailored, multipronged approach to diagnose and treat all people with tuberculosis disease (drug-susceptible, drug-resistant, multidrug-resistant, and extensively drug-resistant tuberculosis) and latent tuberculosis infection, to prevent transmission, and to mitigate the risk of drug resistance.

Over the past two decades, more than 66 million lives have been saved through global efforts to curb the tuberculosis pandemic.1 With intensified efforts to improve active case finding and enable prompt diagnosis and early treatment initiation, we can expect this number to increase over the next few years. As we commemorate World TB Day on March 24, 2022, nearly 3000 children worldwide still contract this preventable disease every day.

The global burden of tuberculosis disease remains stubbornly high. Population surveys estimate that 14 million individuals have prevalent disease, reflecting around 10 million incident cases per year, of which around six million are diagnosed and treated. Finding the remaining, missing millions—closing the gap between estimated number of individuals with tuberculosis disease and the number receiving care—is a key component of global and national tuberculosis care and prevention policies.1 However, such policies assume that we actually know the full burden of tuberculosis disease, which is almost certainly untrue.

Pneumonia remains the leading cause of infectious morbidity and mortality in children; however, research remains chronically under-funded and has been excluded from major global financing mechanisms.1 To achieve the Sustainable Development Goals, as set out in the UN 2030 Agenda for Sustainable Development, funding for childhood pneumonia research should be prioritised.

Jie Li and colleagues1 examined the efficacy of awake prone positioning on patients with COVID-19-related acute hypoxaemic respiratory failure. However, we have serious concerns about the assessment of the risk of bias, the data analysis, and the rating of certainty of evidence in the two cluster randomised controlled trials (RCTs) and eight individual RCTs that were included in the study.

We read the comments from Qinyuan Li and colleagues on our published systematic review and meta-analysis on awake prone positioning in patients with COVID-19-related acute hypoxaemic respiratory failure.1 We appreciate their interest in our study, and welcome the opportunity to further explain some of the finer details of our study.

In their Series paper in The Lancet Respiratory Medicine, Dheda and colleagues1 reported a discrepancy between expected and reported tuberculosis cases during the COVID-19 pandemic. We write from the Philippines, the fourth largest contributor to the number of tuberculosis cases worldwide, with 500 people affected per 100 000.2 Despite plans to improve tuberculosis programmes, aggregate tuberculosis notification decreased by 78·7% following community quarantine implementation.1,3 Multiple factors, including public perceptions about respiratory illnesses, limited health-care access, and a decentralised COVID-19 response, hindered progress for tuberculosis during the pandemic in the Philippines.

A study of nine patients with persisting SARS-CoV-2 infection during the COVID-19 pandemic revealed the emergence of several mutations associated with the alpha (lineage B.1.1.7) and beta (B.1.351) variants.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

by Nina Elisabeth Diana, Malcolm Davies, Pulane Mosiane, Alda Vermeulen, Saraladevi Naicker

The spectrum of HIV-associated kidney disease has expanded significantly with the introduction of antiretroviral therapy (ART). In the pre-ART era there was prominence of HIV-associated nephropathy (HIVAN). More recently, the spectrum of disease additionally reflects comorbid illness in the ageing HIV population and ART-related nephrotoxicity. We performed a clinicopathological correlation of kidney disease in HIV-positive individuals who underwent kidney biopsy between 1989 and 2014, utilizing the 2018 Kidney Disease Improving Global Outcomes pathologic classification. ART rollout began in 2004 in South Africa. Patients biopsied pre-ART rollout were compared to those biopsied post-ART rollout with respect to demographics, clinical parameters and histology. We assessed kidney survival in a cohort of these patients following biopsy. Six hundred and ninety biopsies were included, 99 (14.3%) were undertaken pre- and 591 (85.7%) post-ART rollout. Most patients were of Black African descent (97.5%). The post-ART rollout patients were older (p = 0.007), had higher eGFR at presentation (p = 0.016) and fewer presented with eGFR of less than 15ml/min/1.73m2 (p = 0.0008). There was a decrease in the prevalence of classic HIVAN (p = 0.00001); and an increase in FSGS (NOS) in the setting of HIV (p = 0.0022) and tubulointerstitial diseases (p = 0.009) post-ART rollout. Kidney function survival over 5 years was poorest in patients with classic HIVAN (p = 0.00005) and best in minimal change nephropathy (p = 0.0013). Kidney biopsy is crucial for the correct diagnosis and management of HIV-related kidney disease. ART rollout has shifted the spectrum of kidney disease away from classic HIVAN but has not eliminated it. Histological diagnosis prognosticates kidney survival.

by Raoul Kenfack-Momo, Sebastien Kenmoe, Guy Roussel Takuissu, Jean Thierry Ebogo-Belobo, Cyprien Kengne-Ndé, Donatien Serge Mbaga, Serges Tchatchouang, Martin Gael Oyono, Josiane Kenfack-Zanguim, Robertine Lontuo Fogang, Chris Andre Mbongue Mikangue, Elisabeth Zeuko’o Menkem, Juliette Laure Ndzie Ondigui, Ginette Irma Kame-Ngasse, Jeannette Nina Magoudjou-Pekam, Jean Bosco Taya-Fokou, Arnol Bowo-Ngandji, Seraphine Nkie Esemu, Diane Kamdem Thiomo, Paul Moundipa Fewou, Lucy Ndip, Richard Njouom

Introduction Due to their common routes of transmission, human immunodeficiency virus (HIV) coinfection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) has become a major public health problem worldwide, particularly in Africa, where these viruses are endemic. Few systematic reviews report the epidemiological data of HBV and/or HCV coinfection with HIV in Africa, and none provided data on the case fatality rate (CFR) associated with this coinfection. This study was conducted to investigate the prevalence and case fatality rate of HBV and/or HCV infections among people living with human immunodeficiency virus (PLHIV) in Africa. Methods We conducted a systematic review of published articles in PubMed, Web of Science, African Journal Online, and African Index Medicus up to January 2022. Manual searches of references from retrieved articles and grey literature were also performed. The meta-analysis was performed using a random-effects model. Sources of heterogeneity were investigated using subgroup analysis, while funnel plots and Egger tests were performed to assess publication bias. Results Of the 4388 articles retrieved from the databases, 314 studies met all the inclusion criteria. The overall HBV case fatality rate estimate was 4.4% (95% CI; 0.7–10.3). The overall seroprevalences of HBV infection, HCV infection, and HBV/HCV coinfection in PLHIV were 10.5% [95% CI = 9.6–11.3], 5.4% [95% CI = 4.6–6.2], and 0.7% [95% CI = 0.3–1.0], respectively. The pooled seroprevalences of current HBsAg, current HBeAg, and acute HBV infection among PLHIV were 10.7% [95% CI = 9.8–11.6], 7.0% [95% CI = 4.7–9.7], and 3.6% [95% CI = 0.0–11.0], respectively. Based on HBV-DNA and HCV-RNA detection, the seroprevalences of HBV and HCV infection in PLHIV were 17.1% [95% CI = 11.5–23.7] and 2.5% [95% CI = 0.9–4.6], respectively. Subgroup analysis showed substantial heterogeneity. Conclusions In Africa, the prevalence of hepatotropic viruses, particularly HBV and HCV, is high in PLHIV, which increases the case fatality rate. African public health programs should emphasize the need to apply and comply with WHO guidelines on viral hepatitis screening and treatment in HIV-coinfected patients. Review registration PROSPERO, CRD42021237795.…

by Luhong Wang, Yinan Ding, Chuanyong Zhang, Rong Chen

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease (COVID-19), which poses a major threat to humans worldwide. With the continuous progress of the pandemic, a growing number of people are infected with SARS-CoV-2, including hepatocellular carcinoma (HCC) patients. However, the relationship between COVID-19 and HCC has not been fully elucidated. In order to provide better treatment for HCC patients infected with SARS-CoV-2, it’s urgently needed to identify common targets and find effective drugs for both. In our study, transcriptomic analysis was performed on both selected lung epithelial cell datasets of COVID-19 patients and the datasets of HCC patients to identify the synergistic effect of COVID-19 in HCC patients. What’s more, common differentially expressed genes were identified, and a protein-protein interactions network was designed. Then, hub genes and basic modules were detected based on the protein-protein interactions network. Next, functional analysis was performed using gene ontology terminology and the Kyoto Encyclopedia of Genes and Genomes pathway. Finally, protein-protein interactions revealed COVID-19 interaction with key proteins associated with HCC and further identified transcription factor (TF) genes and microRNAs (miRNA) with differentially expressed gene interactions and transcription factor activity. This study reveals that COVID-19 and HCC are closely linked at the molecular level and proposes drugs that may play an important role in HCC patients with COVID-19. More importantly, according to the results of our research, two critical drugs, Ilomastat and Palmatine, may be effective for HCC patients with COVID-19, which provides clinicians with a novel therapeutic idea when facing possible complications in HCC patients with COVID-19.

by Manachai Yingklang, Apisit Chaidee, Rungtiwa Dangtakot, Chanakan Jantawong, Ornuma Haonon, Chutima Sitthirach, Nguyen Thi Hai, Ubon Cha’on, Sirirat Anutrakulchai, Supot Kamsa-ard, Somchai Pinlaor

Background Several studies have demonstrated that helminth infections provide a degree of protection against Type 2 diabetes mellitus (T2DM). However, the relationship between Strongyloides stercoralis infection and T2DM has scarcely been investigated and the protective effect of infection against development of diabetic complications is unclear. In this study, we aimed to investigate the relationship between S. stercoralis infection and T2DM in a rural area of Khon Kaen Province, Thailand. The impact of S. stercoralis infection on diabetic complication-related kidney function biochemical parameters and body-mass index (BMI) was also assessed. Methodology Using a cross-sectional study design, S. stercoralis infection and T2DM assessments were conducted between October 2020 and May 2021. Associations between S. stercoralis infection, T2DM, and socioeconomic factors were analyzed using multivariable logistic regression analyses. Diabetic complication-related biochemical parameters relating largely to kidney function (estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), serum creatinine, uric acid, alanine transaminase (ALT), and low-density lipoprotein cholesterol (LDL-C)) and BMI of participants with and without T2DM were compared between groups with or without S. stercoralis infection. Results One hundred and seven out of 704 individuals (15.20%) were positive for S. stercoralis, and 283 people were diagnosed with T2DM. Of those with T2DM, 11.31% (32/283) were infected with S. stercoralis and of those without T2DM, 17.82% (75/421) were infected with S. stercoralis. Multivariate analysis revealed that T2DM was inversely correlated with S. stercoralis infection (Adjusted OR  =  0.49; 95% CI: 0.30, 0.78; p  = 0.003), while male, increasing age, lower education level, and alcohol intake were positively associated with infection. Those infected with S. stercoralis had lower eGFR levels and higher ALT and UACR levels than those in the uninfected group. Conclusion This finding indicates that S. stercoralis infection was inversely associated with T2DM in northeastern Thailand, but participants infected with S. stercoralis had lower eGFR levels and higher ALT and UACR levels. Infection with S. stercoralis might lead to worse complication-related renal biochemical parameters.…

by Ibrahim Khater, Aaya Nassar

COVID-19 outbreak associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) raised health concerns across the globe and has been considered highly transmissible between people. In attempts for finding therapeutic treatment for the new disease, this work has focused on examining the polymerase inhibitors against the SARS-CoV-2 nsp12 and co-factors nsp8 and nsp7. Several polymerase inhibitors were examined against PDB ID: 6M71 using computational analysis evaluating the ligand’s binding affinity to replicating groove to the active site. The findings of this analysis showed Cytarabine of -5.65 Kcal/mol with the highest binding probability (70%) to replicating groove of 6M71. The complex stability was then examined over 19 ns molecular dynamics simulation suggesting that Cytarabine might be possible potent inhibitor for the SARS-CoV-2 RNA Dependent RNA Polymerase.

by Lenore D. Pitstick, Joanna Goral, Ryan A. Schmelter, Christine M. Fuja, Mae J. Ciancio, Matthew Pytynia, Alice Meyer, Jacalyn M. Green

Risk factors for liver cancer include tobacco use, alcohol consumption, obesity, and male sex. Administration of 4-nitroquinonline-1-oxide (4NQO) in drinking water mimics the effects of tobacco and leads to oral carcinoma in mice. This study compared the effects of diets high and low in saturated fat (HF and LF, respectively), and sex, on liver histopathology in 4NQO-treated mice and controls. We hypothesized that 4NQO would cause histopathological changes in liver, and that a HF diet would increase hepatic pathology when compared to the LF diet. Mice (C57Bl/6, 36/sex), were divided into a low fat (10 kcal% fat; LF) or high fat (60 kcal% fat, HF) diet. Mice were further subdivided into one of 3 water treatment groups for 17 weeks: water (control), vehicle (1.25% propylene glycol in water [PG]), or 4NQO in (50 μg/ml; 4NQO). All mice were subsequently given water alone for 6 more weeks. Upon euthanasia, livers were harvested, fixed, sectioned, and stained with hematoxylin and eosin (H&E). H&E slides were graded for histopathology; frozen liver samples were analyzed for triglyceride content. Trichrome stained sections were graded for fibrosis. CD3+ T cells, CD68+ macrophages, and Ly6+ neutrophils were detected by immunohistochemistry. Compared to water controls, 4NQO-treatment caused mouse liver histopathological changes such as fibrosis, and increases in hepatic neutrophils, T cells, and macrophages. HF diet exacerbated pathological changes compared to LF diet. Male controls, but not females, demonstrated severe steatosis and increased triglyceride content. 4NQO treatment decreased hepatic fat accumulation, even in animals on a HF diet. In conclusion, this murine model of oral cancer may serve as a model to study the effects of tobacco and diet on liver.

by Baihan Lin, Djallel Bouneffouf, Guillermo Cecchi

Unlike traditional time series, the action sequences of human decision making usually involve many cognitive processes such as beliefs, desires, intentions, and theory of mind, i.e., what others are thinking. This makes predicting human decision-making challenging to be treated agnostically to the underlying psychological mechanisms. We propose here to use a recurrent neural network architecture based on long short-term memory networks (LSTM) to predict the time series of the actions taken by human subjects engaged in gaming activity, the first application of such methods in this research domain. In this study, we collate the human data from 8 published literature of the Iterated Prisoner’s Dilemma comprising 168,386 individual decisions and post-process them into 8,257 behavioral trajectories of 9 actions each for both players. Similarly, we collate 617 trajectories of 95 actions from 10 different published studies of Iowa Gambling Task experiments with healthy human subjects. We train our prediction networks on the behavioral data and demonstrate a clear advantage over the state-of-the-art methods in predicting human decision-making trajectories in both the single-agent scenario of the Iowa Gambling Task and the multi-agent scenario of the Iterated Prisoner’s Dilemma. Moreover, we observe that the weights of the LSTM networks modeling the top performers tend to have a wider distribution compared to poor performers, as well as a larger bias, which suggest possible interpretations for the distribution of strategies adopted by each group.

by Chen-Xiang Wei, Ju-Hua Wu, Yue-Hong Huang, Xiao-Zhong Wang, Jian-Ying Li

Lactobacillus plantarum (LP) has been shown to exhibit protective effects on intestinal barrier function in septic rats, although the regulatory mechanism has not been established. We determined whether LP imparts such protective effects in a lipopolysaccharide (LPS)-induced Caco2 cell monolayer model and whether cAMP-PKA signaling is the underlying mechanism of action. The cyclic adenosine monophosphate (cAMP) agonist, forskolin (FSK), and the protein kinase A (PKA) inhibitor, HT89, were used to study the protective effect of LP on the destruction of the tight junction (TJ) structure of cells treated with LPS and the corresponding changes in cAMP-PKA signaling. Our experimental results demonstrated that LP promoted the expression of TJ proteins between Caco2 cells after LPS treatment, and increased the electrical barrier detection (TEER) between Caco2 cells. Moreover, transmission electron microscopy (TEM) revealed that the TJ structural integrity of cells treated with LPS + LP was improved compared to cells treated with LPS alone. In addition, our findings were consistent between the FSK and LP intervention group, while HT89 inhibited LP influence. Taken together, our results indicate that LP has an improved protective effect on LPS-induced damage to the monolayer membrane barrier function of Caco2 cells and is regulated by the cAMP-PKA pathway.

Abstract

There are increasing reports of the Asian malaria mosquito, Anopheles stephensi invading and spreading in Eastern Africa. We discuss the importance of these invasions in the context of broader challenges facing malaria control in Africa and argue against addressing it as an isolated problem. Anopheles stephensi is only one of multiple biological threats facing malaria control in the region—and is itself an indication of wide-ranging weaknesses in vector surveillance and control programs. Expanded investigations are needed in both urban and rural areas, especially in countries serviced by the Indian Ocean trade routes, to establish the full extent and future trajectories of the problem. More importantly, instead of tackling this vector species as a stand-alone threat, affected countries should adopt more integrated and multi-sectorial initiatives that can sustainably drive and keep out malaria.…

Abstract

Background

In Brazil, malaria is caused mainly by the Plasmodium vivax and Plasmodium falciparum species. Its transmission occurs in endemic and non-endemic areas. Malaria geography in Brazil has retracted and is now concentrated in the North region. The Brazilian Amazon region accounts for 99% of Brazil's cases. Brazil’s extra-Amazon region has a high frequency of imported cases and in 2019 presented a mortality rate 123 times higher than the Amazon region. Extra-Amazon cases present risks of reintroduction. This study aims to characterize the epidemiological scenario for malaria in the extra-Amazon region of Brazil from 2011 to 2020 with a two-year forecast.

Methods

Time-series study with description of malaria cases and deaths registered in Brazilian extra-Amazon region from 2011 to 2020. Public data from the Notifiable Diseases Information System (Sinan) and the Mortality Information System (SIM) were used. Descriptive analysis, incidence, and notification rates were calculated. Flow charts analysed the flux between Places of Probable Infection (PI) and places of notification. The prediction model utilized a multiplicative Holt-winters model for trend and seasonality components.

Results

A total of 6849 cases were registered. Cases were predominantly white males with 9 to 11 years of education, mostly between 30 and 39 years old. Imported cases accounted for 78.9% of cases. Most frequent occupations for imported cases are related to travelling and tourism activities. Among autochthonous cases, there is a higher frequency of agriculture and domestic economic activities. In the period there were 118 deaths due to malaria, of which 34.7% were caused by P. falciparum infections and 48.3% were not specified. The most intense flows of imported cases are from Amazonas and Rondônia to São Paulo, Rio de Janeiro, and Paraná. The prediction estimates around 611 cases for each of the following two years.

Conclusion

The time series allows a vast epidemiological visualization with a short-term prediction analysis that supports public health planning. Government actions need to be better directed in the extra-Amazon region so the objective of eliminating malaria in Brazil is achieved. Carrying out quality assessments for information systems and qualifying personnel is advisable. Malaria outside the Amazon region is mainly due to imported cases and delay in diagnosis is associated with a higher fatality rate. Better strategies to diagnose and treat suspected cases can lead to lower risk of deaths and local outbreaks that will be important for achieving malaria elimination in Brazil.

…

AbstractThe microbial world represents a phenomenal diversity of microorganisms from different kingdoms of life which occupy an impressive set of ecological niches. Most, if not all, microorganisms once colonise a surface develop architecturally complex surface-adhered communities which we refer to as biofilms. They are embedded in polymeric structural scaffolds serve as a dynamic milieu for intercellular communication through physical and chemical signalling. Deciphering microbial ecology of biofilms in various natural or engineered settings has revealed co-existence of microorganisms from all domains of life, including Bacteria, Archaea and Eukarya. The coexistence of these dynamic microbes is not arbitrary, as a highly coordinated architectural setup and physiological complexity show ecological interdependence and myriads of underlying interactions.In this review, we describe how species from different kingdoms interact in biofilms and discuss the functional consequences of such interactions. We highlight metabolic advances of collaboration among species from different kingdoms, and advocate that these interactions are of great importance and need to be addressed in future research. Since trans-kingdom biofilms impact diverse contexts, ranging from complicated infections to efficient growth of plants, future knowledge within this field will be beneficial for medical microbiology, biotechnology, and our general understanding of microbial life in nature.

AbstractFungi are well-known decomposers of organic matter that thrive in virtually any environment on earth where they encounter wealths of other microbes. Some fungi evolved symbiotic lifestyles, including pathogens and mutualists, that have mostly been studied in binary interactions with their hosts. However, we now appreciate that such interactions are greatly influenced by the ecological context in which they take place. While establishing their symbioses, fungi not only interact with their hosts, but also with the host-associated microbiota. Thus, they target the host and its associated microbiota as a single holobiont. Recent studies have shown that fungal pathogens manipulate the host microbiota by means of secreted effector proteins with selective antimicrobial activity to stimulate disease development. In this review we discuss the ecological contexts in which such effector-mediated microbiota manipulation is relevant for the fungal lifestyle and argue that this is not only relevant for pathogens of plants and animals, but beneficial in virtually any niche where fungi occur. Moreover, we reason that effector-mediated microbiota manipulation likely evolved already in fungal ancestors that encountered microbial competition long before symbiosis with land plants and mammalian animals evolved. Thus, we claim that effector-mediated microbiota manipulation is fundamental to fungal biology.

Abstract

Background

An increasing number of patients are being prescribed anticoagulants and platelet inhibitors (antithrombotic treatment). Basic research has suggested an association between antithrombotic treatment and bacteremia during kidney infection. Here, we investigated the association between antithrombotic treatment, bacteremia and acute kidney injury in patients with acute pyelonephritis.

Methods

A retrospective cohort study was conducted in a large university hospital in Sweden. Data were retrieved from electronic medical records for adult patients with acute pyelonephritis in 2016. The main outcome was bacteremia and secondary outcome acute kidney injury. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated through multiple logistic regression. Treatment with different groups of antithrombotic agents were compared to no antithrombotic treatment.

Results

1814 patients with acute pyelonephritis were included, in whom bacteremia developed in 336 (18.5%). Low-molecular-weight heparin (LMWH) at prophylactic doses was associated with a lower risk of bacteremia, compared to no antithrombotic treatment (OR 0.5; 95% CI 0.3–0.7). Other antithrombotic treatments were not associated with a risk of bacteremia. Additionally, patients with prophylactic doses of LMWH had a lower risk of acute kidney injury (OR 0.5; 95% CI 0.3–0.8).

Conclusions

We found no association between antithrombotic treatment and an increased risk of bacteremia during acute pyelonephritis. Conversely, patients with prophylactic doses of LMWH had a slightly reduced risk of bacteremia. LMWH at prophylactic doses was also associated with a lower risk of acute kidney injury. Our results suggest that it is safe to continue antithrombotic treatment during acute pyelonephritis, in regards to bacteremia and acute kidney injury risk.

…

Podocalyxin (PODXL), a cell surface sialomucin expressed in diverse types of normal and malignant cells, mediates cellular adhesion to extracellular matrix and cell-to-cell interaction. A previous study reported the expression of PODXL protein on monocytes undergoing macrophage differentiation, yet the expression of this molecule in other antigen presenting cells (APCs) and its function in the immune system still remain undetermined. In this study, we report that PODXL is expressed in human monocyte-derived immature dendritic cells at both the mRNA and protein levels. Following dendritric cells maturation using pro-inflammatory stimuli, PODXL expression level decreased substantially. Furthermore, we found that PODXL expression is positively regulated by IL-4 through MEK/ERK and JAK3/STAT6 signaling pathways. Our results revealed a polarized distribution of PODXL during the interaction of APCs with CD4+ T cells, partially colocalizing with F-actin. Notably, PODXL overexpression in APCs promoted their interaction with CD4+ T cells and CD8+ T cells and decreased the expression of MHC-I, MHC-II, and the costimulatory molecule CD86. In addition, PODXL reduced the translocation of CD4+ T-cell centrosome toward the APC-contact site. These findings suggest a regulatory role for PODXL expressed by APCs in immune responses, thus representing a potential target for therapeutic blockade in infection and cancer.…

Nature Reviews Microbiology, Published online: 31 May 2022; doi:10.1038/s41579-022-00745-6Trace metals are essential micronutrients required for survival across all kingdoms of life. In this Review, Murdoch and Skaar discuss the strategies whereby vertebrate hosts limit metal or induce excess metal to prevent bacterial proliferation, a process termed nutritional immunity, and they discuss adaptive mechanisms that bacterial pathogens have evolved to survive in conditions of metal depletion or excess.

Nature Medicine, Published online: 31 May 2022; doi:10.1038/s41591-022-01824-0The elimination of malaria from China relied on local decision-makers who tested and implemented interventions, combined with a centralized drug discovery program. This holds lessons for other malaria-endemic countries.