Effective Enteral Treatment of Antibiotic for Patient with Respiratory Failure and Septic Shock in the Intensive Care Unit

Background: Pneumonia is a lung infection involving pulmonary alveoli caused by microbes, including bacteria, viruses, and fungi. It is a major infection that causes hospitalization and death worldwide and exacts an enormous cost in economic and human terms. The study to assess clinical outcomes for a critically ill patient treated with an enteral antibiotic for bacterial pneumonia is still limited. Case: We reported a case of pneumonia from 68 years old patient that caused respiratory failure and septic shock in the intensive care unit treated by enteral antibiotic and had a good outcome. Conclusion: Pneumonia can cause respiratory failure and septic conditions. Optimum antibiotic management is one of the methods to solve this problem. The benefit of utilizing enteral antibiotics is substantial and probably appropriate in certain patients.

Reversed-engineered human alveolar lung-on-a-chip model

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.

Favorable Prognostics of Post-Exercise Irisine Released as Prophylaxis of Serious Covid-19 in Obese Elderly

Studies sought epidemiological profiles to establish risk groups for Covid-19’s evolution and discovered that the age group above 65 years old is one of the most severely affected, due to the presence of other comorbidities. In the USA approximately 55 million individuals are above that age range and more than 23 million are elderly obese individuals, alongside the high mortality rate in this population and lack of proven effective medicine against Covid-19, therapeutic alternatives against this disease are sought. With the occurrence of inflammatory pulmonary conditions increased by SARS-Cov-2 infection, irisin was indicated as having a potential preventive action. This peptide is secreted endogenously by striated skeletal muscles with fibronectin type III domain-containing protein 5 (FNDC5) proteolysis, when preceded by continued exercise of low to moderate intensity for more than 20 uninterrupted minutes. Regarding the weight variant, previous studies showed low levels of FNDC5 in people with excess fatty acids (in humans, adipose tissue divides into white, favoring the deposit of lipids, triglycerides and fat, more easily inflamed, and brown that stimulates thermogenesis). Among other functions, FNDC5 also stimulates the coactivator 1-alpha of PPAR gamma (PGC-1α) which corroborates with the uncoupling between the Uncoupling Protein 1 (UCP1) and the mitochondria. When UCP1 is disincorporated from this organelle, it becomes active and inhibits ATP synthesis, releasing heat, as well as favoring fatty acid oxidation and provides the mechanism of browning of white fat. After this conversion, irisin reduces ¼ of lipid accumulation present in the adipocyte by lipolysis, significantly increasing the levels of serum triglycerides and glycerols, as well as considerably reducing oxidative stress and DNA damage. Other genes expressed by irisin also assist in the fat browning process, such as TMEM26, ELOVL3, CIDEa and COX7a. Regarding the age variant, the SARS-CoV-2 Spike protein benefits from the high concentration of angiotensin-converting enzyme 2 (ACE2) receptors, present in elderly pulmonary alveoli, which bind to the airway and enable contagion. However, ACE2 is negatively regulated by Tribbles homolog 3 (TRIB3) protein from its connection to the nucleocapsid protein of the virus, generating some protection for the individual when TRIB3 is at satisfactory levels. In elderly men, this protein is below normal levels, making this population more vulnerable to SARS-CoV-2 infection. Moreover, it was verified that irisin’s weekly synthesis promoted by regular physical exercises triples TRIB3 levels in pulmonary alveoli. In short, this hormone was able to negatively modulate two important risk factors related to the inflammatory profile of this elderly population (weight and age), and thus irisin should be considered a potential molecule in the prevention against Covid-19.

Le rôle climatique des fronts océaniques de fine échelle en profondeur (prix Prud'homme 2020)

L'océan est le plus grand réservoir d'énergie de notre planète. La quantité de chaleur qu'il est capable de stocker est modulée par sa circulation complexe, opérant sur des échelles allant du centimètre à la dizaine de milliers de kilomètres. Les découvertes scientifiques des deux dernières décennies ont révélé l'existence de fronts de fine échelle (d'environ 1 à 50 km), analogues aux fronts atmosphériques, dans la couche de mélange océanique de surface. Ces fronts agissent comme des conduits entre l'océan et l'atmosphère, contrôlant les échanges de gaz et de chaleur. Combinant observation et modélisation, nous démontrons pour la première fois le rôle capital de ces fronts jusqu'à 1000 m de profondeur. Ils génèrent d'importants flux de chaleur dirigés de l'intérieur de l'océan vers la surface, pouvant modifier la capacité de stockage de chaleur de l'océan, avec des répercussions potentiellement majeures pour les systèmes biogéochimique et climatique. The ocean is the largest solar energy collector on Earth. The amount of heat it can store is modulated by its complex circulation, which spans a broad range of spatial scales, from centimeters to thousands of kilometers. Scientific discoveries of the past two decades revealed the existence of fine-scale fronts (≈ 10-20 km wide), analogous to atmospheric fronts, in the oceanic surface mixed layer. These fronts control the exchanges between the ocean and the atmosphere just as the capillary vessels of our pulmonary alveoli facilitate the exchange of gas when breathing. Combining observation and modeling, we demonstrate for the first time the crucial role played by these fronts in the ocean interior. These fine-scale fronts drive an anomalous upward heat transport from the ocean interior back to the surface. This can alter the ocean heat storage capacity, with potential major implications for the biogeochemical and climate systems.

Analysis of the area and the number of pulmonary alveoli through the normal aging process in CD1 mouse

During the aging process, the lung exhibits structural changes accompanied by a decline in its function. The related information currently available is still scarce and contradictory. In addition, changes in some pulmonary parameters through aging process are species- and strain- dependent. The aim of this study was the assessment of the area and the number of pulmonary alveoli through the normal aging process in CD1 mouse. Paraffin-embedded sections of lungs from CD1 mice at age of 2, 6, 12, 18, or 24 months were stained with hematoxylin and eosin and examined using a light microscope. Images were captured using a camera linked to an image analysis software to measure areas and count alveoli. There was a significant difference in the alveolar area among the ages analyzed (F=87.53, Sig.=0.000). The alveolar area of the 6-, 12-, 18-, and 24-month-old mice was significantly greater (all p values < 0.001) than in mice at 2 months of age. Also, the alveolar number was significantly different among the ages tested (F=3.21, Sig.=0.023). The number of alveoli in mice at 2 months of age was greater than in mice at all other age groups, reaching statistical significance when compared with the 6-, 12-, and 18-month-old mice ( p values of 0.044, 0.014, and 0.002, respectively). Thus, we observed an increase in alveolar area and a decrease in alveolar number through the aging process. This information might be useful to understand pathologic changes underlying susceptibility of elderly individuals to chronic lower respiratory tract diseases.

The Vital Lung Capacity of Employees with Risk Factors for Potential Exposure to Ammonia Gas

The fertilizer industry produces several pollutants such as ammonia gas, urea dust, smoke, particulates. Workers are exposed to air inhalation at work, entering the respiratory system, which is the main toxic entry point. The risk of workers being exposed to lung disease due to inhalation of dust/ smoke/ harmful gases in the work environment. It will increase if workers do not comply with protecting themselves from risk factors and potential accompanying factors such as smoking habits excessive body mass index. Lung ventilation is the entry and exit of air between the atmosphere and the pulmonary alveoli. This study aimed to determine the correlation between body mass index, smoking habits, and hemoglobin levels with vital lung capacity to P.T. Pupuk Sriwidjaja Palembang employees. The design of this study is a cross-section. The research was conducted at P.T. Pupuk Sriwidjaja for 30 days. The research sample was 78 employees of the ammonia unit. Data analysis found a significant correlation between vital lung capacity with body mass index (p-value = 0.009), and hemoglobin levels (p-value = 0.039). There was no significant correlation between smoking habits and vital lung capacity values (p-value = 0.449). It can be concluded that body mass index, smoking habits, and hemoglobin levels correlate with vital lung capacity.

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract

BackgroundZoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors.Materials and methodsWe systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19.FindingsOur results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19.Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19.InterpretationThese results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.Research in contextEvidence before this studyPrevious studies of ACE2 mRNA transcript abundance in the human respiratory tract have suggested a possible association between ACE2 expression and age, sex, and the presence of comorbidities. However, these studies have provided conflicting results, as well as a lack of protein validation. Previous ACE2 protein studies have been limited by a paucity of lung tissue samples and reports that have produced contradictory results.Added value of this studyUsing a combination of single-cell RNA sequencing and immunohistochemistry, we describe ACE2 expression in the human respiratory tract. Staining protocols were optimized and validated to show consistent apical localization and avoid non-specific staining. We show ACE2 protein is found in subsets of airway cells and is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development for COVID-19, respectively. We show age, sex, and comorbidities do not increase ACE2 protein expression in the human respiratory tract.Implications of all the available evidenceACE2 protein abundance does not correlate with risk factors for severe clinical outcomes, but in some cases showed an inversed relationship. Features driving COVID-19 susceptibility and severity are complex, our data suggests factors other than ACE2 protein abundance as important determinants of clinical outcomes.

New Insight into the Development of the Respiratory Acini in Rabbits: Morphological, Electron Microscopic Studies, and TUNEL Assay

This study investigated the histomorphological features of developing rabbit respiratory acini during the postnatal period. On the 1st day of postnatal life, the epithelium of terminal bronchiole consisted of clear cells which intercalated between few ciliated and abundant non-ciliated (Clara) cells. At this age, the rabbit lung was in the alveolar stage. The terminal bronchioles branched into several alveolar ducts, which opened into atria that communicated to alveolar sacs. All primary and secondary inter-alveolar septa were thick and showed a double-capillary network (immature septa). The primitive alveoli were lined largely by type-I pneumocytes and mature type-II pneumocytes. The type-I pneumocytes displayed an intimate contact with the endothelial cells of the blood capillaries forming the blood–air barrier (0.90 ± 0.03 µm in thickness). On the 3rd day, we observed intense septation and massive formation of new secondary septa giving the alveolar sac a crenate appearance. The mean thickness of the air–blood barrier decreased to reach 0.78 ± 0.14 µm. On the 7th day, the terminal bronchiole epithelium consisted of ciliated and non-ciliated cells. The non-ciliated cells could be identified as Clara cells and serous cells. New secondary septa were formed, meanwhile the inter-alveolar septa become much thinner and the air–blood barrier thickness was 0.66 ± 0.03 µm. On the 14th day, the terminal bronchiole expanded markedly and the pulmonary alveoli were thin-walled. Inter-alveolar septa become much thinner and single capillary layers were observed. In the 1st month, the secondary septa increased in length forming mature cup-shaped alveoli. In the 2nd month, the lung tissue grew massively to involve the terminal respiratory unit. In the 3rd month, the pulmonary parenchyma appeared morphologically mature. All inter-alveolar septa showed a single-capillary layer, and primordia of new septa were also observed. The thickness of the air–blood barrier was much thinner; 0.56 ± 0.16 µm. TUNEL assay after birth revealed that the apoptotic cells were abundant and distributed in the epithelium lining of the pulmonary alveoli and the interstitium of the thick interalveolar septa. On the 7th day, and onward, the incidence of apoptotic cells decreased markedly. This study concluded that the lung development included two phases: the first phase (from birth to the 14th days) corresponds to the period of bulk alveolarization and microvascular maturation. The second phase (from the 14th days to the full maturity) corresponds to the lung growth and late alveolarization.

Kidney injury molecule-1 identifies antemortem injury in postmortem adult and fetal kidney

There is currently no technique to unambiguously diagnose antemortem kidney injury on postmortem examination since postmortem tissue damage and autolysis are common. We assessed the ability to detect kidney injury molecule-1 (KIM-1) expression in adult and fetal kidneys examined at autopsy. In adult kidneys ( n = 52 subjects), we found that the intensity of KIM-1 staining significantly correlated with the antemortem level of serum creatinine, and this was independent of the extent of tissue autolysis. In addition, kidneys from a total of 52 fetal/neonatal subjects, 30 stillborns and 22 liveborns, were assessed for KIM-1 staining. Given that serum creatinine is unreliable and often unavailable in fetuses and newborns, we assessed preterminal hypoxia in fetuses by the presence of squames in pulmonary alveoli and by required intubation. KIM-1 expression correlated with these clinical indexes of hypoxia. The expression of KIM-1 was seen in a majority of the fetal and neonatal autopsy kidneys (77%, 40/52) as early as 16 wk of gestation, even in the presence of autolysis. Thus KIM-1 is a specific and stable marker of antemortem tubular injury in kidneys of adults and fetuses despite postmortem autolysis.