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A 44-year-old male presents with shortness of breath, non-productive cough, and chest tightness to the ski clinic in Winter Park, Colorado. He flew from his home town, San Antonio, Texas, three days earlier. Symptoms began the day after arrival and progressively worsened over the course of the last 2 days. Shortness of breath is exacerbated by physical activity and relieved by rest. He tried his son’s albuterol inhaler with no improvement in his symptoms. He denied fevers, chills, and sick contacts. He is in excellent shape and has never experienced these symptoms before despite many similar ski trips. His past medical, family, and social histories are unremarkable, and he takes no medications. On arrival he appears generally healthy, but exhibits significantly labored breathing. He is afebrile and normotensive, but tachycardic (104 BPM) and hypoxic with an oxygen saturation of 61% on room air. His lung examination is significant for diffuse rales. Chest radiography was performed (Figure 1). Open in a separate window Figure 1. Chest Radiography 2. Arguments Against Based on the patient's history, physical examination, and radiographs, which one of the following is the most likely diagnosis? Atypical pneumonia Pulmonary embolism High altitude pulmonary edema Exercise induced bronchospasm Pneumothorax 3. Conclusions The answer is C: High altitude pulmonary edema (HAPE) is the leading cause of altitude-related death (1). It is characterized by non-cardiogenic pulmonary edema occurring with rapid ascent to altitudes above 2,500 m (1-3). This patient travelled from San Antonio, TX with altitude of 235 m to Winter Park, CO with altitude of 2,800 m. Risk factors for development of HAPE include prior history of altitude illness, higher altitude, rapid ascent, male sex, cold ambient temperatures, pre-existing respiratory infections, and intense exercise (1-3). Estimates of HAPE incidence vary, but have been reported as high as 4% in un-acclimatized mountaineers above 4,600 m (2). Onset of HAPE typically occurs within 1-4 days of ascent to altitude (3). Symptoms include fatigue, dyspnea on exertion, decreased exercise tolerance, low-grade fever, and dry cough which sometimes progresses to become productive of pink, frothy, sputum (2, 3). On physical examination, patients with HAPE are tachycardic, tachypneic, and hypoxic, frequently with low-grade fevers (1-3). Pulmonary examination reveals inspiratory crackles, initially in the right middle lobe, and becoming more diffuse and bilateral later in the illness (1-3). Chest x-ray (CXR) classically shows patchy perihilar opacities, sometimes with interstitial edema and pleural effusions. Heart size is normal, which is consistent with no cardiogenic pulmonary edema (3). The cornerstones of HAPE treatment are immediate descent to lower altitude and supplemental oxygen (1-3). If descent is not possible or supplemental oxygen not available, pharmacotherapy with nifedipine may be considered as the next line of treatment, with the goal being to decrease pulmonary artery pressure (1, 3) Several studies have suggested benefit with long acting beta agonists (e.g. salmeterol) and with phosphodiesterase-5 inhibitors, but no strong evidence for either exists (1, 3). Similarly, HAPE is best prevented by gradual ascent to altitude (1-3). Pharmacologic prophylaxis can be considered, particularly in those with a history of HAPE, with nifedipine as the first-line agent and other potential options including phosphodiesterase-5 inhibitors, long acting beta agonists, and dexamethasone (1-3). Atypical organisms account for up to 40% of community-acquired pneumonia (4). Patients usually present with fevers and productive cough (4). Lung examination may reveal rales and wheezing (4). Hypoxia is rare (4). CXR may reveal patchy or circumscribed opacities (4). Pulmonary embolism (PE) may present with a sudden episode of SOB at rest (5). CXR is non-diagnostic in patients with PE and most commonly shows atelectasis, non-specific parenchymal abnormalities, or pleural effusions (5). Less commonly, the classic signs of a peripheral wedge-shaped opacity may be seen (5). Exercise-induced bronchospasm causes dyspnea and chest tightness during or after exercise (6). Physical examination is usually unremarkable with occasional wheezing (6). CXR is usually normal or may show increased bronchial wall thickening or flattening of the diaphragm (6). Pneumothorax is a relatively common condition among adults and can present with dyspnea and pleuritic chest pain (5). Physical examination typically reveals decreased chest excursion as well as decreased breath sounds on the affected side (5). CXR usually demonstrates a visceral pleural line, beyond which no pulmonary markings are present and possible mediastinal shift (5, 7). Table 1. Summary table Condition Characteristics Atypical pneumonia Fever, productive cough; unilateral or bilateral heterogeneous, patchy, reticular, segmental, peribronchial opacifications on CXR a Pulmonary embolism Acute onset of cough, dyspnea, tachycardia, tachypnea, pleuretic chest pain, and hypoxia; CXR is usually normal, but a wedge-shaped opacity of the lung tissue may be present High altitude pulmonary edema Caused by rapid ascent to high altitude above 2,500m; cough, dyspnea, hypoxia; dense bilateral patchy opacities in variable locations Exercise induced bronchospasm Cough, dyspnea, and wheezing triggered by exercise; CXR is usually normal Pneumothorax Acute onset of dyspnea, pleuretic chest pain, diminished breath sounds; CXR may reveal displacement of visceral pleura and absence of pulmonary markings Open in a separate window a chest x-ray.

AbstractIn the spreading of infectious diseases, an important number to determine is how many other people will be infected on average by anyone who has become infected themselves. This is known as the reproduction number. This paper describes a non-parametric inverse method for extracting the full transfer function of infection, of which the reproduction number is the integral. The method is demonstrated by applying it to the timeline of hospitalisation admissions for covid-19 in the Netherlands up to May 20 2020, which is publicly available from the site of the Dutch National Institute of Public Health and the Environment (rivm.nl).

Lungfishes are the closest living relatives of the tetrapods, and the ear of recent lungfishes resembles the tetrapod ear more than the ear of ray-finned fishes and is therefore of interest for understanding the evolution of hearing in the early tetrapods. The water-to-land transition resulted in major changes in the tetrapod ear associated with the detection of air-borne sound pressure, as evidenced by the late and independent origins of tympanic ears in all of the major tetrapod groups. To investigate lungfish pressure and vibration detection, we measured the sensitivity and frequency responses of five West African lungfish ( Protopterus annectens ) using brainstem potentials evoked by calibrated sound and vibration stimuli in air and water. We find that the lungfish ear has good low-frequency vibration sensitivity, like recent amphibians, but poor sensitivity to air-borne sound. The skull shows measurable vibrations above 100 Hz when stimulated by air-borne sound, but the ear is apparently insensitive at these frequencies, suggesting that the lungfish ear is neither adapted nor pre-adapted for aerial hearing. Thus, if the lungfish ear is a model of the ear of early tetrapods, their auditory sensitivity was limited to very low frequencies on land, mostly mediated by substrate-borne vibrations.

Although pre-exposure prophylaxis (PrEP) is a key tool in HIV prevention efforts, little is known about PrEP as a prevention strategy for criminal justice-involved (CJI) women. The purpose of this study was to examine multilevel factors shaping PrEP awareness and acceptability among CJI women. Between January 2017 and December 2017, we conducted 52 interviews with CJI women at high risk for HIV and stakeholders from the criminal justice (CJ) and public health (PH) systems. Interviews explored awareness of PrEP and the multilevel factors shaping PrEP acceptability. Data were analyzed using inductive thematic analysis and executive summaries. Atlas.ti facilitated analyses. The majority of CJI women (n = 27) were, on average, 41.3 years, from racial and ethnic minority groups (56% Black/African-American; 19% Latinx) and reported engaging in recent high-risk behavior (nearly 60% engaged in transactional sex, 22% reported ≥ 4 sexual partners, and 37% reported injection drug use). Of system stakeholders (n = 25), 52% represented the CJ sector. Although CJI women were generally unaware of PrEP, attitudes toward PrEP were enthusiastic. Barriers to PrEP acceptability included medication side effects (individual level); distrust in HIV prevention mechanisms (community level); lack of local HIV prevention efforts among high-risk women (public policy/HIV epidemic stage level). Factors promoting PrEP included perceived HIV risk (individual level); PrEP being an HIV prevention method that women can control without partner negotiation (social and sexual network level); and availability of public health insurance (community level). Despite low awareness of PrEP, CJI women expressed positive attitudes toward PrEP. To improve PrEP access for CJI women, implementation efforts should address barriers and leverage facilitators across multiple levels to be maximally effective.

AbstractCellulose synthase-like D (CSLD) family was characterized for their expression and functions in Populus trichocarpa. Ten members, PtrCslD1-10, were identified in the P. trichocarpa genome, and they belong to 4 clades by phylogenetic tree analysis. qRT-PCR and promoter:GUS assays in Arabidopsis and P. trichocarpa displayed divergent expression patterns of these 10 PtrCSLD genes in root hairs, root tips, leaves, vascular tissues, xylem and flowers. Among PtrCslD2, PtrCslD4, PtrCslD5, PtrCslD6, and PtrCslD8 that all exhibited expression in root hairs, only PtrCslD5 could restore the root hairless phenotype of the atcsld3 mutant, demonstrating that PtrCslD5 is the functional ortholog of AtCslD3 for root hair formation. Our results suggest more possible functions for other PtrCslD genes in poplar.

Introduction Iron deficiency anemia (IDA) is an internationally recognized leading cause of disability and contributes to childhood morbidity and mortality. The prevalence of IDA is higher in developing countries, especially in Arab countries, compared to the west. Methods To assess the prevalence of IDA, we analyzed the data of children aged between one to five years seen at Dr. Sulaiman Al-Habib Medical Group's tertiary care hospital in Dubai, United Arab Emirates (UAE) from 2016 to 2018. Results We found a high occurrence of IDA in male children and non-Emirati children. Conclusion Appropriate screening and iron supplementation are required to see a decline in the rate of IDA. Further nationwide studies are required to identify the highly prevalent and high-risk areas of IDA in the UAE.

Recent studies suggest that Sirt inhibition may have beneficial effects on several human diseases such as neurodegenerative diseases and cancer. Coffee is one of most popular beverages with several positive health effects. Therefore, in this paper, potential Sirt inhibitors were screened using coffee extract. First, HPLC was utilized to fractionate coffee extract, then screened using a Sirt1/2 inhibition assay. The screening led to the isolation of a potent Sirt1/2 inhibitor, whose structure was determined as javamide-II (N-caffeoyltryptophan) by NMR. For confirmation, the amide was chemically synthesized and its capacity of inhibiting Sirt1/2 was also compared with the isolated amide. Javamide-II inhibited Sirt2 (IC50; 8.7 μM) better than Sirt1(IC50; 34μM). Since javamide-II is a stronger inhibitor for Sirt2 than Sirt1. The kinetic study was performed against Sirt2. The amide exhibited noncompetitive Sirt2 inhibition against the NAD+ (Ki = 9.8 μM) and showed competitive inhibition against the peptide substrate (Ki = 5.3 μM). Also, a docking simulation showed stronger binding pose of javamide-II to Sirt2 than AGK2. In cellular levels, javamide-II was able to increase the acetylation of total lysine, cortactin and histone H3 in neuronal NG108-15 cells. In the same cells, the amide also increased the acetylation of lysine (K382) in p53, but not (K305). This study suggests that Javamide-II found in coffee may be a potent Sirt1/2 inhibitor, probably with potential use in some conditions of human diseases.

AIM: To define sensitive and reliable Doppler parameters for measurements in the superior mesenteric artery and mural arteries of affected bowel loops used in the assessment of Crohn disease activity. ----- METHODS: We performed cross-sectional study at a tertiary care setting in Zagreb, Croatia, between January 2001 and March 2005. We measured arterial flow in the superior mesenteric artery and affected bowel wall in 138 patients with Crohn disease (74 with active, 64 with inactive disease) and 67 healthy volunteers. The disease activity was determined by the clinical examination, Crohn disease activity index, and standard laboratory tests. Superior mesenteric artery color and pulsed Doppler parameters were peak systolic velocity, end-diastolic velocity, resistance index, mean velocity flow, cross-sectional area, and flow volume. When gut mural vessels were identified, we performed spectral analysis of mural arteries by pulsed Doppler, with a measurement of resistance index. ----- RESULTS: The measurements in the superior mesenteric artery showed statistically and clinically significant difference in flow volume in active group, compared with inactive and control groups (C+/-Q=564+/-263 mL/min for active, 421+/-157 for inactive and 416+/-248 for control group). Affected bowel loops analysis showed significant difference between inactive and active Crohn disease group in wall thickness (3.1+/-1.4 vs 5.0+/-1.8 mm, P<0.001, Mann-Whitney test) while all participants from control group had thickness below 2mm. Intensity of color Doppler signals was different for all groups (P<0.001, chi(2) test) with the highest level of hyperemia in the active group. Resistance index measurements of mural arteries in bowel wall revealed differences between all three groups (0.61+/-0.05 in active group, 0.71+/-0.05 in the inactive group and 0.80+/-0.11 in the control group, P<0.001, Kruskal-Wallis test). ----- CONCLUSION: Intensity of color Doppler signals and resistance index measurements of mural arteries in the thickened bowel wall can be used as quantitative diagnostic tool in the assessment of Crohn disease activity.