Effect of shape on liquid-vapor coexistence and surface properties of parallelepiped molecules.

Liquid-vapor coexistence is calculated via molecular dynamics for a variety of parallelepiped shaped molecules. Models are constructed as an array of tangential hard spheres interacting with an attractive square-well potential. Each shape is formed by varying the number of spheres in their three sides. The initial density of the system is chosen close to the critical density of a SW fluid to obtain an equilibrated liquid-vapor coexistence curve by the process of spinodal decomposition. A pattern that relates the geometry of the molecular models and the existence or non-existence of a liquid-vapor orthobaric curve is shown.

Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial.

INTRODUCTION: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma. METHODS: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure. CONCLUSIONS: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.

Impact of the tsunami caused by the Hunga Tonga-Hunga Ha'apai eruption in Costa Rica on 15 January 2022.

Hunga Tonga-Hunga Ha'apai had a large eruption (VEI 5-6) on 15 January 2022, which caused a tsunami recorded in all ocean basins. Costa Rica has made many advances in tsunami preparation over the past 9 years since the creation of SINAMOT (Sistema Nacional de Monitoreo de Tsunamis, National Tsunami Monitoring System), both on watch and warning protocols and on community preparedness. For the Hunga Tonga-Hunga Ha'apai event, the government declared a low-threat warning, suspending all in-water activities, even though the country did not receive any official warning from PTWC (Pacific Tsunami Warning Center) due to the lack of procedures for tsunamis generated by volcanoes. The tsunami was observed at 24 locations on both the Pacific and Caribbean coasts of Costa Rica, becoming the second most recorded tsunami in the country, after the 1991 Limon tsunami along the Caribbean coast. At 22 of those locations along the continental Pacific coast, observations were made by eyewitnesses, including one collocated with the sea level station at Quepos, which registered the tsunami. At Cocos Island (~ 500 km southwest of the continental Costa Rica, in the Pacific Ocean), several eyewitnesses reported the tsunami at two locations, and it was recorded at the sea level station. The tsunami was also recorded at the sea level station on the Caribbean coast. The tsunami effects reported were a combination of sea level fluctuations, strong currents, and coastal erosion, proving that the response actions were adequate for the size of the tsunami. Tsunami preparedness and the largest waves arriving during a dry season Saturday afternoon allowed the large number of eyewitness reports. This event then increased tsunami awareness in the country and tested protocols and procedures. Still, many people along the coast were not informed of the tsunami during the alert due to their remote location, the short notice of the warning, and a lack of procedures for some communities. There is thus still much work to do, particularly about warning dissemination, a direction in which communities should take an active role. Supplementary Information: The online version contains supplementary material available at 10.1007/s00445-023-01648-x.

A novel strategy to avoid sensitivity loss in pooled testing for SARS-CoV-2 surveillance: validation using nasopharyngeal swab and saliva samples.

At the peak of the COVID-19 pandemic, pooled surveillance strategies were employed to alleviate the overwhelming demand for clinical testing facilities. A major drawback of most pooled-testing methods is the dilution of positive samples, which leads to a loss of detection sensitivity and the potential for false negatives. We developed a novel pooling strategy that compensates for the initial dilution with an appropriate concentration during nucleic acid extraction and real-time PCR. We demonstrated the proof of principle using laboratory-created 10-sample pools with one positive and corresponding individual positive samples by spiking a known amount of heat-inactivated SARS-CoV-2 into viral transport medium (VTM) or pooled negative saliva. No Ct difference was observed between a 10-sample pool with one positive vs. the corresponding individually analyzed positive sample by this method, suggesting that there is no detectable loss of sensitivity. We further validated this approach by using nasopharyngeal swab (NPS) specimens and showed that there is no loss of sensitivity. Serial dilutions of the virus were spiked into VTM and pooled with negative saliva in simulated 10-sample pools containing one positive to determine the LOD and process efficiency of this pooling methodology. The LOD of this approach was 10 copies/PCR, and the process efficiencies are ~95%-103% for N1 and ~87%-98% for N2 with samples in different matrices and with two different master mixes tested. Relative to TaqPath 1-step master mix, the TaqMan Fast Virus 1-Step master mix showed better sensitivity for the N2 assay, while the N1 assay showed no Ct difference. Our pooled testing strategy can facilitate large-scale, cost-effective SARS-CoV-2 surveillance screening and maintain the same level of sensitivity when analyzed individually or in a pool. This approach is highly relevant for public health surveillance efforts aimed at mitigating SARS-CoV-2 spread.

[Pulmonary arterial hypertension and renal impairment in patients from the National Institute of Cardiology Dr. Ignacio Chávez, Mexico]. / Hipertensión arterial pulmonar y deterioro renal en pacientes del Instituto Nacional de Cardiología Ignacio Chávez, México.

Objective: The objective of the study was to describe the clinical characteristics and the evolution of the severity of pulmonary arterial hypertension (PAH) and the degree of renal failure. Material and methods: A retrospective observational study was carried out in which the physical and electronic medical records of 60 patients older than 18 years with a diagnosis of pulmonary arterial hypertension were analyzed. Results: In our study, 11.4% of the severe PAH group worsened renal function at six months, and 13.6% of the participants worsened it at one year. In contrast, in the group with moderate PAH, 18.8% worsened at six months, and 12.5% worsened at one year. Also, the GFR at one year was 54.15 mL/min/1.73 m2 in the moderate PAH group and in the severe PAH group was 73.55 mL/min/1.73 m2. Conclusion: The results of this research suggest that the deterioration of kidney function is related to the severity of pulmonary arterial hypertension.

Terapia de REGEN COV como base de terapia inmunomoduladora mixta en pacientes hospitalizados por neumonía por SARS-CoV-2: Serie de casos / REGEN COV Therapy as the Basis of Mixed Immunomodulatory Therapy in Patients Hospitalized for SARS- CoV-2 Pneumonia: Case Series

Los países en desarrollo con sistema de salud de baja inversión encuentran un reto en priorizar el tratamiento de COVID-19 según su eficacia y sus costos. Materiales y métodos: se explora la utilidad hospitalaria de una intervención segura con eficacia ambulatoria comprobada. Se describe la administración de un tratamiento inmunomodulador combinado a base de imdevimab y casirivimab (REGEN COV). Resultados: los resultados individualizados apuntan a resultados prometedores en pacientes de alto riesgo a progresión y mortalidad. Conclusión: se ha demostrado que REGEN COV es eficiente para tratar dicha enfermedad. Sin embargo, se necesitan ensayos clínicos aleatorizados para comprobar su eficacia en combinación. (AU)

Developing countries with low-investment health systems find it challenging to prioritize COVID-19 treatment according to its efficacy and affordability. Materials and methods: therefore, the in-hospital utility of a safe intervention with outpatient efficacy is explored. We describe the administration of immunomodulatory combination therapy based on imdevimab and casirivimab (REGEN COV). Results: individualized results point to promising outcomes in patients at high risk of progression and mortality. Conclusion: REGEN COV has been shown to be efficient in treating said disease. However, randomized clinical trials are needed to verify their efficacy in combination. (AU)

MALDI-TOF MS Affords Discrimination of Deinococcus aquaticus Isolates Obtained From Diverse Biofilm Habitats.

Matrix-assisted Laser Desorption Ionization-Time of Flight Mass Spectroscopy (MALDI-TOF MS) has been used routinely over the past decade in clinical microbiology laboratories to rapidly characterize diverse microorganisms of medical importance both at the genus and species levels. Currently, there is keen interest in applying MALDI-TOF MS at taxonomic levels beyond species and to characterize environmental isolates. We constructed a model system consisting of 19 isolates of Deinococcus aquaticus obtained from biofilm communities indigenous to diverse substrates (concrete, leaf tissue, metal, and wood) in the Fox River - Lake Winnebago system of Wisconsin to: (1) develop rapid sample preparation methods that produce high quality, reproducible MALDI-TOF spectra and (2) compare the performance of MALDI-TOF MS-based profiling to common DNA-based approaches including 16S rRNA sequencing and genomic diversity by BOX-A1R fingerprinting. Our results suggest that MALDI-TOF MS can be used to rapidly and reproducibly characterize environmental isolates of D. aquaticus at the subpopulation level. MALDI-TOF MS provided higher taxonomic resolution than either 16S rRNA gene sequence analysis or BOX-A1R fingerprinting. Spectra contained features that appeared to permit characterization of isolates into two co-occurring subpopulations. However, reliable strain-level performance required rigorous and systematic standardization of culture conditions and sample preparation. Our work suggests that MALDI-TOF MS offers promise as a rapid, reproducible, and high-resolution approach to characterize environmental isolates of members of the genus Deinococcus. Future work will focus upon application of methods described here to additional members of this ecologically diverse and ubiquitous genus.

Throwing induces substantial torsional adaptation within the midshaft humerus of male baseball players.

Athletes participating in unilateral dominant sports are useful models for investigating skeletal responses to mechanical loading as they provide controlled evidence in the absence of completing a randomized controlled trial. Throwing athletes may be an additional model for this purpose as they overload their dominant upper extremity enabling the contralateral side to act as an internal control and load the bones of the upper extremity purely via the generation of internal (i.e. muscular) forces without superposition of externally applied loads (i.e. impact with an external object). The aim of this study was to investigate upper extremity bone adaptation in throwing athletes and explore factors that predict this adaptation. Two cohorts were recruited-male baseball players (throwers; n=15) and matched controls (controls; n=15). Each subject was assessed for shoulder range and strength, and upper extremity bone mass, structure and estimated strength. Throwers had substantially greater skeletal differences between their dominant and nondominant upper extremities than controls, indicating that throwing induces greater adaptation than induced by habitual loading of the dominant upper extremity. Bone adaptation in throwers was localized to the humerus, with the midshaft humerus in the dominant upper extremity of throwers having enhanced bone mass, structure and estimated strength. The largest effect was for estimated strength of the midshaft humerus which had 30% greater polar moment of inertia (I(P)) in throwers and suggests adaptation to resist torsional loads. The skeletal effect of throwing at the midshaft humerus was influenced by playing position with pitchers and catchers displaying greater dominant-to-nondominant differences than fielders, and was predicted by years throwing and dominant-to-nondominant difference in upper arm lean cross-sectional area. The latter two variables explained 67% of the variance in dominant-to-nondominant differences in I(P). Collectively, these data indicate that throwing induces substantial adaptation within the midshaft humerus. Adaptation was primarily in the direction of torsion which is consistent with biomechanical and injury data suggesting throwing introduces high magnitude torsional forces. As the magnitude of adaptation in throwers was equivalent to that observed in athletes participating in other unilateral dominant sports, throwers represent an alternative model for investigating the skeletal effects of mechanical loading.