Role of inflammatory mediators in resistance and susceptibility to pneumococcal infection

Variations in the host response during pneumonia caused by Streptococcus pneumoniae in susceptible (CBA/Ca) and resistant (BALB/c) inbred mouse strains were investigated. Significant differences were detected in survival time, core body temperature, lung-associated and systemic bacterial loads, mast cell numbers, magnitude and location of cytokine production, lung disruption, and ability of isolated lung cells to release the cytokine tumor necrosis factor (TNF) alpha in vitro. Overall, the results indicate that the reduced capacity of CBA/Ca mice to induce rapid TNF activity within the airways following infection with S. pneumoniae may be a factor in their elevated susceptibility to pneumococcal pneumonia.     

In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy

One of the major limitations in the current set of techniques available to neuroscientists is a dearth of methods for imaging individual cells deep within the brains of live animals. To overcome this limitation, we developed two forms of minimally invasive fluorescence microendoscopy and tested their abilities to image cells in vivo. Both one- and two-photon fluorescence microendoscopy are based on compound gradient refractive index (GRIN) lenses that are 350-1,000 microm in diameter and provide micron-scale resolution. One-photon microendoscopy allows full-frame images to be viewed by eye or with a camera, and is well suited to fast frame-rate imaging. Two-photon microendoscopy is a laser-scanning modality that provides optical sectioning deep within tissue. Using in vivo microendoscopy we acquired video-rate movies of thalamic and CA1 hippocampal red blood cell dynamics and still-frame images of CA1 neurons and dendrites in anesthetized rats and mice. Microendoscopy will help meet the growing demand for in vivo cellular imaging created by the rapid emergence of new synthetic and genetically encoded fluorophores that can be used to label specific brain areas or cell classes.     

Linear regression of eye velocity on eye position and head velocity suggests a common oculomotor neural integrator

The oculomotor system produces eye-position signals during fixations and head movements by integrating velocity-coded saccadic and vestibular inputs. A previous analysis of nucleus prepositus hypoglossi (nph) lesions in monkeys found that the integration time constant for maintaining fixations decreased, while that for the vestibulo-ocular reflex (VOR) did not. On this basis, it was concluded that saccadic inputs are integrated by the nph, but that the vestibular inputs are integrated elsewhere. We re-analyze the data from which this conclusion was drawn by performing a linear regression of eye velocity on eye position and head velocity to derive the time constant and velocity bias of an imperfect oculomotor neural integrator. The velocity-position regression procedure reveals that the integration time constants for both VOR and saccades decrease in tandem with consecutive nph lesions, consistent with the hypothesis of a single common integrator. The previous evaluation of the integrator time constant relied upon fitting methods that are prone to error in the presence of velocity bias and saccades. The algorithm used to evaluate imperfect fixations in the dark did not account for the nonzero null position of the eyes associated with velocity bias. The phase-shift analysis used in evaluating the response to sinusoidal vestibular input neglects the effect of saccadic resets of eye position on intersaccadic eye velocity, resulting in gross underestimates of the imperfections in integration during VOR. The linear regression method presented here is valid for both fixation and low head velocity VOR data and is easy to implement.     

Biochemical profile of blood serum of siraz <Emphasis Type="Italic">Capoeta capoeta umbla</Emphasis>

Seasonal changes in blood plasma biochemistry of siraz Capoeta capoeta umbla were determined throughout 1 year. In the present study, while the highest values for glucose and globulin were found in winter, the values for increased activities of total protein, albumin, calcium, sodium levels, albumin/globulin ratio, lactate dehydrogenase, and alkaline phosphatase were determined in summer. We determined that blood biochemistry values of siraz, which were positively affected by water temperature and pH, except glucose and globulin. Glucose and globulin were negatively affected by water temperature and pH. Consequently, it was concluded that the seasons are key factors when blood parameters are used as biomarkers for environmental alterations. It is difficult to define the most important factors affecting seasonal changes of blood biochemistry in fish.     

Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1.

We report the identification of mutations in lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) genes in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17. Linkage disequilibrium analysis of six families affected by NCIE permitted us to reduce a recently reported interval of 8.4 cM on chromosome 17p13.1 to a 600 kb region around the marker D17S1796, which contains LOX genes. LOX products have long been implicated in skin disorders. Two point mutations and one deletion were found in ALOXE3 and three point mutations were found in ALOX12B in these consanguineous families from the Mediterranean basin. ALOXE3 and ALOX12B are two genes which are physically linked and functionally related. They are separated by 38 kb, have one more exon than the other LOX genes and are mainly expressed in epithelial cells including keratinocytes. Although the main substrate(s) of the two enzymes is (are) still unknown, the products of ALOX12B obtained in experimental systems have been demonstrated to be of R-chirality. It seems likely that the product of one of these enzymes may be the substrate of the other, and that they belong to the same metabolic pathway.     

Spermatozoal nuclear determinants of reproductive outcome: implications for ART

A male factor is implicated in more than 50% of couples treated with IVF. However, neither the routine testing of male fertility potential nor its treatment address the specific mechanisms by which spermatozoal factors may impact upon reproductive outcome. An important function of spermatozoa is to deliver the paternal genome to the oocyte. Recently, a number of acquired spermatozoal nuclear factors that may have implications on reproductive outcome have been described. These include non-specific DNA strand breaks, numerical abnormalities in spermatozoal chromosome content, Y chromosome microdeletions and alterations in the epigenetic regulation of paternal genome. The exact mechanisms by which these factors affect reproduction are unknown and their implications for assisted reproduction technology outcome need to be further investigated. These recent findings point to the need for novel and more personalized approaches to test and treat male factor infertility.     

Neonates as intrinsically worthy recipients of pain management in neonatal intensive care

One barrier to optimal pain management in the neonatal intensive care unit (NICU) is how the healthcare community perceives, and therefore manages, neonatal pain. In this paper, we emphasise that healthcare professionals not only have a professional obligation to care for neonates in the NICU, but that these patients are intrinsically worthy of care. We discuss the conditions that make neonates worthy recipients of pain management by highlighting how neonates are (1) vulnerable to pain and harm, and (2) completely dependent on others for pain management. We argue for a relational account of ethical decision-making in the NICU by demonstrating how an increase in vulnerability and dependence may be experienced by the healthcare community and the neonate’s family. Finally, an ethical framework for decisions around neonatal pain management is proposed, focussing on surrogate decision-making and the importance of compassionate action through both a reflective and an affective empathy. As empathy can be highly motivating against pain, we propose that, in addition to educational programs that raise awareness and knowledge of neonatal pain and pain management, healthcare professionals must cultivate empathy in a collective manner, where all members of the NICU team, including parents, are compassionate decision-makers.

     

The effect of cardiovascular morbidity on clinical response provided by tadalafil in patients with erectile dysfunction

We aimed to investigate the association between erectile dysfunction and severity of cardiovascular morbidity and to assess clinical responses to tadalafil of patients in different cardiovascular risk groups. Between November 2019 and August 2020, a total of 258 male patients aged 45–70 years with ED were included. They were divided into three groups according to the Framingham risk score: low-risk (n: 86, 33.3%), intermediate-risk (n: 103, 39.9%) and high-risk (n: 69, 26.8%). At admission, all domains of the International Index of Erectile Function score were worse in high-risk group compared to other risk groups (p < .001). After a 12-week follow-up, a more significant improvement was observed in all domains of erectile function in all risk groups, but high-risk group had lower sexual scores (p < .001). The lowest rate for complete responsiveness to tadalafil was observed in the high-risk group (37.7%). The rate of failure in complete responsiveness was found to be 4.127 times greater with higher Framingham score and 3.102 times greater with higher erectile dysfunction severity at admission. Our preliminary findings show that more severe sexual disorders are observed in high-risk patients with cardiovascular morbidity. Individualised treatment may be important in high-risk group since they may benefit less from tadalafil, and failure in complete responsiveness can be more common in this group.