Circum-menopausal changes in women's preferences for sexually dimorphic shape cues in peer-aged faces

Recent studies suggest that post-menopausal women demonstrate stronger preferences for feminine characteristics in male and female faces than do pre-menopausal women, potentially reflecting stronger preferences for healthy men and greater derogation of attractive women among more fertile women. A limitation of this work was that it assessed circum-menopausal women's face preferences using images of young adults only. Here, we found that post-menopausal women demonstrated stronger preferences for feminine characteristics in male and female peer-aged faces that did pre-menopausal women. These data present novel evidence for circum-menopausal variation in face perception and confirm that the circum-menopausal variation in face preferences observed previously was not an artefact of the young faces employed as stimuli.     

Renal involvement in primary Sjogren syndrome of childhood: case report and literature review

Renal tubular acidosis (RTA) is common in adults with primary Sjogren syndrome (pSS) but to date this condition has only been identified in 12 pediatric cases of pSS. Here we present the case of a 13-year-old, otherwise asymptomatic girl in whom the search for the etiology of incidentally found nephrocalcinosis led to diagnosis of distal RTA and nephrogenic diabetes insipidus secondary to SS-associated tubulointerstitial nephritis. Immunosupressive treatment and alkali/electrolyte supplementation resulted in stable renal function over the 6-year follow-up. A review of the literature focuses on two aspects of pSS: (1) the difficulties in diagnosing pSS in childhood and (2) clinical–pathological features, treatment and outcome of renal tubulointerstitial disease in childhood pSS. SS should be considered in older children, particularly females with otherwise unexplained RTA. A careful search for other renal dysfunctions is necessary, and renal biopsy may be of value in assessing the extent of renal damage and the need for immunomodulatory therapy.     

Lipophilic siderophores of Mycobacterium tuberculosis prevent cardiac reperfusion injury

Reperfusion injury, which occurs upon the reintroduction of blood flow to an ischemic organ, is responsible for considerable damage in heart attacks and strokes. However, no treatment for reperfusion injury is currently available. A major cause of reperfusion injury is the iron-mediated generation of hydroxyl radical (OH). In this study we have explored the capacity of novel iron chelators called “exochelins” to prevent reperfusion injury. Exochelins, siderophores of Mycobacterium tuberculosis, are unique iron chelators because they are lipid soluble, and hence able to enter cells rapidly. In the iron-free state, exochelins prevented OH formation. Desferri-exochelins prevented oxidative injury to cultured cardiac myocytes, and did so more rapidly and effectively than the nonlipid soluble iron chelator deferoxamine. The capacity of various desferri-exochelins to protect myocytes from oxidative injury varied directly with their solubility in lipid. Infused into isolated rabbit hearts during reperfusion after a period of ischemia, desferri-exochelins dramatically improved systolic and diastolic left ventricular function, preserved coronary flow, reduced release of the cardiac enzyme lactic dehydrogenase, and reduced myocardial concentrations of OH metabolites. Thus, highly diffusible desferri-exochelins block injury caused by OH production and have potential for the treatment of reperfusion injury.     

Modifications of Chest CT Body Composition Parameters at Three and Six Months after Severe COVID-19 Pneumonia: A Retrospective Cohort Study

We aimed to describe body composition changes up to 6–7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2–3 months (T1), and 6–7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) −1.11 (−1.72; −0.51) cm²] and in body fat areas were observed [−3.13 (−10.79; +4.52) cm² for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [−3.55 (−4.94; −2.17) cm²] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6–7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.     

Silencing of RhoA nucleotide exchange factor, ARHGEF3, reveals its unexpected role in iron uptake

Genomewide association meta-analysis studies have identified > 100 independent genetic loci associated with blood cell indices, including volume and count of platelets and erythrocytes. Although several of these loci encode known regulators of hematopoiesis, the mechanism by which most sequence variants exert their effect on blood cell formation remains elusive. An example is the Rho guanine nucleotide exchange factor, ARHGEF3, which was previously implicated by genomewide association meta-analysis studies in bone cell biology. Here, we report on the unexpected role of ARHGEF3 in regulation of iron uptake and erythroid cell maturation. Although early erythroid differentiation progressed normally, silencing of arhgef3 in Danio rerio resulted in microcytic and hypochromic anemia. This was rescued by intracellular supplementation of iron, showing that arhgef3-depleted erythroid cells are fully capable of hemoglobinization. Disruption of the arhgef3 target, RhoA, also produced severe anemia, which was, again, corrected by iron injection. Moreover, silencing of ARHGEF3 in erythromyeloblastoid cells K562 showed that the uptake of transferrin was severely impaired. Taken together, this is the first study to provide evidence for ARHGEF3 being a regulator of transferrin uptake in erythroid cells, through activation of RHOA.     

Detection of Leishmania donovani and L. tropica in Ethiopian wild rodents

Human visceral (VL, also known as Kala-azar) and cutaneous (CL) leishmaniasis are important infectious diseases affecting countries in East Africa that remain endemic in several regions of Ethiopia. The transmission and epidemiology of the disease is complicated due to the complex life cycle of the parasites and the involvement of various Leishmania spp., sand fly vectors, and reservoir animals besides human hosts. Particularly in East Africa, the role of animals as reservoirs for human VL remains unclear. Isolation of Leishmania donovani parasites from naturally infected rodents has been reported in several endemic countries; however, the status of rodents as reservoirs in Ethiopia remains unclear. Here, we demonstrated natural Leishmania infections in rodents. Animals were trapped in 41 localities of endemic and non-endemic areas in eight geographical regions of Ethiopia and DNA was isolated from spleens of 586 rodents belonging to 21 genera and 38 species. Leishmania infection was evaluated by real-time PCR of kinetoplast (k)DNA and confirmed by sequencing of the PCR products. Subsequently, parasite species identification was confirmed by PCR and DNA sequencing of the 18S ribosomal RNA internal transcribed spacer one (ITS1) gene. Out of fifty (8.2%) rodent specimens positive for Leishmania kDNA-PCR and sequencing, 10 were subsequently identified by sequencing of the ITS1 showing that five belonged to the L. donovani complex and five to L. tropica. Forty nine kDNA-positive rodents were found in the endemic localities of southern and eastern Ethiopia while only one was identified from northwestern Ethiopia. Moreover, all the ten ITS1-positive rodents were captured in areas where human leishmaniasis cases have been reported and potential sand fly vectors occur. Our findings suggest the eco-epidemiological importance of rodents in these foci of leishmaniasis and indicate that rodents are likely to play a role in the transmission of leishmaniasis in Ethiopia, possibly as reservoir hosts.     

Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP<Superscript>®</Superscript> Peptides) Conjugated with Different Fluorescent Dyes

Purpose

Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP^® peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors.

Procedures

Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP^® variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP^® variants in multidimensional space of spectral parameters.

Results

The fluorescently labeled pHLIP^® variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP^® peptide.

Conclusions

Different cargo molecules conjugated with pHLIP^® peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP^®-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.

     

Recovery of motor function after stroke: a polymyography-based analysis

We present a method for assessing muscle activation patterns during goal-directed movement. We present a cohort study from a randomized clinical trial that followed the recovery of motor function during and after intensive gait training, assisted by sensor-driven, four-channel electrical stimulation. The instrument that we developed allows for the simultaneous recordings of up to 16 channels that are wirelessly sent to a host computer, which then provides feedback to the subject. The inputs to the portable instrument support electromyography (EMG) amplifiers, inertial sensors and goniometers. We show that this method is sensitive enough to show changes in muscle activation patterns in stroke patients before and after gait training (four weeks, five days a week, 30 min daily). We also show that the recovery decreases the differences between patterns of muscle activities (e.g., levels of muscle activations and median frequencies) assessed in hemiplegic and healthy subjects. This method allows for the analysis of muscle contributions and activation patterns; therefore, it might be possible to better understand the physiology behind the recovery of function. This EMG analysis provides a quantification of recovery that is a valuable addition to other measures, such as the Fugl-Meyer score, the Berg-Balance score, gait speed, and the symmetry index.