Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.     

The role of stimulus type in age-related changes of visual working memory

Aging is accompanied by increasing difficulty in working memory associated with the temporary storage and processing of goal-relevant information. Face recognition plays a preponderant role in human behavior, and one might therefore suggest that working memory for faces is spared from age-related decline compared to socially less important visual stimulus material. To test this hypothesis, we performed working memory (n-back) tasks with two different visual stimulus types, namely faces and doors, and compared them to tasks with primarily verbal material, namely letters. Age-related reaction time slowing was comparable for all three stimulus types, supporting hypotheses on general cognitive and motor slowing. In contrast, performance substantially declined with age for faces and doors, but little for letters. Working memory for faces resulted in significantly better performance than that for doors and was more sensitive to on-line manipulation errors such as the temporal order. All together, our results show that even though face perception might play a specific role in visual processing, visual working memory for faces undergoes the same age-related decline as it does for socially less relevant visual material. Moreover, these results suggest that working memory decline cannot be solely explained by increasing vulnerability in prefrontal cortex related to executive functioning, but indicate an age-related decrease in a visual short-term buffer, possibly located in the temporal cortex.     

A comparative study of 14 cases of familial and nonfamilial pheochromocytomas

A comparison is made between epidemiological features found in a group of 14 patients with familial and nonfamilial pheochromocytomas at M. D. Anderson Hospital and Tumor Institute. The Sipple syndrome (familial) group comprised eitht patients from three different families, and the nonfamilial group consisted of six nonrelated patients. The main differences were noted in the age of onset, sex ratio, bilaterality, malignant behavior, and occurrence of a second nonendocrine primary tumor. An attempt was made by light microscopy to define features that would indicate malignant behavior. No such features could be delineated. Survival time was unrelated to the presence of pheochromocytoma except in operative and investigative procedures.     

Characterization of water-soluble shrimp allergens released during boiling

Water-soluble shrimp allergens released during boiling (shrimp water) were characterized and compared to allergen extracts from boiled shrimp (shrimp meat). Both shrimp extracts contained acidic proteins (isoelectrofocusing) and demonstrated similar allergenic activity (RAST and RAST inhibition). Shrimp-water extract was analyzed further by immunoprinting with sera from 14 shrimp-sensitive, RAST-positive subjects, and six nonsensitive, RAST-negative individuals. Although none of the sera from shrimp-tolerant individuals reacted, 12/14 sera (85.7%) from shrimp-sensitive subjects reacted with shrimp-water proteins with acid isoelectric points. Shrimp-water extract was fractionated by chromatofocusing with pH and NaCl gradients. A number of eluted ultraviolet-absorbing peaks contained allergens as determined by RAST inhibition. Isoelectrofocusing demonstrated many protein bands present in these peaks, some of which bound IgE from a RAST-positive sera pool. These studies indicate that shrimp water is an excellent source of shrimp allergens, that chromatofocusing is a useful method for fractionation of shrimp allergens, and that shrimp allergens are generally protein molecules with acid isoelectric points.     

Primary Immunodeficiency Syndrome in Spain: First Report of the National Registry in Children and Adults

The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID) were registered in patients diagnosed between January 1980 and December 1995. PID diagnosis was made according to the World Health Organization criteria. The most frequent disorders were IgA deficiency (n = 394) and common variable immunodeficiency (n = 213), followed by severe combined immunodeficiency (n = 61), C1 inhibitor deficiency (n = 52), X-Iinked agammaglobulinemia (n = 49), IgG subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A comparative study between REDIP and data recently obtained from the European registry (ESID Report, 1995) revealed important differences between phagocytic disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and 6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell and combined deficiencies concurred with those reported in the European registry, 69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the geographical distribution of cases submitted may indicate underdiagnosis of PID in some country areas; surprisingly, the interval between the onset of clinical symptoms and diagnosis was significant, even in immunodeficiency diseases, such as IgA deficiency, which are easy to diagnose.     

Influence of the COVID-19 Pandemic on the Lifestyles of Health Sciences University Students in Spain: A Longitudinal Study

The COVID-19 pandemic has significantly impacted daily activities worldwide. University students may have experienced substantial changes in daily living as a result of restrictions on university attendance. The return to normalcy may take a long time, and understanding the influence that shifts in daily routines have had on the lifestyles of university students may inform approaches to support overall well-being. We analyzed changes in the lifestyles of students enrolled at a health sciences university during the COVID-19 pandemic. This longitudinal study took place at the Faculty of Medicine and Nursing in the University of the Basque Country in Spain, and the final sample consisted of 113 nursing students, 109 medical students, and 45 physiotherapy students. Our results demonstrate changes in lifestyles of university students during the pandemic. MedDiet adherence scores and the percentage of students with high adherence increased during the pandemic. This increase was due to the increased consumption of vegetables and nuts. In terms of physical activity, the practice of moderate and intense physical activity was maintained. These results provide important information for both public health authorities and educational institutions to guide strategies to maintain the well-being of students and enhance opportunities for young adults to lead a healthy lifestyle.     

Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice

The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasion. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Prevalence and mortality of patients with palliative needs in an acute respiratory setting

IntroductionNECPAL is a tool for identification of patients with advanced chronic disease in need of palliative care. The main objective of the study is to know the prevalence of patients with palliative needs in an acute respiratory ward in a Spanish tertiary hospital using NECPAL. A second objective of the study is to know the annual mortality rate of these patients.Materials and methodsCross sectional study and prospective monitoring of a cohort identified as palliative patients with the NECPAL tool for 12 months. Patient identification was performed in patients admitted to the respiratory ward of our hospital for longer than 3 days. We have assessed the annual vital status (deceased or not deceased) of patients and have recorded demographics, clinical and functional data, as well as the use of healthcare resources.ResultsWe monitored a cohort of 363 patients. Of them, 87 patients (24.3%) (IC 95% 19–30) were identified as NECPAL positive. 60% of patients (n = 64) died within 12 months of their admission. There was no significant difference in the mortality ratio of oncologic versus non oncologic patients. In a multivariable analysis, mortality was associated with demand by patients or relatives for palliative care and with the presence of specific disease progression markers or indicators.Conclusionsprevalence of patients with palliative needs in acute respiratory wards is high (one out of four patients). 60% of the patients identified as NECPAL positive in our cohort died in the first 12 months. Training of healthcare professionals as well as availability of appropriate resources are indispensable factors to improve care of this population.     

Country watch: Chile

In anticipation of social discrimination, an estimated 65% of parents of HIV-infected children in Chile do not inform school authorities of their child's infection. In several well-publicized cases, disclosure of a child's HIV status resulted in the child's expulsion from a preschool or primary school. In response to this situation, the Faculty of Education of Bias Canas Catholic University launched a program in 1992 aimed at educating teachers about HIV/AIDS and the special needs of infected children. The program is being implemented, in conjunction with the Interdisciplinary Project on Children and HIV/AIDS, in the cities with the highest HIV prevalences: Antafagasta, Concepcion, Valparaiso, and Santiago. Community-based educational programs have been organized to dispel misinformation about HIV/AIDS and counter prejudice. In addition, programs for teachers focused on the integration of HIV-infected children into the school system have been held. Costs for the teacher training are shared by the participating teachers, their school, and the program. A second program--Integral Attention for Seropositive Children--has been initiated and university students connected to the program are serving as interns in Santiago preschools. The experiences of both these programs have been recounted in a manual and video.