Does Plant Species Richness Guarantee the Resilience of Local Medical Systems? A Perspective from Utilitarian Redundancy

Resilience is related to the ability of a system to adjust to disturbances. The Utilitarian Redundancy Model has emerged as a tool for investigating the resilience of local medical systems. The model determines the use of species richness for the same therapeutic function as a facilitator of the maintenance of these systems. However, predictions generated from this model have not yet been tested, and a lack of variables exists for deeper analyses of resilience. This study aims to address gaps in the Utilitarian Redundancy Model and to investigate the resilience of two medical systems in the Brazilian semi-arid zone. As a local illness is not always perceived in the same way that biomedicine recognizes, the term “therapeutic targets” is used for perceived illnesses. Semi-structured interviews with local experts were conducted using the free-listing technique to collect data on known medicinal plants, usage preferences, use of redundant species, characteristics of therapeutic targets, and the perceived severity for each target. Additionally, participatory workshops were conducted to determine the frequency of targets. The medical systems showed high species richness but low levels of species redundancy. However, if redundancy was present, it was the primary factor responsible for the maintenance of system functions. Species richness was positively associated with therapeutic target frequencies and negatively related to target severity. Moreover, information about redundant species seems to be largely idiosyncratic; this finding raises questions about the importance of redundancy for resilience. We stress the Utilitarian Redundancy Model as an interesting tool to be used in studies of resilience, but we emphasize that it must consider the distribution of redundancy in terms of the treatment of important illnesses and the sharing of information. This study has identified aspects of the higher and lower vulnerabilities of medical systems, adding variables that should be considered along with richness and redundancy.     

Elevated Intracranial Pressure and Cerebral Edema following Permanent MCA Occlusion in an Ovine Model

Introduction

Malignant middle cerebral artery (MCA) stroke has a disproportionately high mortality due to the rapid development of refractory space-occupying cerebral edema. Animal models are essential in developing successful anti-edema therapies; however to date poor clinical translation has been associated with the predominately used rodent models. As such, large animal gyrencephalic models of stroke are urgently needed. The aim of the study was to characterize the intracranial pressure (ICP) response to MCA occlusion in our recently developed ovine stroke model.

Materials and Methods

30 adult female Merino sheep (n = 8–12/gp) were randomized to sham surgery, temporary or permanent proximal MCA occlusion. ICP and brain tissue oxygen were monitored for 24 hours under general anesthesia. MRI, infarct volume with triphenyltetrazolium chloride (TTC) staining and histology were performed.

Results

No increase in ICP, radiological evidence of ischemia within the MCA territory but without space-occupying edema, and TTC infarct volumes of 7.9+/-5.1% were seen with temporary MCAO. Permanent MCAO resulted in significantly elevated ICP, accompanied by 30% mortality, radiological evidence of space-occupying cerebral edema and TTC infarct volumes of 27.4+/-6.4%.

Conclusions

Permanent proximal MCAO in the sheep results in space-occupying cerebral edema, raised ICP and mortality similar to human malignant MCA stroke. This animal model may prove useful for pre-clinical testing of anti-edema therapies that have shown promise in rodent studies.     

Neisseria gonorrhoeae Modulates Immunity by Polarizing Human Macrophages to a M2 Profile

Current data suggest that Neisseria gonorrhoeae is able to suppress the protective immune response at different levels, such as B and T lymphocytes and antigen-presenting cells. The present report is focused on gonococcus evasion mechanism on macrophages (MФ) and its impact in the subsequent immune response. In response to various signals MФ may undergo classical-M1 (M1-MФ) or alternative-M2 (M2-MФ) activation. Until now there are no reports of the gonococcus effects on human MФ polarization. We assessed the phagocytic ability of monocyte-derived MФ (MDM) upon gonococcal infection by immunofluorescence and gentamicin protection experiments. Then, we evaluated cytokine profile and M1/M2 specific-surface markers on MФ challenged with N. gonorrhoeae and their proliferative effect on T cells. Our findings lead us to suggest N. gonorrhoeae stimulates a M2-MФ phenotype in which some of the M2b and none of the M1-MФ-associated markers are induced. Interestingly, N. gonorrhoeae exposure leads to upregulation of a Programmed Death Ligand 1 (PD-L1), widely known as an immunosuppressive molecule. Moreover, functional results showed that N. gonorrhoeae-treated MФ are unable to induce proliferation of human T-cells, suggesting a more likely regulatory phenotype. Taken together, our data show that N. gonorroheae interferes with MФ polarization. This study has important implications for understanding the mechanisms of clearance versus long-term persistence of N. gonorroheae infection and might be applicable for the development of new therapeutic strategies.     

Optimizing Culture Medium Composition to Improve Oligodendrocyte Progenitor Cell Yields In Vitro from Subventricular Zone-Derived Neural Progenitor Cell Neurospheres

Neural Stem and Progenitor Cells (NSC/NPC) are gathering tangible recognition for their uses in cell therapy and cell replacement therapies for human disease, as well as a model system to continue research on overall neural developmental processes in vitro. The Subventricular Zone is one of the largest NSC/NPC niches in the developing mammalian Central Nervous System, and persists through to adulthood. Oligodendrocyte progenitor cell (OPC) enriched cultures are usefull tools for in vitro studies as well as for cell replacement therapies for treating demyelination diseases. We used Subventricular Zone-derived NSC/NPC primary cultures from newborn mice and compared the effects of different growth factor combinations on cell proliferation and OPC yield. The Platelet Derived Growth Factor-AA and BB homodimers had a positive and significant impact on OPC generation. Furthermore, heparin addition to the culture media contributed to further increase overall culture yields. The OPC generated by this protocol were able to mature into Myelin Basic Protein-expressing cells and to interact with neurons in an in vitro co-culture system. As a whole, we describe an optimized in vitro method for increasing OPC.     

A Cross-Reactive Human Single-Chain Antibody for Detection of Major Fish Allergens,Parvalbumins, and Identification of a Major IgE-Binding Epitope

Fish allergy is associated with moderate to severe IgE-mediated reactions to the calcium binding parvalbumins present in fish muscle. Allergy to multiple fish species is caused by parvalbumin-specific cross-reactive IgE recognizing conserved epitopes. In this study, we aimed to produce cross-reactive single chain variable fragment (scFv) antibodies for the detection of parvalbumins in fish extracts and the identification of IgE epitopes. Parvalbumin-specific phage clones were isolated from the human ETH-2 phage display library by three rounds of biopanning either against cod parvalbumin or by sequential biopanning against cod (Gad m 1), carp (Cyp c 1) and rainbow trout (Onc m 1) parvalbumins. While biopanning against Gad m 1 resulted in the selection of clones specific exclusively for Gad m 1, the second approach resulted in the selection of clones cross-reacting with all three parvalbumins. Two clones, scFv-gco9 recognizing all three parvalbumins, and scFv-goo8 recognizing only Gad m 1 were expressed in the E. coli non-suppressor strain HB2151 and purified from the periplasm. scFv-gco9 showed highly selective binding to parvalbumins in processed fish products such as breaded cod sticks, fried carp and smoked trout in Western blots. In addition, the scFv-gco9-AP produced as alkaline phosphatase fusion protein, allowed a single-step detection of the parvalbumins. In competitive ELISA, scFv-gco9 was able to inhibit binding of IgE from fish allergic patients’ sera to all three β-parvalbumins by up to 80%, whereas inhibition by scFv-goo8 was up to 20%. ¹H/¹⁵N HSQC NMR analysis of the rGad m 1:scFv-gco9 complex showed participation of amino acid residues conserved among these three parvalbumins explaining their cross-reactivity on a molecular level. In this study, we have demonstrated an approach for the selection of cross-reactive parvalbumin-specific antibodies that can be used for allergen detection and for mapping of conserved epitopes.     

Surgical and Non-Surgical Procedures Associated with Recurrence of Periodontitis in Periodontal Maintenance Therapy: 5-Year Prospective Study

Background and Objective

Prospective studies that investigated the influence of surgical and nonsurgical procedures in the recurrence of periodontitis and tooth loss in periodontal maintenance therapy (PMT) programs have not been previously reported. The objective of this study was to evaluate longitudinally the recurrence of periodontitis in regular compliers (RC) and irregular compliers (IC) individuals undergoing surgical and non-surgical procedures over 5 years in a program of PMT.

Materials and Methods

A total of 212 individuals participated in this study. Full-mouth periodontal examination including bleeding on probing, probing depth, and clinical attachment level were determined at all PMT visits over 5 years. The recurrence of periodontitis was evaluated in RC and IC individuals undergoing surgical and non-surgical procedures in PMT. The influences of risk variables of interest were tested through univariate analysis and multivariate logistic regression.

Results

Recurrence of periodontitis was significantly lower among RC when compared to IC. Individuals with recurrence of periodontitis and undergoing surgical procedures showed higher probing depth and clinical attachment loss than those who received non-surgical procedures. Recurrence of periodontitis was higher in individual undergoing surgical procedures and irregular compliance during PMT.

Conclusions

Irregular compliance and surgical procedures in individuals undergoing PMT presented higher rates of recurrence of periodontitis when compared to regular compliant patients undergoing non-surgical procedures.     

Legacy of Pre-Disturbance Spatial Pattern Determines Early Structural Diversity following Severe Disturbance in Montane Spruce Forests

Background

Severe canopy-removing disturbances are native to many temperate forests and radically alter stand structure, but biotic legacies (surviving elements or patterns) can lend continuity to ecosystem function after such events. Poorly understood is the degree to which the structural complexity of an old-growth forest carries over to the next stand. We asked how pre-disturbance spatial pattern acts as a legacy to influence post-disturbance stand structure, and how this legacy influences the structural diversity within the early-seral stand.

Methods

Two stem-mapped one-hectare forest plots in the Czech Republic experienced a severe bark beetle outbreak, thus providing before-and-after data on spatial patterns in live and dead trees, crown projections, down logs, and herb cover.

Results

Post-disturbance stands were dominated by an advanced regeneration layer present before the disturbance. Both major species, Norway spruce (Picea abies) and rowan (Sorbus aucuparia), were strongly self-aggregated and also clustered to former canopy trees, pre-disturbance snags, stumps and logs, suggesting positive overstory to understory neighbourhood effects. Thus, although the disturbance dramatically reduced the stand’s height profile with ~100% mortality of the canopy layer, the spatial structure of post-disturbance stands still closely reflected the pre-disturbance structure. The former upper tree layer influenced advanced regeneration through microsite and light limitation. Under formerly dense canopies, regeneration density was high but relatively homogeneous in height; while in former small gaps with greater herb cover, regeneration density was lower but with greater heterogeneity in heights.

Conclusion

These findings suggest that pre-disturbance spatial patterns of forests can persist through severe canopy-removing disturbance, and determine the spatial structure of the succeeding stand. Such patterns constitute a subtle but key legacy effect, promoting structural complexity in early-seral forests as well as variable successional pathways and rates. This influence suggests a continuity in spatial ecosystem structure that may well persist through multiple forest generations.     

Inflammatory Bowel Disease and Risk of Adverse Pregnancy Outcomes

Background and Objectives

Existing data on pregnancy complications in inflammatory bowel disease (IBD) are inconsistent. To address these inconsistencies, we investigated potential associations between IBD, IBD-related medication use during pregnancy, and pregnancy loss, pre-eclampsia, preterm delivery, Apgar score, and congenital abnormalities.

Methods

We conducted a cohort study in >85,000 Danish National Birth Cohort women who were pregnant in the period 1996-2002 and had information on IBD, IBD-related medication use (systemic or local corticosteroids, 5-aminosalicylates), pregnancy outcomes and potential confounders. We evaluated associations between IBD and adverse pregnancy/birth outcomes using Cox regression and log-linear binomial regression.

Results

IBD was strongly and significantly associated with severe pre-eclampsia, preterm premature rupture of membranes and medically indicated preterm delivery in women using systemic corticosteroids during pregnancy (hazard ratios [HRs] >7). IBD was also associated with premature preterm rupture of membranes in women using local corticosteroid medications (HR 3.30, 95% confidence interval [CI] 1.33-8.20) and with medically indicated preterm delivery (HR 1.91, 95% CI 0.99-3.68) in non-medicated women. Furthermore, IBD was associated with low 5-minute Apgar score in term infants (risk ratio [RR] 2.19, 95% CI 1.03-4.66). Finally, Crohn’s disease (but not ulcerative colitis) was associated with major congenital abnormalities in the offspring (RR 1.85, 95% CI 1.06-3.21). No child with a congenital abnormality born to a woman with IBD was exposed to systemic corticosteroids in utero.

Conclusion

Women with IBD are at increased risk of severe pre-eclampsia, medically indicated preterm delivery, preterm premature rupture of membranes, and delivering infants with low Apgar score and major congenital malformations. These associations are only partly explained by severe disease as reflected by systemic corticosteroid use.     

The “Reading the Mind in the Eyes” Test: Complete Absence of Typical Sex Difference in ~400 Men and Women with Autism

The “Reading the Mind in the Eyes” test (Eyes test) is an advanced test of theory of mind. Typical sex difference has been reported (i.e., female advantage). Individuals with autism show more difficulty than do typically developing individuals, yet it remains unclear how this is modulated by sex, as females with autism have been under-represented. Here in a large, non-male-biased sample we test for the effects of sex, diagnosis, and their interaction. The Eyes test (revised version) was administered online to 395 adults with autism (178 males, 217 females) and 320 control adults (152 males, 168 females). Two-way ANOVA showed a significant sex-by-diagnosis interaction in total correct score (F(1,711) = 5.090, p = 0.024, η_p ² = 0.007) arising from a significant sex difference between control males and females (p < 0.001, Cohen’s d = 0.47), and an absence of a sex difference between males and females with autism (p = 0.907, d = 0.01); significant case-control differences were observed across sexes, with effect sizes of d = 0.35 in males and d = 0.69 in females. Group-difference patterns fit with the extreme-male-brain (EMB) theory predictions. Eyes test-Empathy Quotient and Eyes test-Autism Spectrum Quotient correlations were significant only in females with autism (r = 0.35, r = -0.32, respectively), but not in the other 3 groups. Support vector machine (SVM) classification based on response pattern across all 36 items classified autism diagnosis with a relatively higher accuracy for females (72.2%) than males (65.8%). Nevertheless, an SVM model trained within one sex generalized equally well when applied to the other sex. Performance on the Eyes test is a sex-independent phenotypic characteristic of adults with autism, reflecting sex-common social difficulties, and provides support for the EMB theory predictions for both males and females. Performance of females with autism differed from same-sex controls more than did that of males with autism. Females with autism also showed stronger coherence between self-reported dispositional traits and Eyes test performance than all other groups.     

The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2) Is Increased in Human Lung Cancer

Objectives

Lung cancer is the leading cause of cancer-related deaths worldwide. Overall 5-year survival has shown little improvement over the last decades. Seven in absentia homolog (SIAH) proteins are E3 ubiquitin ligases that mediate proteasomal protein degradation by poly-ubiquitination. Even though SIAH proteins play a key role in several biological processes, their role in human cancer remains controversial. The aim of the study was to document SIAH2 expression pattern at different levels (mRNA, protein level and immunohistochemistry) in human non-small cell lung cancer (NSCLC) samples compared to surrounding healthy tissue from the same patient, and to analyse the association with clinicopathological features.

Materials and Methods

One hundred and fifty-two samples from a patient cohort treated surgically for primary lung cancer were obtained for the study. Genic and protein expression levels of SIAH2 were analysed and compared with clinic-pathologic variables.

Results

The present study is the first to analyze the SIAH2 expression pattern at different levels (RNA, protein expression and immunohistochemistry) in non-small cell lung cancer (NSCLC). We found that SIAH2 protein expression is significantly enhanced in human lung adenocarcinoma (ADC) and squamous cell lung cancer (SCC). Paradoxically, non-significant changes at RNA level were found, suggesting a post-traductional regulatory mechanism. More importantly, an increased correlation between SIAH2 expression and tumor grade was detected, suggesting that this protein could be used as a prognostic biomarker to predict lung cancer progression. Likewise, SIAH2 protein expression showed a strong positive correlation with fluorodeoxyglucose (2-deoxy-2(¹⁸F)fluoro-D-glucose) uptake in primary NSCLC, which may assist clinicians in stratifying patients at increased overall risk of poor survival. Additionally, we described an inverse correlation between the expression of SIAH2 and the levels of one of its substrates, the serine/threonine kinase DYRK2.

Conclusions

Our results provide insight into the potential use of SIAH2 as a novel target for lung cancer treatment.