IgG4-related hypophysitis: a retrospective cohort study

Purpose: IgG4-related hypophysitis (IgG4-RH) is a rare chronic inflammatory condition of the pituitary gland. This study reports the presentation, management and outcomes for patients with histologically proven IgG4-related hypophysitis. Methods: A prospectively maintained electronic database was searched over a 14-year period from 1 January 2007 to 31 December 2020 at a single academic centre to identify all patients with a histological diagnosis of IgG4-RH. A retrospective case note review from electronic health records was conducted for each case to extract data on their presentation, management and outcomes. Results: A total of 8 patients (5 male) with a median age of 51 years were identified. The most common presenting symptoms were headache (4/8; 50%), fatigue (3/8; 37.5%) and visual impairment (2/8; 25%). Three patients were initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, ultimately all patients underwent transsphenoidal surgery. Post-operative changes included radiological reduction in pituitary mass in all patients that had imaging (7/7; 100%), improvement in vision (1/2; 50%), residual thick pituitary stalk (5/7; 71.4%), persistent anterior hypopituitarism (4/8; 50%) and panhypopopituitarism including diabetes insipidus (3/8; 37.5%). Conclusions: IgG4-RH is an increasingly recognised entity presenting with a variety of symptoms and signs. Clinical presentation is similar to other forms of hypophysitis. It is therefore important to consider IgG4-RH as a differential and to have a low threshold for pituitary biopsy, the diagnostic gold standard. The diagnosis of IgG4-RH will guide decisions for additional workup for IgG4-related disease, multi-disciplinary team involvement and follow-up

Craniopharyngioma in children: trends from a third consecutive single-center cohort study

OBJECTIVE: The management of children with craniopharyngioma has evolved over time, with a trend toward less invasive neurosurgical approaches as surgeons have sought to balance oncological control and treatment-related morbidity. To this end, the aim of this study was to evaluate the safety and effectiveness of the current management of children with craniopharyngioma compared to the previous management methods used at the authors’ treatment center. METHODS: A prospectively maintained database was searched over a 14-year period between January 1, 2005, and December 31, 2018, to identify all children 17 years of age or younger with a new diagnosis of craniopharyngioma. A retrospective case note review was performed for each child to extract data on the presentation, investigation, treatment, and outcome of their illness. Morbidity was assessed in the same fashion as in previous cohorts, according to the following categories: visual loss, pituitary dysfunction, hypothalamic dysfunction, neurological deficits, and cognitive impairment. RESULTS: In total, 59 children were identified with craniopharyngioma during the study period. A total of 92 operations were performed, including cyst drainage (35/92; 38.0%), craniotomy and resection (30/92; 32.6%), and transsphenoidal resection (16/92; 17.4%). Approximately two-thirds of all operations were performed using image guidance (66/92; 71.7%) and one-third were performed using endoscopy (27/92; 29.3%). The majority of children had adjuvant therapy comprising proton beam therapy (18/59; 30.5%) or conventional radiotherapy (16/59; 27.1%). The median follow-up duration was 44 months (range 1–142 months), and approximately one-half of the children had no evidence of residual disease on MRI studies (28/59; 47.5%). Of the remaining 31 children, there was a reduction in the volume of residual disease in 8 patients (8/59; 13.6%), stable residual disease in 18 (18/59; 30.5%), and tumor growth in 5 patients (5/59; 8.5%). There was significantly reduced morbidity (p < 0.05) in all categories in the current cohort compared with our last cohort (1996–2004). CONCLUSIONS: The authors’ institutional experience of pediatric craniopharyngioma confirms a trend toward less invasive neurosurgical procedures, most of which are now performed with the benefit of image guidance or endoscopy. Moreover, the authors have identified an expanding role for more targeted radiotherapy for children with residual disease. These advances have allowed for tumor control comparable to that achieved in previous cohorts, but with significantly reduced morbidity and mortality

Effects of knee joint angle on global and local strains within human triceps surae muscle: MRI analysis indicating in vivo myofascial force transmission between synergistic muscles

Purpose Mechanical interactions between muscles have been shown for in situ conditions. In vivo data for humans is unavailable. Global and local length changes of calf muscles were studied to test the hypothesis that local strains may occur also within muscle for which global strain equals zero. Methods For determination of globally induced strain in m. gastrocnemius in dissected human cadavers several knee joint angles were imposed, while keeping ankle joint angle constant and measuring its muscle-tendon complex length changes. In vivo local strains in both gastrocnemius and soleus muscles were calculated using MRI techniques in healthy human volunteers comparing images taken at static knee angles of 173° and 150°. Results Imposed global strains on gastrocnemius were much smaller than local strains. High distributions of strains were encountered, e.g. overall lengthened muscle contains locally lengthened, as well as shortened areas within it. Substantial strains were not limited to gastrocnemius, but were found also in synergistic soleus muscle, despite the latter muscle-tendon complex length remaining isometric (constant ankle angle: i.e. global strain = 0), as it does not cross the knee. Based on results of animal experiments this effect is ascribed to myofascial connections between these synergistic muscles. The most likely pathway is the neurovascular tract within the anterior crural compartment (i.e. the collagen reinforcements of blood vessels, lymphatics and nerves). However, direct intermuscular transmission of force may also occur via the perimysium shared between the two muscles. Conclusions Global strains imposed on muscle (joint movement) are not good estimators of in vivo local strains within it: differing in magnitude, as well as direction of length change. Substantial mechanical interaction occurs between calf muscles, which is mediated by myofascial force transmission between these synergistic muscles. This confirms conclusions of previous in situ studies in experimental animals and human patients, for in vivo conditions in healthy human subjects. © 2011 Springer-Verlag

Cortical Modulation of the Transient Visual Response at Thalamic Level: A TMS Study

The transient visual response of feline dorsal lateral geniculate nucleus (dLGN) cells was studied under control conditions and during the application of repetitive transcranial magnetic stimulation at 1 Hz (rTMS@1Hz) on the primary visual cortex (V1). The results show that rTMS@1Hz modulates the firing mode of Y cells, inducing an increase in burst spikes and a decrease in tonic firing. On the other hand, rTMS@1Hz modifies the spatiotemporal characteristics of receptive fields of X cells, inducing a delay and a decrease of the peak response, and a change of the surround/center amplitude ratio of RF profiles. These results indicate that V1 controls the activity of the visual thalamus in a different way in the X and Y pathways, and that this feedback control is consistent with functional roles associated with each cell type

Effects of salinity and drought on growth, ionic relations, compatible solutes and activation of antioxidant systems in oleander (Nerium oleander L.)

[EN] Nerium oleander is an ornamental species of high aesthetic value, grown in arid and semi- arid regions because of its drought tolerance, which is also considered as relatively resistant to salt; yet the biochemical and molecular mechanisms underlying oleander¿s stress toler- ance remain largely unknown. To investigate these mechanisms, one-year-old oleander seedlings were exposed to 15 and 30 days of treatment with increasing salt concentratio ns, up to 800 mM NaCl, and to complete withholding of irrigation; growth parameters and bio- chemical markers characteristic of conserved stress-response pathways were then deter- mined in stressed and control plants. Strong water deficit and salt stress both caused inhibition of growth, degradation of photosynthetic pigments, a slight (but statistically signifi- cant) increase in the leaf levels of specific osmolytes, and induction of oxidative stress¿as indicated by the accumulation of malondialdehyde (MDA), a reliable oxidative stress marker ¿accompanied by increases in the levels of total phenolic compounds and antioxidant fla- vonoids and in the specific activities of ascorbate peroxidase (APX) and glutathione reduc- tase (GR). High salinity, in addition, induced accumulation of Na + and Cl - in roots and leaves and the activation of superoxide dismutase (SOD) and catalase (CAT) activities. Apart from anatomical adaptations that protect oleander from leaf dehydration at moderate levels of stress, our results indicate that tolerance of this species to salinity and water deficit is based on the constitutive accumulation in leaves of high concentratio ns of soluble carbohydrates and, to a lesser extent, of glycine betaine, and in the activation of the aforementioned antiox- idant systems. Moreover, regarding specifically salt stress, mechanisms efficiently blocking transport of toxic ions from the roots to the aerial parts of the plant appear to contribute to a large extent to tolerance in Nerium oleanderThis work was financed by internal funds of the Polytechnic University of Valencia to Monica Boscaiu and Oscar Vicente. Dinesh Kumar’s stay in Valencia was financed by a NAMASTE fellowship from the European Union, and Mohamad Al Hassan was a recipient of an Erasmus Mundus pre-doctoral scholarship financed by the European Commission (Welcome Consortium).Kumar, D.; Al Hassan, M.; Naranjo Olivero, MA.; Agrawal, V.; Boscaiu, M.; Vicente, O. (2017). Effects of salinity and drought on growth, ionic relations, compatible solutes and activation of antioxidant systems in oleander (Nerium oleander L.). PLoS ONE. 12(9). doi:10.1371/journal.pone.0185017Se018501712

Integrating Genome-Wide Genetic Variations and Monocyte Expression Data Reveals Trans-Regulated Gene Modules in Humans

One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns—independent component analysis—to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify major trans-acting regulators. We detected three genomic regions significantly associated with co-regulated gene modules. Association of these loci with multiple expression traits was replicated in Cardiogenics, an independent study in which expression profiles of monocytes were available in 758 subjects. The locus 12q13 (lead SNP rs11171739), previously identified as a type 1 diabetes locus, was associated with a pattern including two cis eQTLs, RPS26 and SUOX, and 5 trans eQTLs, one of which (MADCAM1) is a potential candidate for mediating T1D susceptibility. The locus 12q24 (lead SNP rs653178), which has demonstrated extensive disease pleiotropy, including type 1 diabetes, hypertension, and celiac disease, was associated to a pattern strongly correlating to blood pressure level. The strongest trans eQTL in this pattern was CRIP1, a known marker of cellular proliferation in cancer. The locus 12q15 (lead SNP rs11177644) was associated with a pattern driven by two cis eQTLs, LYZ and YEATS4, and including 34 trans eQTLs, several of them tumor-related genes. This study shows that a method exploiting the structure of co-expressions among genes can help identify genomic regions involved in trans regulation of sets of genes and can provide clues for understanding the mechanisms linking genome-wide association loci to disease

A method for real-time classification of insect vectors of mosaic and brown streak disease in cassava plants for future implementation within a low-cost, handheld, in-field multispectral imaging sensor

Background The paper introduces a multispectral imaging system and data-processing approach for the identification and discrimination of morphologically indistinguishable cryptic species of the destructive crop pest, the whitefly Bemisia tabaci. This investigation and the corresponding system design, was undertaken in two phases under controlled laboratory conditions. The first exploited a prototype benchtop variant of the proposed sensor system to analyse four cryptic species of whitefly reared under similar conditions. The second phase, of the methodology development, employed a commercial high-precision laboratory hyperspectral imager to recover reference data from five cryptic species of whitefly, immobilized through flash freezing, and taken from across four feeding environments. Results The initial results, for the single feeding environment, showed that a correct species classification could be achieved in 85–95% of cases, utilising linear Partial Least Squares approaches. The robustness of the classification approach was then extended both in terms of the automated spatial extraction of the most pertinent insect body parts, to assist with the spectral classification model, as well as the incorporation of a non-linear Support Vector Classifier to maintain the overall classification accuracy at 88–98%, irrespective of the feeding and crop environment. Conclusion This study demonstrates that through an integration of both the spatial data, associated with the multispectral images being used to separate different regions of the insect, and subsequent spectral analysis of those sub-regions, that B. tabaci viral vectors can be differentiated from other cryptic species, that appear morphologically indistinguishable to a human observer, with an accuracy of up to 98%. The implications for the engineering design for an in-field, handheld, sensor system is discussed with respect to the learning gained from this initial stage of the methodology development