Apeced in Turkey: a case report and insights on genetic and phenotypic variability

APECED is a rare monogenic recessive disorder caused by mutations in the AIRE gene. In this manuscript, we report a male Turkish patient with APECED syndrome who presented with chronic mucocutaneous candidiasis associated with other autoimmune manifestations developed over the years. The presence of the homozygous R257X mutation of the AIRE gene confirmed the diagnosis of APECED syndrome. We further performed literature review in 23 published Turkish APECED patients and noted that Finnish major mutation R257X is common in Turks. In particular, we assessed retrospectively how often the Ferre/Lionakis criteria would have resulted in earlier diagnosis in Finns, Sardinians and Turks in respect to the classic criteria. Since an earlier diagnosis could have been possible in 18.8% of Turkish, in 23.8% of Sardinian and 38.55% of Finnish patients we reviewed from literature, Ferre/Lionakis criteria could indeed allow in future earlier initiation of immunomodulatory treatments, if found effective in future studies

A novel homozygous mutation of the AIRE gene in an APECED patient from Pakistan: case report and review of the literature

Autoimmune-poly-endocrinopathy-candidiasis-ectodermal-dystrophy syndrome (APECED) is a rare monogenic recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene. Criteria for the diagnosis of APECED are the presence of two of the following disorders: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CHP), and Addison's disease. APECED develops at high incidence in Finns, Sardinians, and Iranian Jews and presents with a wide range of clinical phenotypes and genotypes. In this manuscript, we report the clinical, endocrinological, and molecular features of a 16-year-old female patient from Pakistan living in Italy and presenting the major APECED clinical manifestations CMC, CHP, and primary adrenal insufficiency. Premature ovarian failure, chronic bronchopneumopathy, vitiligo, Hashimoto's thyroiditis emerged as associated diseases. In our patient, AIRE gene screening revealed the novel c.396G > C (p. Arg132Ser; p. R132S) mutation in homozygosity thus confirming APECED diagnosis. This is the first reported mutation within the nuclear localization signal (NLS) that is associated with APECED. The NLS mutation affects the nuclear import of classical transcription factors through nuclear pore by recognition of nuclear import receptors, the importin a molecules. By displaying crystal structures of the peptide containing the KRK basic residue cluster bound to a importins, we show that p. R132S replacement in 131-KRK-133 does not reproduce these interactions. Thus, we propose that the novel mutation exerts its pathogenetic effect by impairing the nuclear import of the Aire protein. The present case report is added to a limited series of Pakistani APECED patients who we reviewed from the scientific literature, mostly diagnosed on clinical findings

Satellites and the climate crisis: what are we orbiting towards?

On World Humanitarian Day, Alice Pellegrino, Ria Sen, and Federica Angeletti look at the humanitarian development potential of satellite technology, especially its ability to improve disaster and climate risk management. They discuss specific ways in which satellites can be used to manage disaster and climate risk, together with the current and future evolution of the satellite industry

An unusual case of loss of consciousness: when an epileptic brain let the heart slow down

The differential diagnosis of an episode of transient loss of consciousness can be sometimes very tricking, in particular when symptoms peculiar of syncope are mixed with focal neurological symptoms. We report the case of a 54-year-old woman who suddenly claimed, during a polygraphic recording (electroencephalography/electrocardiogram), a feeling of fear and tachycardia followed by loss of consciousness and then a tonic posturing of the left limbs. Polygraphic recording showed a critical electroencephalographic pattern starting from left temporo-zygomatic channels followed after few seconds by a sudden slowing of cortical background activity associated with an episode of asystole, as witnessed simultaneously by electrocardiogram. Muscular activity covered electroencephalographic activity of following minutes. This case provides an opportunity to highlight the existence of rare conditions such as ictal arrhythmias which should be considered in the differential diagnosis of episodes of transient loss of consciousness in particular when dysautonomic and neurological symptoms are intermingled. Autonomic symptoms (vomiting, tachycardia, cyanosis, bradycardia and asystole) may be also more frequent in idiopathic (more rarely symptomatic) epilepsies of childhood (Panayiotopoulos syndrome)

Anterolateral Ligament of the Knee: Back to the Future in Anterior Cruciate Ligament Reconstruction

Although the importance of the anterolateral stabilizing structures of the knee in the setting of anterior cruciate ligament (ACL) injuries has been recognized since many years, most of orthopedic surgeons do not take into consideration the anterolateral structures when performing an ACL reconstruction. Anatomic single or double bundle ACL reconstruction will improve knee stability, but a small subset of patients may experience some residual anteroposterior and rotational instability. For this reason, some researchers have turned again towards the anterolateral aspect of the knee and specifically the anterolateral ligament. The goal of this review is to summarize the existing knowledge regarding the anterolateral ligament of the knee, including anatomy, histology, biomechanics and imaging. In addition, the most common anterolateral reconstruction/tenodesis techniques are described together with their respective clinical outcomes

Electro-membrane Processes for the Green Hydrogen Production

Since the last century, humanity has been facing challenging scenarios, like global warming, environmental pollution and the dramatic increase in energy demand. In this framework, green hydrogen has been identified as the most promising energy vector to achieve carbon neutrality. With this respect, the idea of the present work is to combine the Reverse Electrodialysis (RED) membrane process with hydrogen production. Experimental RED tests were carried out by feeding the unit with different concentrated solutions to study the process performance. Collected results suggest that this approach is a viable way to produce hydrogen with high faradic efficiencies, up to a maximum of 99 %, highlighting also the technology advantage of producing hydrogen by exploiting the salinity gradient energy, thus leading to a production with Specific Energy Consumption close to zero

FGF9 – Nodal signaling negatively control meiotic entry of postnatal male germ cells

Fibroblast growth factor 9 (FGF9) produced by the somatic cells of the testis acts directly on germ cells to inhibit meiosis by upregulating levels of the RNA binding protein Nanos2, both in fetal and postnatal gonad [1]. Several studies have recently demonstrated that the anti-meiotic effect of FGF9 in the fetal testis is mediated by Nodal, a member of the TGF-Beta morphogen family. In fetal male germ cells FGF9 upregulates Cripto, which is a Nodal co-receptor, making these cells unable to enter meiosis [2]. However it is currently unknown how FGF9 acts postnatally to inhibit entry into meiosis of male mitotic germ cells. We first investigated which was the signal transduction pathway activated by FGF9 on postnatal mouse spermatogonia. We found that FGF9 signaling is dependent on ERK but not on AKT activation, which is instead triggered by Kit ligand (an inducer of meiotic entry that cooperates with retinoic acid). By qRT-PCR we found that Nodal and Cripto are expressed in postnatal spermatogonia and that FGF9 (but not Kit ligand) treatment promotes their upregulation. By western blot we found that phospho-Smad2, an indicator of active Nodal signaling, is increased in spermatogonia upon FGF9 treatment, suggesting that Nodal mediates FGF9 action also in postnatal male germ cells

Nonconvulsive Seizures and Dementia: A Case Report

Nonconvulsive status epilepticus (NCSE) is a severe medical condition that shows increased incidence in the elderly and is frequently underdiagnosed because of its pleomorphic presentation. We report an NCSE in a 76-year-old woman affected by dementia with acute change of cognitive status and behavior. Intravenous diazepam solved clinical and electroencephalographic manifestations. Neuropsychological assessment after NCSE conclusion showed impairment of several fields that remained unchanged at 3-month followup. NCSE should be considered when sudden and transient cognitive fluctuations appear in the elderly. Epileptic events in dementia occur frequently and are often underrecognized; this could be a misleading factor when considering a quick progression of mnesic performances. Moreover, recent findings both in animal models and in humans demonstrated the deep link between epilepsy and dementia, also supporting the hypothesis that epileptiform activity could contribute to cognitive impairment