Thinking Outside the Box: A Case of Persistent Symptomatic Hypomagnesemia.

Although present in a significant number of people, hypomagnesemia is still an undervalued diagnosis. Therefore, its awareness and comprehensive etiological investigation become imperative. Among its multiple possible causes, drug iatrogenesis plays an important and often overlooked role. Here, we present a case of a 78-year-old female with recurrent bouts of severe hypomagnesemia of unknown origin, which, after an extensive study, was determined to be induced by proton pump inhibitors (PPIs). As such, our goal is to raise awareness of the potential risk of this side effect even in monotherapy, as well as to elucidate its underlying mechanisms, which are still not fully understood. Furthermore, it is intended to foster a systematic therapeutic review in these patients and raise discussion about the potential benefits of systematic magnesium monitoring in patients on long-term PPIs.

Extensive gene loss parallels kidney aglomerulism in Syngnathidae.

The eccentric seahorses, seadragons, pipehorses and pipefishes (Syngnathidae) have an aglomerular kidney1. Here, we show that nephron genes2 conserved in Bilateria are secondarily eroded/deleted in Syngnathidae genomes. A transcriptome enrichment analysis suggests the predominance of excretion processes in the Syngnathidae kidney. In a lineage where crypsis and idleness are tightly associated, we propose that aglomerulism evolved as an energy-saving strategy.

A Case of Febrile Polyphagia With an Underlying Paraneoplastic Limbic Encephalitis.

A 57-year-old female with a history of malignant mixed Müllerian tumors of the uterus and ovaries developed a fever of unknown origin and neuropsychiatric symptoms. Her EEG showed slow activity in the left temporal region, and brain magnetic resonance imaging revealed limbic encephalitis, leading to the diagnosis of classic paraneoplastic limbic encephalitis (PLE). During our investigation into the underlying cause of the patient's condition, we conducted a PET-CT scan, which revealed the presence of several hypermetabolic lymph nodes. One of these lymph nodes underwent a biopsy, and the results confirmed the presence of metastatic cells, indicating the likelihood of carcinoma, most probably adenocarcinoma of the gynecological tract. PLE should be considered as one of the differential diagnoses in patients with a history of cancer and acute-to-subacute neuronal and psychiatric dysfunction.

A Challenging Case of Wilson's Disease.

Wilson's disease (WD) is an inherited disorder characterized by the accumulation of copper in various organs, particularly the liver, central nervous system, and cornea. The clinical presentation of WD can vary widely. Diagnosis requires a combination of clinical and biochemical findings. We present a case of a 20-year-old woman who presented to the Emergency Room with progressive motor decline. She exhibited characteristic neurological symptoms and signs, such as hypomimia, bradyphrenia, bradykinesia, dysarthria, sialorrhea, upper limb dystonia, and wing-beating tremor. Ophthalmological examination revealed corneal deposits known as Kayser-Fleischer rings. Laboratory investigations demonstrated low levels of ceruloplasmin and elevated serum copper. Brain MRI showed typical signs of copper deposition in the basal ganglia. The Leipzig criteria were used to confirm the diagnosis. Treatment with penicillamine and zinc acetate resulted in symptom improvement. This case highlights the diverse presentation of WD and the importance of early diagnosis and prompt treatment initiation.

Photoinduced NiH Catalysis with Trialkylamines for the Stereodivergent Transfer Semi-Hydrogenation of Alkynes.

We report a selectivity-switchable nickel hydride-catalyzed methodology that enables the stereocontrolled semi-reduction of internal alkynes to E- or Z-alkenes under very mild conditions. The proposed transfer semi-hydrogenation process involves the use of a dual nickel/photoredox catalytic system and triethylamine, not only as a sacrificial reductant, but also as a source of hydrogen atoms. Mechanistic studies revealed a pathway involving photo-induced generation of nickel hydride, syn-hydronickelation of alkyne, and alkenylnickel isomerization as key steps. Remarkably, mechanistic experiments indicate that the control of the stereoselectivity is not ensuing from a post-reduction alkene photoisomerization under our conditions. Instead, we demonstrate that the stereoselectivity of the reaction is dependent on the rate of a final protonolysis step which can be tuned by adjusting the pKa of an alcohol additive.

Mom and dad are not that different after all: Immune modulation as a prerequisite for the evolution of pregnancy.

Pregnancy, the post-fertilization period when embryos are incubated within the body, is a dynamic multistage process that has convergently evolved in many vertebrates. To increase independence from environmental fluctuations and protect offspring from predation, challenges had to be initially overcome. The most obvious, when considering such an intimate relationship between the parent and its semi-allogenic offspring, was the pressing need to dodge immunity-associated embryo rejection. In mammals, immunological tolerance was found to be dependent on the active modulation of the immune system. Even though supporting much of the current knowledge on vertebrate pregnancy, mammals lack extant transitional stages that could help reconstruct the evolutionary pathway of this fascinatingly complex reproduction mode. In this issue of Molecular Ecology, Parker et al. selected an untraditional model-the seahorse and pipefish family, whose species evolved male pregnancy across an almost continuous gradient of complexity, from external oviparity to internal gestation. By contrasting gene expression profiles of syngnathids with distinct brooding architectures, this study allowed for the observation of subtle evolutionary adaptations, while confirming the existence of remarkable similarities to "female" pregnancy (e.g., the evolution of male pregnancy in pouched species occurred alongside immune downregulation, and inflammation seems vital during early pregnancy stages). In a world where the debate on sex-roles takes centre stage, Parker et al.'s appeasing results hint at the fact that the strongly convergent evolution of vertebrate pregnancy was seemingly unaffected by which sex carries the burden of gestation.

Automated analysis of activity, sleep, and rhythmic behaviour in various animal species with the Rtivity software.

Behavioural studies provide insights into normal and disrupted biological mechanisms. In many research areas, a growing spectrum of animal models-particularly small organisms-is used for high-throughput studies with infrared-based activity monitors, generating counts per time data. The freely available software to analyse such data, however, are primarily optimized for drosophila and circadian analysis. Researchers investigating other species or non-circadian behaviour would thus benefit from a more versatile software. Here we report the development of a free and open-source software-Rtivity-allowing customisation of species-specific parameters, and offering a versatile analysis of behavioural patterns, biological rhythms, stimulus responses, and survival. Rtivity is based on the R language and uses Shiny and the recently developed Rethomics package for a user-friendly graphical interface without requiring coding skills. Rtivity automatically assesses survival, computes various activity, sleep, and rhythmicity parameters, and performs fractal analysis of activity fluctuations. Rtivity generates multiple informative graphs, and exports structured data for efficient interoperability with common statistical software. In summary, Rtivity facilitates and enhances the versatility of the behavioural analysis of diverse animal species (e.g. drosophila, zebrafish, daphnia, ants). It is thus suitable for a broad range of researchers from multidisciplinary fields such as ecology, neurobiology, toxicology, and pharmacology.

McConnell in Shock.

The ideal approach to hemodynamically unstable patients requires the quick identification of the type of shock and its etiology. This can be a challenge in critically ill patients due to the limited information, the wide number of differential diagnosis and the need for fast intervention. Point-of-care ultrasound (POCUS) is a non-invasive, low-cost, real-time and reliable tool used to rapidly and accurately assess hemodynamically unstable patients at the bedside. It can support diagnosis, tailor therapy and guide further workup, especially in patients deemed too unstable to undergo other imaging studies. The authors describe the case of a patient in obstructive shock due to pulmonary embolism, in which McConnell sign was identified by bedside echocardiography, before lab tests and pulmonary computerized tomography angiogram results were obtained.

A drastic shift in the energetic landscape of toothed whale sperm cells.

Mammalian spermatozoa are a notable example of metabolic compartmentalization.1 Energy in the form of ATP production, vital for motility, capacitation, and fertilization, is subcellularly separated in sperm cells. While glycolysis provides a local, rapid, and low-yielding input of ATP along the flagellum fibrous sheath, oxidative phosphorylation (OXPHOS), far more efficient over a longer time frame, is concentrated in the midpiece mitochondria.2 The relative weight of glycolysis and OXPHOS pathways in sperm function is variable among species and sensitive to oxygen and substrate availability.3-5 Besides partitioning energy production, sperm cell energetics display an additional singularity: the occurrence of sperm-specific gene duplicates and alternative spliced variants, with conserved function but structurally bound to the flagellar fibrous sheath.6,7 The wider selective forces driving the compartmentalization and adaptability of this energy system in mammalian species remain largely unknown, much like the impact of ecosystem resource availability (e.g., carbohydrates, fatty acids, and proteins) and dietary adaptations in reproductive physiology traits.8 Here, we investigated the Cetacea, an iconic group of fully aquatic and carnivorous marine mammals, evolutionarily related to extant terrestrial herbivores.9 In this lineage, episodes of profound trait remodeling have been accompanied by clear genomic signatures.10-14 We show that toothed whales exhibit impaired sperm glycolysis, due to gene and exon erosion, and demonstrate that dolphin spermatozoa motility depends on endogenous fatty acid ß-oxidation, but not carbohydrates. Such unique energetic rewiring substantiates the observation of large mitochondria in toothed whale spermatozoa and emphasizes the radical physiological reorganization imposed by the transition to a carbohydrate-depleted marine environment.

Association of Statins With Functional Outcome and 30-Day Mortality in Patients With Intracerebral Hemorrhage.

Aim The effect of statins is well established in cardiac and cerebrovascular diseases. However, its impact on intracerebral hemorrhage (ICH) is unclear. We aim to identify an association of pre-ICH statin treatment and statin use during admission for ICH with functional outcome at discharge and 30-day mortality. Material and methods A retrospective cohort study was held in patients with ICH admitted to our stroke unit over a year period. Demographic characteristics, risk factors and cardiovascular diseases, Glasgow Coma Scale (GCS), National Institutes of Health Stroke Score (NIHSS), systolic blood pressure (SBP) at admission, cholesterol levels and radiologic findings were analyzed to explore the association between pre-ICH and inpatient statin use with outcomes. The primary endpoint was functional outcome defined as modified Rankin Score (mRS) at discharge and 30-day mortality. We performed a univariate analysis and the variables with statistical significance were included in a multivariate analysis to control for confounding covariates. Results The study included 78 patients, 33 (42.31%) had previous statin intake history, of which 13 (39.39%) maintained statin intake during hospitalization. Regarding functional outcome we did not report a statistically significant difference between groups. In the "pre-ICH statin use" group a decreased 30-day mortality (6.06%, p = 0.009) was observed. In this group it was also noted higher antiplatelet medication use (33.33%, p = 0.006), higher GCS at admission (13-15: 84.38%, p = 0.018) and deep ICH (81.82%, p = 0.030). However, 30-day mortality had no impact in multivariate regression (Odds ratio (OR) 4.535, 95% Confidence Interval (CI) = 0.786-26.173, p = 0.091). In the group that maintained statin treatment during hospitalization no deaths were registered (p = 0.020) and there was no association with functional status. Multivariate regression analysis was not performed due to sample size. Conclusion The only association demonstrated in this study was lower 30-day mortality with pre-ICH statin use and continued statin treatment during admission. However, this was not confirmed by multivariate regression analysis. There were no differences between groups concerning cholesterol values, results that can be explained by the pleiotropic and immunomodulatory effect of statins. However, prospective studies are needed to prove the benefit of the statins in ICH.

Strong Sexual Selection Does Not Induce Population Differentiation in a Fish Species with High Dispersal Potential: The Curious Case of the Worm Pipefish Nerophis lumbriciformis (Teleostei: Syngnathidae).

High levels of population differentiation are a common demographic pattern in syngnathids, even at small geographical scales. This is probably the end result of the common life history traits observed within the family, involving limited dispersal capabilities and strong habitat dependency. The worm pipefish, Nerophis lumbriciformis, which displays all these characteristics, also presents an additional variable potentially able to promote population differentiation: high sexual selection intensity, especially at the extremes of its distribution. Nevertheless, an early life pelagic stage, which presumably allows for admixture, could prevent population structuring. Here, we assessed the phylogeography of N. lumbriciformis through the amplification of the cytochrome b, 12S, and 16S rDNA mitochondrial markers as well as the rhodopsin nuclear marker, performed upon 119 individuals. We observed a genetically homogeneous population with indications of extensive gene flow. We tentatively attribute this finding to the dispersal potential of the species' pelagic larvae, supported by marine currents acting as major dispersal vectors. We also detected a signal of expansion towards the poles, consistent with the current climate change scenario. Despite the marked latitudinal differences in the phenotype of reproducing worm pipefish, the absence of clear population structuring suggests that phenotypic plasticity can have a significant role in the expression of sexual selection-related traits.

Nickel-Catalyzed Mono-Selective α-Arylation of Acetone with Aryl Chlorides and Phenol Derivatives.

The challenging nickel-catalyzed mono-α-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-α-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives. The methodology has been extended to the unprecedented coupling of acetone with phenol derivatives. Mechanistic studies allowed the isolation and characterization of key Ni0 and NiII catalytic intermediates. The Josiphos ligand is shown to play a key role in the stabilization of NiII intermediates to allow a Ni0 /NiII catalytic pathway. Mechanistic understanding was then leveraged to improve the protocol using an air-stable NiII pre-catalyst.

Silyl Radical Mediated Cross-Electrophile Coupling of N-Acyl-imides with Alkyl Bromides under Photoredox/Nickel Dual Catalysis.

A photoredox Ni-catalyzed cross-coupling of N-acyl-imides with unactivated alkyl bromides has been developed that enables efficient access to a variety of functionalized alkyl ketones, including unsymmetrical dialkyl ketones, under very mild and operationally practical conditions. The reaction that operates without the need for any preformed carbon nucleophile proceeds via the combination of two different bond activation processes, i.e. Ni-catalyzed imide activation via C(acyl)-N bond cleavage and (TMS)3Si radical-mediated alkyl halide activation via halogen-atom abstraction.

Missed gallstones in the abdominal wall: complication of a laparoscopic cholecystectomy.

Laparoscopic cholecystectomy, like any invasive procedure, is associated with complications. One of them often ignored despite its frequency, as the results of the low morbidity rate is stone spillage. We present a case of a 38 years male, with obesity; that underwent laparoscopic cholecystectomy for an acute cholecystitis. During surgery, gallbladder perforation occurred with stone spillage. An attempt was made for recovery of all stones. However, one month after surgery, the patient complained of abdominal pain in the upper right quadrant and an abscess of the deep abdominal wall was found caused by a missed gallstone. Although the definitive treatment was not immediate, an attempt at antibiotic therapy was made, unsuccessfully. Afterwards, this patient underwent gallstone extraction and removal of foreign body granuloma with complete resolution of the clinical condition.

Reduced sexual size dimorphism in a pipefish population where males do not prefer larger females.

Within a species' distribution, populations are often exposed to diverse environments and may thus experience different sources of both natural and sexual selection. These differences are likely to impact the balance between costs and benefits to individuals seeking reproduction, thus entailing evolutionary repercussions. Here, we look into an unusual population (Baltic Sea) of the broadnosed pipefish, Syngnathus typhle, where males do not seem to select females based on size and hypothesize that this pattern may derive from a reduction in direct benefits to the male. We further hypothesize that if larger females do not persistently secure a higher reproductive success, either through pre- or postcopulatory sexual selection, a decrease in sexual size dimorphism in the Baltic population should be apparent, especially when contrasted with a well-studied population, inhabiting similar latitudes (Swedish west coast), where males prefer larger females. We found that, in the Baltic population, variation in female quality is low. We were unable to find differences in abortion rates or protein concentration in oocytes produced by females of contrasting sizes. Direct benefits from mating with large partners seem, thus, reduced in the Baltic population. We also found no evidence of any postcopulatory mechanism that could favor larger mothers as embryo development was unrelated to female size. While female size can still be selected through intrasexual competition or fecundity selection, the pressure for large female body size seems to be lower in the Baltic. Accordingly, we found a noticeable decrease in sexual size dimorphism in the Baltic population. We conclude that, although far from negating the significance of other selective processes, sexual selection seems to have a decisive role in supporting pipefish sexual size asymmetries.

Do-not-resuscitate and treatment limitation decisions - Six years of experience from a Portuguese General Intensive Care Unit.

OBJECTIVE: Treatment limitation, as well as do-not-resuscitate (DNR) directives, are difficult but important to improve patients' quality of life and minimize dysthanasia. We aimed to study the approach to withholding, withdrawal, and DNR decisions, patients' characteristics, and process documentation in a general Intensive Care Unit (ICU) in Portugal. METHODS: A retrospective analysis of data regarding the limitation of treatment decisions collected from previously-designed forms and complemented by medical record consultation. RESULTS: A total of 1602 patients were admitted to the ICU between 2011 and 2016. DNR decisions were documented in 127 cases (7.9%). Patients with treatment limitations were older and had higher Simplified Acute Physiology Score II. The most frequent diagnosis preceding these decisions was sepsis (52.0%, n = 66); the most common main reason for limiting treatment was a poor prognosis of acute illness. Of the patients to whom a DNR was implemented, 117 (92.1%) died in the ICU (40.1% of the total number of ICU deaths), and hospital mortality was 100%. Participants in these decisions, as well as types of treatment withdrawn and their respective timings, were not registered in medical records. CONCLUSION: Treatment limitation and DNR decisions were relatively common, in line with other Southern European studies, but behind Northern European and North American centers. Patients with these limitations were older and more severely ill than patients without such decisions. Documentation of these processes should be clear and detailed, either in specific forms or computerized clinical records; there is room for improvement in this area.

Do-not-resuscitate and treatment limitation decisions - Six years of experience from a Portuguese General Intensive Care Unit

SUMMARY OBJECTIVE Treatment limitation, as well as do-not-resuscitate (DNR) directives, are difficult but important to improve patients' quality of life and minimize dysthanasia. We aimed to study the approach to withholding, withdrawal, and DNR decisions, patients' characteristics, and process documentation in a general Intensive Care Unit (ICU) in Portugal. METHODS A retrospective analysis of data regarding the limitation of treatment decisions collected from previously-designed forms and complemented by medical record consultation. RESULTS A total of 1602 patients were admitted to the ICU between 2011 and 2016. DNR decisions were documented in 127 cases (7.9%). Patients with treatment limitations were older and had higher Simplified Acute Physiology Score II. The most frequent diagnosis preceding these decisions was sepsis (52.0%, n = 66); the most common main reason for limiting treatment was a poor prognosis of acute illness. Of the patients to whom a DNR was implemented, 117 (92.1%) died in the ICU (40.1% of the total number of ICU deaths), and hospital mortality was 100%. Participants in these decisions, as well as types of treatment withdrawn and their respective timings, were not registered in medical records. CONCLUSION Treatment limitation and DNR decisions were relatively common, in line with other Southern European studies, but behind Northern European and North American centers. Patients with these limitations were older and more severely ill than patients without such decisions. Documentation of these processes should be clear and detailed, either in specific forms or computerized clinical records; there is room for improvement in this area.

RESUMO OBJETIVO Decisões de limitação terapêutica (DLT) e de não reanimação (DNR) são difíceis, mas importantes, visando melhorar a qualidade de vida dos doentes e minimizar distanásia. O objetivo deste estudo foi avaliar a abordagem das DNR e DLT, as características dos doentes e a documentação dessas decisões numa Unidade de Cuidados Intensivos Polivalente (Ucip) em Portugal. MÉTODOS Análise retrospectiva dos dados referentes a DLT e DNR, recolhidos a partir de formulários previamente elaborados e complementados por consulta de processo clínico. RESULTADOS Um total de 1.602 doentes foi internado na Ucip entre 2011 e 2016. DNR foi documentada em 127 casos (7,9%). Doentes com DLT eram mais velhos e tinham um Simplified Acute Physiology Score II mais elevado. O diagnóstico mais frequente que precedeu essas decisões foi sepse (52,0%, n=66); A razão mais comum para limitar o tratamento foi mau prognóstico da doença aguda. Dos doentes nos quais a DNR foi implementada, 117 (92,1%) morreram na Ucip (40,1% do total de óbitos na Ucip) e a mortalidade hospitalar foi de 100%. Os intervenientes nessas decisões, bem como os tipos de tratamento retirados, não foram rotineiramente registrados. CONCLUSÃO As DLT e DNR foram relativamente comuns, em consonância com outros estudos do sul da Europa, mas atrás dos centros do norte da Europa e da América do Norte. Os doentes com essas limitações eram mais velhos e mais gravemente doentes. A documentação dessas decisões deve ser clara e detalhada, seja em formulários específicos, seja em registros clínicos informatizados. Há espaço para melhorias nessa área.

Non-Tuberculous Mycobacteria: Seven-Year Experience of a Tertiary Hospital.

INTRODUCTION: Non-tuberculous mycobacteria are ubiquitous organisms. Precise determination of infection numbers is difficult, since reporting them to public health departments is frequently not mandatory; furthermore, isolating a non-tuberculous mycobacteria does not necessarily translate into disease. The aims of this study were to ascertain non-tuberculous mycobacteria data of a tertiary hospital, determine the incidence and approach to colonization versus disease, and the incidence of predisposing comorbidities. MATERIAL AND METHODS: Retrospective study in a tertiary hospital, involving patients with positive cultural exam for non-tuberculous mycobacteria in any biological sample, from 2010 to 2017. RESULTS: A total of 125 non-tuberculous mycobacteria isolates was identified, corresponding to 96 patients. Of these, 57.4% were male (n = 54); median age was 65 years (interquartile range = [50 - 82]). From these, 60.7% (n = 57) had some degree of immunosuppression, most frequently due to malignant tumour (49.0%) or HIV infection (39.2%). It was found that 29 patients (31.0%) had structural respiratory tract changes. Colonization was defined in 65.6% of patients (n = 63). While 71.0% of non-tuberculous mycobacteria infections were pulmonary, the remaining 29.0% presented as disseminated. According to available clinical records, 60.6% (n = 20) of the presumably infected patients fulfilled American Thoracic Society diagnostic criteria for non-tuberculous mycobacteria disease. DISCUSSION: Several cases of non-tuberculous mycobacteria infection in this study presented as life-threatening, multi-systemic disease, highlighting the importance of accurate diagnosis and timely treatment. Other cases of presumed infection might instead have corresponded to colonization, possibly resulting in futile therapy. CONCLUSION: While there are diagnostic criteria for treatment of non-tuberculous mycobacteria infections, no such guidelines exist to assess colonization. One of the most challenging aspects remains the correct differentiation between colonization and early-stage infection.

Introdução: Micobactérias não-tuberculosas são organismos ubiquitários. A determinação precisa de incidência e prevalência de infecções por estes agentes é difícil, uma vez que na maioria dos países não são de declaração obrigatória e o isolamento de micobactérias não-tuberculosas não traduz obrigatoriamente a presença de doença. Os objectivos do estudo foram a avaliação dos dados epidemiológicos e abordagem de micobactérias não-tuberculosas num hospital terciário, determinar a incidência de colonização versus infecção, e a presença de comorbilidades. Material e Métodos: Estudo retrospetivo num hospital terciário envolvendo doentes com exame cultural positivo para micobactérias não-tuberculosas em qualquer amostra biológica, de 2010 a 2017. Resultados: Foram isoladas 125 micobactérias não-tuberculosas, correspondendo a 96 doentes. Destes, 57,4% era do sexo masculino (n = 54); a mediana de idade era 65 anos [50 - 82], 60,7% encontrava-se imunossuprimidos, mais frequente tumor maligno (49,0%) ou infeção por vírus da imunodeficiência humana (39,2%). Vinte e nove doentes (31,0%) apresentavam alterações estruturais crónicas da árvore traqueo-brônquica. Colonização assintomática foi identificada em 65,6% dos doentes (n = 63). Do total da amostra, 71,0% das infeções por micobactérias não-tuberculosas era pulmonar, e os restantes 29,0% disseminada. De acordo com os registos clínicos disponíveis, 60,6% (n = 20) das infeções presumidas preenchia critérios de diagnóstico da American Thoracic Society. Discussão: Foram identificados vários casos de infeção multi-sistémica grave, sublinhando a importância do diagnóstico e tratamento adequados e atempados. Paralelamente, foram também descritos casos de infeção presumida que poderão ter correspondido apenas a colonizações assintomáticas. Conclusão: Enquanto se encontram publicados critérios de diagnóstico de infeção por micobactérias não-tuberculosas, tal não acontece até à data para avaliar colonizações. Assim, um dos aspectos mais desafiantes da gestão destes casos é a correcta diferenciação entre colonização assintomática e infeção em fase inicial.