Fournier gangrene - would you KISS it?

Fournier gangrene is a disease characterized by necrotizing fasciitis of the perineal and genital region, resulting from synergistic polymicrobiotic infection. Most infections can be localized to a cutaneous, urethral, or rectal source and can culminate in a fulminant sepsis. Current state of the art is systemic broad-spectrum antibiotics and serial aggressive debridement which result in superficial perineal defect of wide dimensions. We compiled all the cases of Fournier gangrene that required reconstruction after debridement in Centro Hospitalar Universitário Lisboa Central from 2018 to 2022. Inclusion criteria were reconstruction for Fournier defects and patients' age 18 to 90 years old. Exclusion criteria were patients who didn't require reconstruction or didn't complete it due to death or transfer to another healthcare institution. Reconstructive procedures and complication rates are reported as whole numbers and percentages of total. The initial search yielded 32 patients. There were 2 (6.2%) patients with defects that healed by secondary intention, 6 (18.7%) with delayed primary closure, 4 (12.5%) with implantation of the testicle in a medial thigh pocket, 12 (37.5%) with skin grafts, 4 (12.5%) with scrotal advancement flaps, 2 (6.2%) with flaps, and 2 (6.2%) with flaps and skin grafts in combination. Four outcomes were evaluated: number of patients, defect size, method of reconstruction, and wound-healing complications. Most reconstructive techniques provide reliable coverage and protection of testicular function with an acceptable cosmetic result. The reconstructive options need to be patient tailored in order to achieve long lasting results with a minimum of postoperative morbidity.

A Model for Cognitive Personalization of Microtask Design.

The study of data quality in crowdsourcing campaigns is currently a prominent research topic, given the diverse range of participants involved. A potential solution to enhancing data quality processes in crowdsourcing is cognitive personalization, which involves appropriately adapting or assigning tasks based on a crowd worker's cognitive profile. There are two common methods for assessing a crowd worker's cognitive profile: administering online cognitive tests, and inferring behavior from task fingerprinting based on user interaction log events. This article presents the findings of a study that investigated the complementarity of both approaches in a microtask scenario, focusing on personalizing task design. The study involved 134 unique crowd workers recruited from a crowdsourcing marketplace. The main objective was to examine how the administration of cognitive ability tests can be used to allocate crowd workers to microtasks with varying levels of difficulty, including the development of a deep learning model. Another goal was to investigate if task fingerprinting can be used to allocate crowd workers to different microtasks in a personalized manner. The results indicated that both objectives were accomplished, validating the usage of cognitive tests and task fingerprinting as effective mechanisms for microtask personalization, including the development of a deep learning model with 95% accuracy in predicting the accuracy of the microtasks. While we achieved an accuracy of 95%, it is important to note that the small dataset size may have limited the model's performance.

Ulcerating stasis dermatitis of the forearm associated with arteriovenous graft and central vein stenosis.

INTRODUCTION: Stasis dermatitis is a pathologic condition of the skin that most commonly occurs in the lower limb, where it is caused by chronic venous insufficiency. Stasis dermatitis of the upper limb is rare. CASE REPORT: A 45-year-old male, resident in Angola, presented to the emergency department with an ulcer encompassing the entire left forearm. Past medical history comprised arterial hypertension and end stage renal disease treated with hemodialysis. Dialysis access consisted of a left brachial-basilic AV graft obtained 4 years before. The patient also reported that a right internal jugular vein catheter was used previously during the maturation of the left brachial-basilic AV graft. Stenosis of the left brachiocephalic vein was documented at angiography. Angioplasty was performed, with complete resolution of the wound 2 months after admission. CONCLUSION: The differential diagnosis of extensive ulcer of the forearm must include neoplasms, cellulitis, and/or deep tissue infection with secondary ulceration, but it is also important to maintain suspicion for venous stasis syndrome as a rare but possible cause of these lesions.

Neuronal cholinergic signaling constrains norepinephrine activity in the heart.

It is well known that cholinergic hypofunction contributes to cardiac pathology, yet, the mechanisms involved remain unclear. Our previous study has shown that genetically engineered model of cholinergic deficit, the vesicular acetylcholine transporter knockdown homozygous (VAChT KDHOM) mice, exhibit pathological cardiac remodeling and a gradual increase in cardiac mass with aging. Given that an increase in cardiac mass is often caused by adrenergic hyperactivity, we hypothesized that VAChT KDHOM mice might have an increase in cardiac norepinephrine (NE) levels. We thus investigated the temporal changes in NE content in the heart from 3-, 6-, and 12-mo-old VAChT mutants. Interestingly, mice with cholinergic hypofunction showed a gradual elevation in cardiac NE content, which was already increased at 6 mo of age. Consistent with this finding, 6-mo-old VAChT KDHOM mice showed enhanced sympathetic activity and a greater abundance of tyrosine hydroxylase positive sympathetic nerves in the heart. VAChT mutants exhibited an increase in peak calcium transient, and mitochondrial oxidative stress in cardiomyocytes along with enhanced G protein-coupled receptor kinase 5 (GRK5) and nuclear factor of activated T-cells (NFAT) staining in the heart. These are known targets of adrenergic signaling in the cell. Moreover, vagotomized-mice displayed an increase in cardiac NE content confirming the data obtained in VAChT KDHOM mice. Establishing a causal relationship between acetylcholine and NE, VAChT KDHOM mice treated with pyridostigmine, a cholinesterase inhibitor, showed reduced cardiac NE content, rescuing the phenotype. Our findings unveil a yet unrecognized role of cholinergic signaling as a modulator of cardiac NE, providing novel insights into the mechanisms that drive autonomic imbalance.

Necrotizing Fasciitis Caused by Photobacterium damselae: The First Case in Portugal.

Necrotizing fasciitis is a severe soft tissue infection with a high mortality rate and therefore requires emergent surgical treatment. Several microorganisms can cause this infection, Photobacterium damselae being one of them, with only eight cases previously published in the literature. We report the first ever case of necrotizing fasciitis, caused by this microorganism, in Portugal. In this case report the patient survived after several debridement procedures and reconstruction of the upper limb with acellular dermal matrix and skin graft. A brief review of the Photobacterium damselae soft tissue infection reports as well as the clinical presentation, diagnosis, pathophysiology and treatment of necrotizing fasciitis can also be found in this paper.

Streptococcus anginosus and Phalangeal Osteomyelitis: An Unusual Presentation.

INTRODUCTION: Osteomyelitis of the hand is a rare entity and almost always occurs after catastrophic injuries. Streptococcus anginosus is a part of the normal microbial flora of the oral cavity and the gastrointestinal tract. It is frequently associated with purulent infections in several anatomic locations but rarely harms bony structures. The occurrence of osteomyelitis of the hand caused by this microorganism is very unusual. CASE REPORT: We report the clinical case of a 58-year-old Caucasian male, ex-smoker, with a medical history of a chronic hepatitis C virus infection, liver cirrhosis, and diabetes mellitus that developed extensive osteomyelitis of the middle and distal phalanx of his right ring finger caused by S. anginosus and needed amputation for infection control. He had suffered a cut with a steel grinder on that finger 2 weeks before coming to the emergency department. He was also had been submitted to a dental procedure (tooth extraction) the exact day before the trauma. We believe that the most likely origin of the osteomyelitis was a transient bacteremia caused by the dental procedure that led to hematogenous seeding of several oral commensal microbes, including S. anginosus, that ended up infecting an area with low immune capacity due to the trauma. CONCLUSION: S. anginosus causes purulent infections in multiple locations and affects more often immunocompromised patients, especially those with cirrhosis and diabetes mellitus. Even though it is not often associated with osteomyelitis, we should have a high level of suspicion if the patient has an intraoral disease or a history of dental or gastrointestinal procedures. The infection is severe, often leading to the need for radical debridements.

Fast and slow-twitching muscles are differentially affected by reduced cholinergic transmission in mice deficient for VAChT: A mouse model for congenital myasthenia.

Congenital myasthenic syndromes (CMS) result from reduced cholinergic transmission at neuromuscular junctions (NMJs). While the etiology of CMS varies, the disease is characterized by muscle weakness. To date, it remains unknown if CMS causes long-term and irreversible changes to skeletal muscles. In this study, we examined skeletal muscles in a mouse line with reduced expression of Vesicular Acetylcholine Transporter (VAChT, mouse line herein called VAChT-KDHOM). We examined this mouse line for several reasons. First, VAChT plays a central function in loading acetylcholine (ACh) into synaptic vesicles and releasing it at NMJs, in addition to other cholinergic nerve endings. Second, loss of function mutations in VAChT causes myasthenia in humans. Importantly, VAChT-KDHOM present with reduced ACh and muscle weakness, resembling CMS. We evaluated the morphology, fiber type (myosin heavy chain isoforms), and expression of muscle-related genes in the extensor digitorum longus (EDL) and soleus muscles. This analysis revealed that while muscle fibers atrophy in the EDL, they hypertrophy in the soleus muscle of VAChT-KDHOM mice. Along with these cellular changes, skeletal muscles exhibit altered levels of markers for myogenesis (Pax-7, Myogenin, and MyoD), oxidative metabolism (PGC1-α and MTND1), and protein degradation (Atrogin1 and MuRF1) in VAChT-KDHOM mice. Importantly, we demonstrate that deleterious changes in skeletal muscles and motor deficits can be partially reversed following the administration of the cholinesterase inhibitor, pyridostigmine in VAChT-KDHOM mice. These findings reveal that fast and slow type muscles differentially respond to cholinergic deficits. Additionally, this study shows that the adverse effects of cholinergic transmission, as in the case of CMS, on fast and slow type skeletal muscles are reversible.

Brain-derived neurotrophic factor mediates neuroprotection against Aß-induced toxicity through a mechanism independent on adenosine 2A receptor activation.

Brain-derived neurotrophic factor (BDNF) promotes neuronal survival through TrkB-FL activation. The activation of adenosine A2A receptors (A2AR) is essential for most of BDNF-mediated synaptic actions, such as synaptic plasticity, transmission and neurotransmitter release. We now aimed at evaluating the A2AR influence upon BDNF-mediated neuroprotection against Aß25-35 toxicity in cultured neurons. Results showed that BDNF increases cell survival and reduces the caspase-3 and calpain activation induced by amyloid-ß (Aß) peptide, in a mechanism probably dependent on PLCγ pathway. This BDNF-mediated neuroprotection is not affected by A2AR activation or inhibition. Moreover neither activation nor inhibition of A2AR, per se, significantly influenced Aß-induced neuronal death on calpain-mediated cleavage of TrkB induced by Aß. In conclusion, these results suggest that, in opposition to the fast synaptic actions of BDNF, the neuroprotective actions of this neurotrophin against a strong Aß insult do not require the activation of A2AR.

An analysis of the myocardial transcriptome in a mouse model of cardiac dysfunction with decreased cholinergic neurotransmission.

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KD(HOM)) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KD(HOM) mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression in mutant hearts, which might contribute to increased ROS levels observed in these cardiomyocytes. In contrast, in another model of cardiac remodeling and autonomic imbalance, induced through chronic isoproterenol treatment to increase sympathetic drive, these genes did not appear to be altered in a pattern similar to that observed in VAChT KD(HOM) hearts. These data suggest the importance of maintaining a fine balance between the two branches of the autonomic nervous system and the significance of absolute levels of cholinergic tone in proper cardiac function.

Análise dos transientes da fluorescência da clorofila a de plantas jovens de Carapa guianensis e de Dipteryx odorata submetidas a dois ambientes de luz / Analysis of chlorophyll a fluorescence transients of young plants of Carapa guianensis and Dipteryx odorata submitted to two light environments

Espécies arbóreas tropicais estão quase sempre sob alta irradiância na Amazônia. O elevado fluxo energético pode ser decisivo para o sucesso ou fracasso no estabelecimento inicial das plantas no campo. O objetivo deste trabalho foi investigar as respostas de plantas jovens de andiroba (Carapa guianensis Aubl) e cumaru (Dipteryx odorata (Aublet) Willd) expostas a dois ambientes de luz (sombra e sol). O experimento foi conduzido em Manaus-AM, Brasil (3º8'S, 59º52'W). As análises dos transientes da fluorescência da clorofila a e os parâmetros relacionados foram obtidos em folhas intactas e saudáveis no período entre 10:00 e 12:00h. A curva OJIP indicou que ambas as espécies expostas à alta irradiância apresentaram fotoinibição após 45 dias de experimento. Plantas de andiroba e cumaru expostas ao sol exibiram menores valores de TRo/ABS (7,17 e 20,4%, respectivamente), ETo/TRo (14,5 e 27,2%, respectivamente) e ETo/ABS (20,6 e 42,2%, respectivamente) e maiores valores de DIo/ABS (26,9 e 43,0%, respectivamente), comparadas com plantas exposta à sombra. Quanto ao fluxo fenomenológico, para a maioria dos parâmetros, menores valores foram observados para ambas as espécies expostas ao sol. Plantas de andiroba e cumaru expostas ao sol exibiram valores menores de PI ABS (63,3 e 78,7%, respectivamente) comparadas com plantas expostas à sombra no final do experimento. Apesar de ambas as espécies terem sofrido com o estresse por alta irradiância, plantas de andiroba apresentaram melhores desempenhos do que plantas de cumaru, sendo, portanto, melhor indicadas para uso em plantio de produção ou de recuperação de áreas degradadas.

Tropical tree species are almost always under high irradiance in the Amazonian. The high energy flux can be decisive for the success or not in the initial establishment in the field. The objective of this study was to investigate the answers of young plants of andiroba (Carapa guianensis Aubl) and cumaru (Dipteryx odorata (Aublet) Willd) exposed to two light environments (shade and sunlight). The experiment was carried in Manaus-AM, Brazil (3º8'S, 59º52'W). Analysis of chlorophyll a fluorescence transients were obtained in intact and healthy leaves between 10:00 to 12:00 am. The curve OJIP indicated that the species high irradiance exposed presented photoinhibition after 45 days of experiment. Andiroba and cumaru plants exposed to sunlight exhibited low values of TRo/ABS (7.17 and 20.4%, respectively), ETo/TRo (14.5 and 27.2%, respectively) and ETo/ABS (20.6 and 42.2%, respectively) and high values of DIo/ABS (26.9 and 43.0%, respectively), compared with plants exposed to the shadow with 45 days of experiment. As for phenomenological flux, most of the parameters, low values were observed for both exposed species in the sunlight. Andiroba and cumaru plants exposed in the sunlight exhibited low values of PIABS (63.3 and 78.7%, respectively) compared with exposed plants to the shadow at the end of the experiment. Although the species have suffered with the stress for high irradiance andiroba specie presented better performance than cumaru being indicated for use in production planting or degraded area restoration.

Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure.

Overwhelming evidence supports the importance of the sympathetic nervous system in heart failure. In contrast, much less is known about the role of failing cholinergic neurotransmission in cardiac disease. By using a unique genetically modified mouse line with reduced expression of the vesicular acetylcholine transporter (VAChT) and consequently decreased release of acetylcholine, we investigated the consequences of altered cholinergic tone for cardiac function. M-mode echocardiography, hemodynamic experiments, analysis of isolated perfused hearts, and measurements of cardiomyocyte contraction indicated that VAChT mutant mice have decreased left ventricle function associated with altered calcium handling. Gene expression was analyzed by quantitative reverse transcriptase PCR and Western blotting, and the results indicated that VAChT mutant mice have profound cardiac remodeling and reactivation of the fetal gene program. This phenotype was attributable to reduced cholinergic tone, since administration of the cholinesterase inhibitor pyridostigmine for 2 weeks reversed the cardiac phenotype in mutant mice. Our findings provide direct evidence that decreased cholinergic neurotransmission and underlying autonomic imbalance cause plastic alterations that contribute to heart dysfunction.

Angiotensin-(1-7) prevents cardiomyocyte pathological remodeling through a nitric oxide/guanosine 3',5'-cyclic monophosphate-dependent pathway.

The renin-angiotensin (Ang) system plays a pivotal role in the pathogenesis of cardiovascular disease, with Ang II being the major effector of this system. Multiple lines of evidence have shown that Ang-(1-7) exerts cardioprotective effects in the heart by counterregulating Ang II actions. The questions that remain are how and where Ang-(1-7) exerts its effects. By using a combination of molecular biology, confocal microscopy, and a transgenic rat model with increased levels of circulating Ang-(1-7) (TGR[A1-7]3292), we evaluated the signaling pathways involved in Ang-(1-7) cardioprotection against Ang II-induced pathological remodeling in ventricular cardiomyocytes. Rats were infused with Ang II for 2 weeks. We found that ventricular myocytes from TGR(A1-7)3292 rats are protected from Ang II pathological remodeling characterized by Ca(2+) signaling dysfunction, hypertrophic fetal gene expression, glycogen synthase kinase 3beta inactivation, and nuclear factor of activated T-cells nuclear accumulation. Moreover, cardiomyocytes from TGR(A1-7)3292 rats infused with Ang II presented increased expression levels of neuronal NO synthase. To provide a signaling pathway involved in the beneficial effects of Ang-(1-7), we treated neonatal cardiomyocytes with Ang-(1-7) and Ang II for 36 hours. Treatment of cardiomyocytes with Ang-(1-7) prevented Ang II-induced hypertrophy by modulating calcineurin/nuclear factor of activated T-cell signaling cascade. Importantly, antihypertrophic effects of Ang-(1-7) on Ang II-treated cardiomyocytes were prevented by N(G)-nitro-l-arginine methyl ester and 1H-1,2,4oxadiazolo4,2-aquinoxalin-1-one, suggesting that these effects are mediated by NO/cGMP. Taken together, these data reveal a key role for NO/cGMP as a mediator of Ang-(1-7) beneficial effects in cardiac cells.