Reliability in distinguishing murder from accidental event with current forensic criteria in traumatic head injury.

Discovering a body displaying signs of multiple head trauma requires a thorough examination by the forensic pathologist, and a multidisciplinary approach is recommended. However, determining the manner of death is not always possible. We present a case in which the body of a 60-year-old man was discovered lying face down on the floor of his apartment, partially unclothed, surrounded by blood and vomit, and presenting numerous head injuries. The autopsy concluded that the cause of death was a result of post-traumatic brain injury. Nevertheless, applying current criteria made it challenging to ascertain whether the trauma stemmed from an accidental event or an assault.

[Sleep in a performance artist: Eight days and seven nights sitting inside a metal sculpture]. / Le sommeil d'un performeur de l'extrême. Dormir huit jours et sept nuits, assis, sans bouger, enfermé dans une sculpture.

Sleep in extreme situations has been little studied. The artist Abraham Poincheval (AP) is known for his performances in confined spaces. For his show at the Perrotin Gallery in Paris, he was enclosed for 8days and 7nights in a metal sculpture of his body in a seated position, with his head facing a work by Hans Hartung at the end of a cone system placed in front of his eyes which occluded all other visual stimuli. The interior of the metal structure was not padded and there was no head support. His sleep and internal temperature were continuously recorded using polysomnography (Grael, Compumedics) and an orally swallowed temperature sensitive capsule (Bodycap) with temperature sampling every 2min. AP slept an average of 355.1min/24h, composed of light slow-wave sleep (N1: 47.1min, N2: 192.2min), deep slow-wave sleep (N3: 100.4min), and REM sleep 4,3 % (15.4min). Sleep, although mostly nocturnal, was split into periods of no more than 20min. Deep sleep was therefore remarkably resistant to the uncomfortable experimental conditions, while REM sleep was markedly impaired, lasting only a few short minutes and followed by rapid awakening. This is probably due to the head position within the sculpture which was unsupported, so REM sleep with its inherent muscle atonia led to involuntary head flexion and was impossible to sustain for long. The thermal minimum was between 5:17 a.m. and 6:35 a.m. The amplitude of the core temperature decreased by more than 30 % between the beginning and the end of the protocol. Despite the immobility induced by the confined experimental conditions, there was no desynchronization of circadian rhythms. The sleep time was surprisingly long given the conditions, and slow-wave sleep was relatively preserved with an amount typically found in normal subjects while REM sleep was markedly impaired. Slow-wave sleep is clearly preserved underlying its central role in physical and mental homeostasis. REM sleep is clearly more fragile. The reduction in REM sleep linked to position has been found in a study of sleep in the sitting position in airplanes where loss of muscle tonus in the neck fragments REM sleep. Techniques for selective REM sleep deprivation also use muscle atonia: one of the initial techniques of selective REM sleep deprivation relied on muscle atonia in REM causing a cat to fall from a small perch into water. In man, the lack of head support is clearly a source of REM fragmentation. However in the case of this study, we cannot exclude an effect of other factors, notably the meditative techniques used by the performer to maintain attention on the painting, described as a dream state punctuated by visual hallucinations. Surprisingly, despite physical isolation within the sculpture, AP's biological rhythms remained stable. However, the conditions were not those of complete isolation: noise, the presence of the public in the gallery who occasionally talked to AP through the sculpture, and variations in light during the day were all temporal cues. In addition, a heatwave during the performance raised the temperature in the room with reduced total sleep time on the hottest night. Although the phase of the circadian rhythm measured by the internal temperature did not change, the amplitude fell which is compatible with reduced physical activity. In conclusion, under physically constraining and uncomfortable sleep conditions, deep sleep is maintained while REM sleep is starkly reduced. From a homeostatic point of view, this means that over a short period of time, in a survival situation, energy recovery through deep slow-wave sleep takes priority over REM sleep.

Paradoxical Air Embolism in Spinal Surgery: Case Report and Literature Review / Embolia gasosa paradoxal em cirurgia de coluna: Relato de caso e revisão de literatura

Air embolism (AE) is a subtype of embolism, caused by the entry of air into the vascular system. It is a predominantly iatrogenic complication, and its symptomatic form is severe, although uncommon. In some cases, a venous thrombi may pass into the arterial system through a venous-arterial shunt, characterizing a paradoxical embolism. Here, we describe the case of a previously healthy 44-year-old female who underwent cauda equina decompression and lumbar epidural abscess drainage. The patient suffered a paradoxical AE intraoperatively and died after 4 days. The occurrence of AE in lumbar spine surgeries in the prone position is rare, but the surgical team must be attentive to its clinical signs and quickly institute initial management when necessary.

A embolia gasosa (EG) é um subtipo de embolia, causada pela entrada de ar no sistema vascular. É uma complicação predominantemente iatrogênica e sua forma sintomática é grave, embora incomum. Em alguns casos, um trombo venoso pode migrar para o sistema arterial através de um shunt venoso-arterial, caracterizando uma embolia paradoxal. Aqui, descrevemos o caso de uma mulher de 44 anos, previamente saudável, submetida a descompressão da cauda equina e drenagem de abscesso peridural lombar. A paciente sofreu uma EG paradoxal no intraoperatório e morreu 4 dias depois. A ocorrência de EG em cirurgias da coluna lombar em posição prona é rara, mas a equipe cirúrgica deve estar atenta aos seus sinais clínicos e, quando necessário, instituir o manejo inicial rapidamente.

[Sleep disorders in patients with a neurocognitive disorder]. / Les troubles du sommeil chez les patients atteints d'un trouble neurocognitif.

INTRODUCTION: Sleep disorders are prevalent in patients with a neurocognitive disorder, and diagnosis and treatment in these patients remain challenging in clinical practice. METHODS: This narrative review offers a systematic approach to diagnose and treat sleep disorders in neurocognitive disorders. RESULTS: Alzheimer's disease is often associated with circadian rhythm disorders, chronic insomnia, and sleep apnea-hypopnea syndrome. Alpha-synucleinopathies (e.g., Parkinson's disease and Lewy body dementia) are often associated with a rapid eye movement sleep behavior disorder, restless legs syndrome, chronic insomnia, and sleep apnea-hypopnea syndrome. A focused history allows to diagnose most sleep disorders. Clinicians should ensure to gather the following information in all patients with a neurocognitive disorder: (1) the presence of difficulties falling asleep or staying asleep, (2) the impact of sleep disturbances on daily functioning (fatigue, sleepiness and other daytime consequences), and (3) abnormal movements in sleep. Sleep diaries and questionnaires can assist clinicians in screening for specific sleep disorders. Polysomnography is recommended if a rapid eye movement sleep behavior disorder or a sleep apnea-hypopnea syndrome are suspected. Sleep complaints should prompt clinicians to ensure that comorbidities interfering with sleep are properly managed. The main treatment for moderate to severe obstructive sleep apnea-hypopnea syndrome remains continuous positive airway pressure, as its efficacy has been demonstrated in patients with neurocognitive disorders. Medications should also be reviewed, and time of administration should be optimized (diuretics and stimulating medications in the morning, sedating medications in the evening). Importantly, cholinesterase inhibitors (especially donepezil) may trigger insomnia. Switching to morning dosing or to an alternative drug may help. Cognitive-behavioral therapy for insomnia is indicated to treat chronic insomnia in neurocognitive disorders. False beliefs regarding sleep should be addressed with the patient and their caregiver. The sleep environment should be optimized (decrease light exposure at night, minimize noise, avoid taking vital signs, etc.). Sleep restriction can be considered as patients with a neurocognitive disorder often spend too much time in bed. The need for naps should be assessed case by case as naps may contribute to insomnia in some patients but allow others to complete their diurnal activities. Trazodone (50mg) may also be used under certain circumstances in chronic insomnia. Recent evidence does not support a role for exogenous melatonin in patients with a neucognitive disorder and insomnia. Patients in long-term care facilities are often deprived of an adequate diurnal exposure to light. Increasing daytime exposure to light may improve sleep and mood. Patients with circadian rhythm disorders can also benefit from light therapy (morning bright light therapy in case of phase delay and evening bright light therapy in case of phase advance). Rapid eye movement sleep behavior disorder can lead to violent behaviors, and the sleeping environment should be secured (e.g., mattress on the floor, remove surrounding objects). Medication exacerbating this disorder should be stopped if possible. High dose melatonin (6 to 18mg) or low dose clonazepam (0.125-0.25mg) at bedtime may be used to reduce symptoms. Melatonin is preferred in first-line as it is generally well tolerated with few side effects. Patients with restless legs syndrome should be investigated for iron deficiency. Medication decreasing dopaminergic activity should be reduced or stopped if possible. Behavioral strategies such as exercise and leg massages may be beneficial. Low-dose dopamine agonists (such as pramipexole 0.125mg two hours before bedtime) can be used to treat the condition, but a prolonged treatment may paradoxically worsen the symptoms. Alpha-2-delta calcium channel ligands can also be used while monitoring for the risk of falls. CONCLUSION: Multiple and sustained nonpharmacological approaches are recommended for the treatment of sleep disturbances in patients with neurocognitive disorder. Pharmacological indications remain limited, and further randomized clinical trials integrating a multimodal approach are warranted to evaluate the treatment of sleep disorders in specific neurocognitive disorders.

Comparison of right-to-left shunt characteristics in cryptogenic embolic ischemic stroke and non-cardioembolic ischemic stroke / Comparação das características do shunt direita-esquerda em pacientes com AVC isquêmico criptogênio e AVC não cardioembólico

Abstract Background: Patent foramen ovale (PFO) has been considered a potential mechanism of embolic stroke of undetermined origin. Objective: The aim of the present study was to identify the features of the right-to-left shunt (RLS) in patients with undetermined embolic ischemic stroke and compare them with those of patients with non-cardioembolic ischemic stroke. Methods: A retrospective study was conducted with 168 patients with stroke and RLS separated into the following two groups: the undetermined embolic stroke group (UES group) and non-cardioembolic stroke group (NCES group). All patients were assessed by transcranial Doppler to evaluate the presence and quantification of microembolic signals (MES) at rest and under Valsalva maneuver. Results: Of all patients evaluated in the current study, 96 were included in the UES group and 72 in the NCES group. In the UES group, 65 patients had RLS with ≥10 MES (67.7%), which was higher than that observed in the NCES group (51.4%, p=0.038). According to the moment of the cardiac cycle, 75 patients (78.1%) in the UES group had a positive test at rest compared to 42 (58.3%) in the NCES group (p=0.007). Conclusions: The current study demonstrated that almost 70% of patients with undetermined embolic stroke and PFO presented a large RLS and more than 75% had RLS at rest. These findings suggest that the size of the shunt should be taken into account when evaluating whether PFO could be a possible mechanism underlying cryptogenic stroke.

RESUMO Antecedentes: Uma das potenciais fontes embólicas no acidente vascular cerebral (AVC) de origem indeterminada é o forame oval patente (FOP). Objetivo: O objetivo do presente estudo foi identificar as características do shunt direita-esquerda em paciente com AVC de etiologia indeterminada, presumidamente embólica, e comparar tais características com pacientes apresentando AVC por outras causas não embólicas. Métodos: Trata-se de um estudo retrospectivo com 168 pacientes com AVC e forame oval patente, separados em dois grupos: AVC embólico de etiologia indeterminada e AVC por outras causas não embólicas. Todos os pacientes foram submetidos a Doppler transcraniano, para avaliar a presença de shunt direita-esquerda por meio do teste de embolia paradoxal. Além da quantificação de microbolhas, também foi avaliada a presença de shunt em repouso e sob manobra de Valsalva. Resultado: Do total, 96 pacientes foram incluídos no primeiro grupo (AVC indeterminado) e 72, no segundo grupo (AVC não embólico). No primeiro grupo, 65 pacientes exibiram shunt com passagem de mais de 10 microbolhas (67,5%), enquanto no segundo grupo isso aconteceu em 51,4% (p=0,038) dos casos. Além disso, 75 pacientes (78,1%) do primeiro grupo tiveram teste positivo ao repouso, comparados com 42 pacientes (58,3%) no segundo grupo (p=0,007). Conclusão: O presente estudo demonstrou que até 70% dos pacientes com AVC de etiologia indeterminada e forame oval apresentaram shunts maiores; em mais de 75%, houve passagem de microbolhas ao repouso. Esses achados sugerem que as características do shunt, como quantidade de microbolhas e passagem ao repouso, devem ser levadas em consideração na avaliação do FOP como possível mecanismo subjacente ao AVC.

Paradoxal dyeing affinity's inversion of the connective tissue at Goldner's Masson trichrome staining as a peculiar characteristic of compressed and exsiccated cadaveric skin.

The microscopic examination of a hanging cutaneous furrow, stained with Goldner's Masson trichrome staining, highlighted an abnormal dyeing inversion affinity of the connective tissue - red instead of green - located in the region of maximal cutaneous compression and exsiccation. To identify if this different stainability could be considered as an intrinsic characteristic of all biological tissues compressed and exsiccated, we have assessed different cadaveric skin samples that underwent traumatic detrimental phenomena that can produce such effects. We collected skin fragments from 24 corpses deceased because of gunshot injuries, electrocution, hanging, and heat-induced lesions, sampling the areas directly involved, as well as skin specimens to use as a control. The slides were stained with hematoxylin and eosin and two different protocols of Goldner's Masson trichrome staining (one homemade and one commercial kit). The inversion of the staining affinity of the connective tissue was observed in 83% of the cutaneous samples, using both the Goldner's Masson trichrome staining protocols. This phenomenon was not observed in any of the control cases. Therefore, the inversion of the staining affinity of the connective tissue dyed with Goldner's Masson trichrome staining may represent a histomorphological aspect that must be expected when the skin has been affected by specific detrimental modalities able of producing compression and exsiccation.

Acute arterial occlusion resulting from paradoxical embolism - case report and literature review.

A embolia paradoxal é a transposição de um trombo originário da circulação sistêmica venosa para a arterial através de um defeito cardíaco, mais comumente o forame oval pérvio (FOP). A manifestação mais comum é o acidente cerebrovascular. A oclusão arterial aguda (OAA) é rara, requer alta suspeição diagnóstica e corresponde a menos de 2% de todos casos de embolia arterial. O tromboembolismo pulmonar (TEP) é a causa mais comum de elevação temporária do shunt direita-esquerda em pacientes com FOP e ocorre em pelo menos 60% dos casos de embolia paradoxal. Em 2019, um homem de 27 anos, sem fator para hipercoagulabilidade, deu entrada no Hospital Universitário do ABC, com quadro de OAA grau I Rutherford em membros inferiores secundária a tromboembolismo através de FOP prévio não diagnosticado, associado a trombose venosa profunda de membro inferior direito e TEP bilateral. O manejo incluiu anticoagulação plena e encaminhamento para cirurgia cardíaca.

Oclusão arterial aguda consequente a embolia paradoxal - relato de caso e revisão de literatura / Acute arterial occlusion resulting from paradoxical embolism - case report and literature review

Resumo A embolia paradoxal é a transposição de um trombo originário da circulação sistêmica venosa para a arterial através de um defeito cardíaco, mais comumente o forame oval pérvio (FOP). A manifestação mais comum é o acidente cerebrovascular. A oclusão arterial aguda (OAA) é rara, requer alta suspeição diagnóstica e corresponde a menos de 2% de todos casos de embolia arterial. O tromboembolismo pulmonar (TEP) é a causa mais comum de elevação temporária do shunt direita-esquerda em pacientes com FOP e ocorre em pelo menos 60% dos casos de embolia paradoxal. Em 2019, um homem de 27 anos, sem fator para hipercoagulabilidade, deu entrada no Hospital Universitário do ABC, com quadro de OAA grau I Rutherford em membros inferiores secundária a tromboembolismo através de FOP prévio não diagnosticado, associado a trombose venosa profunda de membro inferior direito e TEP bilateral. O manejo incluiu anticoagulação plena e encaminhamento para cirurgia cardíaca.

Resumo A embolia paradoxal é a transposição de um trombo originário da circulação sistêmica venosa para a arterial através de um defeito cardíaco, mais comumente o forame oval pérvio (FOP). A manifestação mais comum é o acidente cerebrovascular. A oclusão arterial aguda (OAA) é rara, requer alta suspeição diagnóstica e corresponde a menos de 2% de todos casos de embolia arterial. O tromboembolismo pulmonar (TEP) é a causa mais comum de elevação temporária do shunt direita-esquerda em pacientes com FOP e ocorre em pelo menos 60% dos casos de embolia paradoxal. Em 2019, um homem de 27 anos, sem fator para hipercoagulabilidade, deu entrada no Hospital Universitário do ABC, com quadro de OAA grau I Rutherford em membros inferiores secundária a tromboembolismo através de FOP prévio não diagnosticado, associado a trombose venosa profunda de membro inferior direito e TEP bilateral. O manejo incluiu anticoagulação plena e encaminhamento para cirurgia cardíaca.

Efectos del Antecedente de Abuso, Rumiación, Ansiedad y Depresión Sobre la Contracción Paradójica del Puborrectal / Effects of Abuse History, Rumination, Anxiety, and Depression on the Paradoxical Contraction of the Puborectalis Muscle / Efeitos do Antecedente de Abuso, Ruminação, Ansiedade e Depressão sobre a Contração Paradoxal do Puborretal

Resumen El objetivo de este trabajo fue determinar los efectos del antecedente de abuso sexual y emocional, rumiación, ansiedad y depresión sobre la contracción paradójica del puborrectal. Se realizó un estudio de campo con diseño transversal en 118 pacientes. Los resultados de los análisis de regresión demuestran que el antecedente de abuso sexual predice contracción paradójica del puborrectal, depresión y rumiación, además de ejercer efecto indirecto sobre depresión y ansiedad a través de rumiación. El antecedente de abuso emocional predice mayor ansiedad y menor depresión. La rumiación predice ansiedad y depresión. Se sugiere aplicar estos resultados en la práctica y explorar en estudios ulteriores las interrogantes derivadas de este trabajo.

Abstract The objective of this research was to determine the effects of sexual and emotional abuse history, rumination, anxiety, and depression on the paradoxical contraction of the puborectalis muscle. A cross-sectional study was carried out in 118 patients. The results of regression analyses show that a history of sexual abuse predicts paradoxical contraction of the puborectalis muscle, depression, and rumination, besides having an indirect effect on depression and anxiety through rumination. A history of emotional abuse predicts greater anxiety and less depression. The article suggests that these results must be applied in practice and that subsequent studies should explore the questions deriving from this research.

Resumo O objetivo deste trabalho foi determinar os efeitos do antecedente de abuso sexual e emocional, ruminação, ansiedade e depressão sobre a contração paradoxal do puborretal. Realizou-se um estudo de campo com desenho transversal em 118 pacientes. Os resultados das análises de regressão demonstram que o antecedente de abuso sexual prevê a contração paradoxal do puborretal, depressão e ruminação, além de exercer efeito indireto sobre depressão e ansiedade através da ruminação. O antecedente de abuso emocional prevê maior ansiedade e menor depressão. A ruminação prevê ansiedade e depressão. Sugere-se aplicar esses resultados na prática e explorar as interrogantes derivadas deste trabalho em estudos posteriores.

Fractional excretion of electrolytes and paradoxical aciduria in dairy cows with left displaced abomasum / Excreção fracionada de eletrólitos em acidúria paradoxal em vacas leiteiras com deslocamento de abomaso à esquerda

The fractional excretion of electrolytes is used to assess renal function and interpret electrolyte and acid-base imbalances. Left displaced abomasum is a common disorder in dairy cows, which causes hypokalemic, hypochloremic metabolic alkalosis. There is limited information on fractional excretion of electrolytes in cows with displaced abomasum. This study aimed to measure the fractional excretion of sodium, potassium, and chloride and paradoxical aciduria in dairy cows with displaced abomasum. Blood and urine samples were collected from 30 dairy cows before and 24, 48, and 72 h after surgery. The cows were divided into two groups (G1: laparoscopy and G2: laparotomy) with 15 cows each. The concentrations of chloride, sodium, potassium, and creatinine were measured in serum and urine. Urinary pH and packed cell volume were measured. Fractional excretion of sodium, potassium, and chloride and urinary strong ion difference [SID]urine were calculated using published formulas. Cows in both groups showed hypokalemic, metabolic alkalosis before surgery; however, hypochloremia was observed only in G2. Potassium concentration significantly increased 24, 48, and 72 h after surgery in G1 and 48 and 72 h after surgery in G2. There were no significant changes in fractional excretion of sodium, chloride, and potassium and urinary pH and [SID]urine between treatments and time points. Paradoxical aciduria was observed before and 24 h following surgery in G1. Fractional excretion and urinary SID are valuable tools to understand hypochloremic, hypokalemic alkalosis in dairy cows with displaced abomasum, as well as paradoxical aciduria and return of abomasal flux.(AU)

A excreção fracionada de eletrólitos é calculada para verificar a função renal e auxiliar na interpretação de distúrbios eletrolíticos e ácido-base. O deslocamento de abomaso à esquerda é frequente em vacas leiteiras, ocasionado alcalose hipoclorêmica e hipocalêmica. Há pouca informação na literatura sobre excreção fracionada de eletrólitos em vacas com deslocamento de abomaso. Este estudo objetivou mensurar a excreção fracionada de sódio, potássio e cloro e a acidúria paradoxal em vacas leiteiras com deslocamento abomasal. Amostras sanguíneas e urinárias foram coletadas de 30 vacas antes e 24, 48 e 72 horas após operação. As vacas foram divididas em dois grupos (G1: laparoscopia e G2: laparotomia) com 15 animais cada. As concentrações de cloro, sódio, potássio e creatinina foram dosadas no soro e urina. Mensurou-se pH urinário e o hematócrito. A excreção fracionada e diferença de íons fortes urinário [SID]urina foram calculados utilizando fórmulas publicadas. Vacas de ambos os grupos apresentaram alcalose hipocalêmica antes da operação. Não houve alterações significativas na excreção fracionada de sódio, potássio e cloro, no pH urinário e na [SID]urina entre os tratamentos e momentos. Acidúria paradoxal foi observada no G1 antes e 24h após operação. A excreção fracionada e [SID]urina são ferramentas importantes para interpretar a alcalose hipoclorêmica e hipocalêmica em vacas leiteiras com deslocamento de abomaso, como também a acidúria paradoxal e o retorno do fluxo abomasal.(AU)

Paradoxical skin reaction with infliximab treatment / Reação cutânea paradoxal com tratamento com infliximabe

Considering the increased utilization of anti-TNF medications in the treatment of inflammatory and autoimmune diseases, dermatologists should be aware of the possible adverse skin reactions. We describe a case of inverted psoriasis due to the use of infliximab used in the treatment of inflammatory bowel disease. (AU)

Com o aumento do uso de anti-TNF no tratamento de doenças inflamatórias e auto-imunes, os dermatologistas devem estar conscientes da possibilidade de reações cutâneas adversas. Apresentamos um caso de psoríase invertida devido ao uso de infliximab utilizado no tratamento da doença inflamatória intestinal. (AU)

Aproximación físico-química a las alteraciones ácido base en la orina de ovinos con alcalosis hipoclorémica / Physical-chemical approach to acid-base alterations in the urine of sheep with hypochloremic alkalosis / Aproximação físico-química às alterações ácido base na urina de ovinos com alcalose hipoclórica

Resumen La aproximación físico-química para determinar el pH urinario es relativamente nueva y no se ha usado en condiciones patológicas en animales. En el presente artículo, el objetivo principal fue demostrar la validez de esta teoría en la orina de ovinos con alcalosis metabólica hipoclorémica. Se realizó un estudio de tipo experimental para la inducción de la alcalosis metabólica hipoclorémica en ovinos. Durante el periodo de control y de inducción se determinaron en la orina: pH calculado, pH medido, excreción neta de ácido, amonio y diferencia de iones fuertes en la orina (SID) cada 24 h hasta el desarrollo de la aciduria paradójica o el deterioro físico de los sujetos. Se determinó la correlación de Pearson (p) entre el pH medido y calculado a partir del modelo del SID en la orina. Se observó una correlación alta entre el pH urinario medido y el calculado usando el SID calculado con base en la excreción neta de ácido (p = 0,874). La correlación entre SID calculado y pH en orina fue significativa (p = 0,839). Sin embargo, la correlación entre el SID y el pH medido de la orina fue moderada (p = 0,588). Se concluye que existe una alta correlación entre el pH calculado a partir del SID usando la excreción neta de ácido y el pH medido en la orina de ovinos con alcalosis metabólica hipoclorémica. Esto indica que el pH urinario depende fuertemente del SID y, por lo tanto, la reducción en el pH puede ser explicada por la disminución del SID.

Abstract The physical-chemical approach to determine urinary pH is relatively new and has not yet been used in pathological conditions in animals. The main objective of this paper was to demonstrate the validity of this theory in the urine of sheep with hypochloremic metabolic alkalosis. An experimental-type study was conducted to induce hypochloremic metabolic alkalosis in sheep. During the control and induction periods, calculated pH, measured pH, net acid excretion, ammonium and strong ion difference (SID) in urine were examined every 24 hours until development of paradoxical aciduria or physical deterioration of subjects. Pearson's correlation (p) was determined between measured and calculated pH based on SID in urine. A high correlation between measured and calculated urine pH was observed using SID calculated from net acid excretion (p = 0.874). The correlation between calculated SID and urine pH was significant (p = 0.839). However, the correlation between SID and measured urine pH was moderate (p = 0.588). It is concluded that there is a high correlation between pH calculated from SID using net acid excretion and pH measured in the urine of sheep with hypochloremic metabolic alkalosis. This indicates that urine pH depends strongly on SID and, therefore, a reduction in pH can be explained by a decrease in SID.

Resumo A aproximação físico-química para determinar o pH urinário é relativamente nova e não tem sido usado em condições patológicas em animais. Neste artigo, o objetivo principal foi demonstrar a validez desta teoria na urina de ovinos com alcalose metabólica hipoclórica. Realizou-se um estudo de tipo experimental para a indução da alcalose metabólica hipoclórica em ovinos. Durante o período de controle e de indução determinaram na urina: pH calculado, pH medido, excreção neta de ácido, amônio e diferença de íons fortes na urina (SID) cada 24 horas hasta o desenvolvimento da aciduria paradoxal ou a deterioração física dos sujeitos. Determinou-se a correlação de Pearson (p) entre o pH medido e calculado a partir do modelo do SID na urina. Observou-se uma correlação alta entre o pH urinário medido e o calculado usando o SID calculado a partir da ex creção líquida de ácido (p = 0,874). A correlação entre SID calculado e pH em urina foi significativa (p = 0,839). Contudo, a correlação entre o SID e o pH medido da urina foi moderada (p = 0.588). Conclui-se que existe uma alta correlação entre o pH calculado a partir do SID usando a excreção líquida de ácido e o pH medido na urina de ovinos com alcalose metabólica hipoclórica. Isto indica que o pH urinário depende fortemente do SID e, portanto, a redução no pH pode ser explicada pela diminuição do SID.

Paradoxical aortic stenosis: A systematic review. / Estenose aórtica paradoxal ­ revisão sistemática.

Aortic stenosis (AS) is a complex systemic valvular and vascular disease with a high prevalence in developed countries. The new entity "paradoxical low-flow, low-gradient aortic stenosis" refers to cases in which patients have severe AS based on assessment of aortic valve area (AVA) (≤1 cm2) or indexed AVA (≤0.6 cm2/m2), but paradoxically have a low mean transvalvular gradient (<40 mmHg) and a low stroke volume index (≤35 ml/m2), despite preserved left ventricular ejection fraction (≥50%). A search was carried out in the PubMed database on paradoxical AS for the period 2007-2014. A total of 57 articles were included for this review. The prevalence of paradoxical AS ranged from 3% to 35% of the population with severe degenerative AS. It was more frequent in females and in older patients. Paradoxical AS was associated with characteristic left ventricular remodeling as well as an increase in systemic arterial stiffness. It was noted that there may be errors and inaccuracies in the calculation of AVA by the continuity equation, which could erroneously suggest the paradoxical phenotype. There are new diagnostic methods to facilitate the study of AS, such as aortic valve calcium score, valvuloarterial impedance and the longitudinal mechanics of the left ventricle. With regard to its natural history, it is not clear whether paradoxical AS corresponds to an advance stage of the disease or if paradoxical AS patients have a distinct phenotype with specific characteristics. Valve replacement, either surgical or percutaneous, may be indicated in patients with severe and symptomatic paradoxical AS.

Psoriasiform Eruption and Worsening of Pustulosis Palmoplantaris After Treatment with Two Anti-TNF-α Inhibitors, Followed by Successful Treatment with Ustekinumab.

INTRODUCTION: Tumor necrosis factor (TNF)-α inhibitors are widely used for the treatment of inflammatory diseases. One of the side effects of TNF-inhibitors is the development of a psoriatiform eruption, also known as paradoxical psoriasis. In this case report, we describe a patient with this side effect after treatment with adalimumab and etanercept. CASE REPORT: A 45-year-old female was treated with adalimumab 40 mg once every 2 weeks for pustulosis palmoplantaris and psoriatic arthritis. After 2 injections, the patient developed a psoriatiform eruption on her body, which improved after discontinuation of adalimumab but worsened after treatment with etanercept 50 mg twice weekly. Eventually, the patient was treated with topical corticosteroids and ustekinumab 45 mg once every 3 months with a complete remission of the psoriatiform eruption. DISCUSSION: Several case reports and reviews have been published in recent years which describe patients with a psoriatiform eruption after treatment with TNF-α inhibitors. The pathogenesis that causes this psoriatic eruption is unclear. In conclusion, we describe a patient with a psoriatiform eruption after treatment with adalimumab and etanercept. This patient had to discontinue the treatment and eventually had a complete response after treatment with topical corticosteroids and treatment with ustekinumab.

Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats.

Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three-month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days.

The effects of n-acetylcysteine and/or deferoxamine on manic-like behavior and brain oxidative damage in mice submitted to the paradoxal sleep deprivation model of mania.

Bipolar disorder (BD) is a severe psychiatric disorder associated with social and functional impairment. Some studies have strongly suggested the involvement of oxidative stress in the pathophysiology of BD. Paradoxal sleep deprivation (PSD) in mice has been considered a good animal model of mania because it induces similar manic-like behavior, as well as producing the neurochemical alterations which have been observed in bipolar patients. Thus, the objective of the present study was to evaluate the effects of the antioxidant agent's n-acetylcysteine (Nac) and/or deferoxamine (DFX) on behavior and the oxidative stress parameters in the brains of mice submitted to the animal model of mania induced by PSD. The mice were treated for a period of seven days with saline solution (SAL), Nac, DFX or Nac plus DFX. The animals were subject to the PSD protocol for 36 h. Locomotor activity was then evaluated using the open-field test, and the oxidative stress parameters were subsequently evaluated in the hippocampus and frontal cortex of mice. The results showed PSD induced hyperactivity in mice, which is considered a manic-like behavior. In addition to this, PSD increased lipid peroxidation and oxidative damage to proteins, as well as causing alterations to antioxidant enzymes in the frontal cortex and hippocampus of mice. The Nac plus DFX adjunctive treatment prevented both the manic-like behavior and oxidative damage induced by PSD. Improving our understanding relating to oxidative damage in biomolecules, and the antioxidant mechanisms presented in the animal models of mania are important in helping to improve our knowledge concerning the pathophysiology and development of new therapeutical treatments for BD.

Does more sleep matter? Differential effects of NREM- and REM-dominant sleep on sleepiness and vigilance.

We investigated effects of NREM and REM predominant sleep periods on sleepiness and psychomotor performances measured with visual analog scales and the psychomotor vigilance task, respectively. After one week of stable sleep-wake rhythms, 18 healthy sleepers slept 3hours of early sleep and 3hours of late sleep, under polysomnographic control, spaced by two hours of sustained wakefulness between sleep periods in a within subjects split-night, sleep interruption protocol. Power spectra analysis was applied for sleep EEG recordings and sleep phase-relative power proportions were computed for six different frequency bands (delta, theta, alpha, sigma, beta and gamma). Both sleep periods presented with similar sleep duration and efficiency. As expected, phasic NREM and REM predominances were obtained for early and late sleep conditions, respectively. Albeit revealing additive effects of total sleep duration, our results showed a systematic discrepancy between psychomotor performances and sleepiness levels. In addition, sleepiness remained stable throughout sustained wakefulness during both conditions, whereas psychomotor performances even decreased after the second sleep period. Disregarding exchanges for frequency bands in NREM or stability in REM, correlations between outcome measures and EEG power proportions further evidenced directional divergence with respect to sleepiness and psychomotor performances, respectively. Showing that the functional correlation pattern changed with respect to early and late sleep condition, the relationships between EEG power and subjective or behavioral outcomes might however essentially be related to total sleep duration rather than to the phasic predominance of REM or NREM sleep.