Bovine medicine: Whats´s your diagnosis?

INTRODUCTION: Two Angus calves housed in the Swiss Alps for two months were presented with brisket edema, jugular distension, and diarrhea. Hematological and biochemical examination included elevated concentration of erythrocytes and increased activity of liver enzymes. Ultrasonography revealed small amount of pleural effusion hepatomegaly and congested caudal vena cava. The diagnosis of congestive heart failure secondary to high-altitude disease was confirmed in pathology.

INTRODUCTION: Deux veaux Angus alpés dans les Alpes suisses depuis deux mois ont été présentés avec un œdème du poitrail, une stase jugulaire et de la diarrhée. Les examens hématologiques et biochimiques ont révélé une concentration élevée d'érythrocytes ainsi qu'une augmentation de l'activité des enzymes hépatiques. L'échographie a révélé un petit épanchement pleural, une hépatomégalie et une veine cave caudale congestionnée. Le diagnostic d'insuffisance cardiaque congestive secondaire à un mal des montagnes a été confirmé par la pathologie.

Flowers vs. Devils: plants used against witchcraft in the urbanized Sonora Market, Mexico City / Flores vs Demonios: plantas usadas contra la brujería en el urbanizado Mercado de Sonora, Ciudad de México

Mexican markets embody cultural diversity and offer a wide range of products, serving as hubs for local exchange.In our study at Mexico City's Sonora Market, the country's prominent medicinal market, we explored the use of plant remedies against witchcraft in an urban environment. Through interviews with plant vendors and extensive data collection, we identified 21 plant species from 16 botanical families renowned for their effectiveness in combating sorcery, attracting good luck, and promoting success. Additionally, we documented 14 ailments associated with envy and negative emotions. These remedies involved practices and applications such as cleansings, decoctions, baths, and incense burning, aimed at alleviating afflictions and fostering positive outcomes. Notably, the Sonora Market continues to uphold the tradition of using plant remedies against witchcraft, even in the bustling setting of one of the world's largest cities. This highlights the enduring significance of these practices within Mexican society

Los mercados mexicanos encarnan diversidad cultural y ofrecen numerosos productos, sirviendo como centros de intercambio local. En nuestro estudio en el Mercado de Sonora en la Ciudad de México, el sitio de plantas medicinales más relevante del país, exploramos el uso de plantas contra la brujería en un entorno urbano. A través de entrevistas con locatarios, identificamos 21 especies de plantas pertenecientes a 16 familias botánicas usadas en la lucha contra la brujería, atrayendo buena suerte y promoviendo el éxito. Además, documentamos 14 enfermedades asociadas con la envidia y emociones negativas. Los remedios involucraban prácticas y aplicaciones como limpias, decocciones, baños, incienso, con el objetivo de aliviar dolencias y fomentar resultados positivos. En el Mercado deSonora persiste la tradición de utilizar plantas contra la brujería, incluso en el marco de una de las mayores ciudades del mundo, resaltando la importancia de estas prácticas dentro de la sociedad mexicana.

Recurrent patellar dislocation patients with high-grade J-sign have multiple structural bone abnormalities in the lower limbs.

PURPOSE: To explore the relationship between preoperative J-sign grading and structural bone abnormalities in patients with recurrent patellar dislocation (RPD). METHODS: A retrospective study was conducted on RPD patients over 5 years. Patients were categorised based on J-sign grade into low (J- and J1+), moderate (J2+) and high groups (J3+). Trochlear dysplasia (TD) and osseous structures (femoral anteversion angle [FAA], knee torsion, tibial tuberosity-trochlear groove [TT-TG] distance, Caton-Deschamps index) were assessed and grouped according to risk factor thresholds. The χ2 test was used to compare composition ratio differences of structural bone abnormalities among the groups. RESULTS: A total of 256 patients were included, with 206 (80.5%) females. The distribution of J-sign grade was as follows: 89 knees (34.8%) of low grade, 86 moderate (33.6%) and 81 high (31.6%). Among the five structural bone abnormalities, TD was the most common with a prevalence of 78.5%, followed by increased TT-TG at 47.4%. Excessive tibiofemoral rotation had the lowest occurrence at 28.9%. There were 173 (67.6%) patients who had two or more abnormalities, while 45 (17.6%) had four to five bony abnormalities. Among patients with any bony abnormality, the proportion of high-grade J-sign surpassed 40%. Patients with moderate and high-grade J-sign had more increased FAA and more pronounced patella alta (all p < 0.001). The proportion of excessive knee torsion and TD increased with increasing each J-sign grade, with the more notable tendency in knee torsion (high vs. moderate vs. low-grade: 61% vs. 22% vs 7%, p < 0.001). Furthermore, the higher J-sign grade was also associated with more combined bony abnormalities (p < 0.001). In the high-grade J-sign group, 90.2% of the knees had two or more bony risk factors and 40.7% had four or more, which were significantly higher than the moderate and low-grade J-sign groups (40.7% vs. 11.6% vs. 2.2%, p < 0.001). CONCLUSION: In patients with a high-grade J-sign, over 90% of the lower limbs had two or more structural bone risk factors, and more than 40% had four or more. These proportions were significantly higher compared to knees with low-grade and moderate J-sign. In clinical practice, when treating high-grade patellar mal-tracking, it is important to focus on and correct these strongly correlated abnormal bone structures. LEVEL OF EVIDENCE: Level III.

Optimization of Interleukin-10 incorporation for dendritic cells embedded in Poly(ethylene glycol) hydrogels.

Translational research in biomaterials and immunoengineering is leading to the development of novel advanced therapeutics to treat diseases such as cancer, autoimmunity, and viral infections. Dendritic cells (DCs) are at the center of these therapeutics given that they bridge innate and adaptive immunity. The biomaterial system developed herein uses a hydrogel carrier to deliver immunomodulatory DCs for amelioration of autoimmunity. This biomaterial vehicle is comprised of a poly (ethylene glycol)-4 arm maleimide (PEG-4MAL) hydrogels, conjugated with the immunosuppressive cytokine, interleukin-10, IL-10, and cross-linked with a collagenase-degradable peptide sequence for the injectable delivery of immunosuppressive DCs to an anatomical disease-relevant site of the cervical lymph nodes, for intended application to treat multiple sclerosis. The amount of IL-10 incorporated in the hydrogel was optimized to be 500 ng in vitro, based on immunological endpoints. At this concentration, DCs exhibited the best viability, most immunosuppressive phenotype, and protection against proinflammatory insult as compared with hydrogel-incorporated DCs with lower IL-10 loading amounts. Additionally, the effect of the degradability of the PEG-4MAL hydrogel on the release rate of incorporated IL-10 was assessed by varying the ratio of degradable peptides: VPM (degradable) and DTT (nondegradable) and measuring the IL-10 release rates. This IL-10-conjugated hydrogel delivery system for immunosuppressive DCs is set to be assessed for in vivo functionality as the immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype, which consequently enhances cell viability and optimizes the system's immunomodulatory functionality.

Guideline for standardized approach in the treatment of the Mal de Debarquement syndrome.

Introduction: Mal de Debarquement Syndrome (MdDS) is a debilitating neuro-otological disorder. Patients experience almost continuously a perception of self-motion. This syndrome can be motion-triggered (MT-MdDS), such as on a boat, or occur spontaneously or have other triggers (SO-MdDS) in the absence of such motion. Because the pathophysiological mechanism is unknown, treatment options and symptom management strategies are limited. One available treatment protocol involves a readaptation of the vestibular ocular reflex (VOR). This study assesses the effectiveness of vestibulo-ocular reflex (VOR) readaptation in 131 consecutive patients with a fixed protocol. Methods: We administered 131 treatments involving optokinetic stimulation (OKS) paired with a fixed head roll at 0.167 Hz over two to five consecutive days. Each day, four-minute treatment blocks were scheduled twice in the morning and afternoon. Treatment effectiveness was evaluated through questionnaires and posturography. Results: We observed significant improvements in the visual analog scale (VAS), MdDS symptom questionnaire, and posturography measures from pre- to post-treatment. No significant differences were found in outcome variables between MT- and SO-MdDS onsets. Conclusion: Symptoms improved subjectively and objectively in patients' post-treatment. The overall success rate was 64.1%, with no significant difference between MT (64.2%) and SO (63.3%). This study supports the conclusion that VOR readaptation treatment provides relief for two-thirds of MdDS patients, irrespective of the onset type. Based on consistency in the findings, we propose a standardized method for treatment of MdDS based on the OKS with head roll paradigm.

Photodynamic Therapy for the Treatment of Bowen's Disease: A Review on Efficacy, Non-Invasive Treatment Monitoring, Tolerability, and Cosmetic Outcome.

Bowen's disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3-5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen's disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase.

MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2.

BACKGROUND: MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, by interacting with human papillomavirus (HPV)-encoded oncoproteins, and epigenetically regulating coding gene expression. Hence, we attempted to decipher the impact and underlying mechanisms of MAL downregulation in HPV16-related CaCx pathogenesis, by interrogating the interactive roles of MAL antisense lncRNA AC103563.8, E7 oncoprotein and PRC2 complex protein, EZH2. RESULTS: Employing strand-specific RNA-sequencing, we confirmed the downregulated expression of MAL in association with poor overall survival of CaCx patients bearing HPV16, along with its antisense long noncoding RNA (lncRNA) AC103563.8. The strength of positive correlation between MAL and AC103563.8 was significantly high among patients compared to normal individuals. While downregulated expression of MAL was significantly associated with poor overall survival of CaCx patients bearing HPV16, AC103563.8 did not reveal any such association. We confirmed the enrichment of chromatin suppressive mark, H3K27me3 at MAL promoter, using ChIP-qPCR in HPV16-positive SiHa cells. Subsequent E7 knockdown in such cells significantly increased MAL expression, concomitant with decreased EZH2 expression and H3K27me3 marks at MAL promoter. In silico analysis revealed that both E7 and EZH2 bear the potential of interacting with AC103563.8, at the same binding domain. RNA immunoprecipitation with anti-EZH2 and anti-E7 antibodies, respectively, and subsequent quantitative PCR analysis in E7-silenced and unperturbed SiHa cells confirmed the interaction of AC103563.8 with EZH2 and E7, respectively. Apparently, AC103563.8 seems to preclude EZH2 and bind with E7, failing to block EZH2 function in patients. Thereby, enhanced EZH2 expression in the presence of E7 could potentially inactivate the MAL promoter through H3K27me3 marks, corroborating our previous results of MAL expression downregulation in patients. CONCLUSION: AC103563.8-E7-EZH2 axis, therefore, appears to crucially regulate the expression of MAL, through chromatin inactivation in HPV16-CaCx pathogenesis, warranting therapeutic strategy development.

Unhinged: A Prospective Perspective on Being Unsafe1.

Given the unprecedented events unfolding around the globe over the past four years, psychoanalytic communities near and far have sought to ask and ventured to answer the question: What does psychoanalysis have to offer individuals, and the collective, as a way of seeing and being with the reality of what is? Taking up these questions in such a time as this, feels, perhaps inevitably, unsafe. Sometimes it can feel as if there is a silent and unspoken mandate to ensure safety at all costs when we seek to find a spirit of the depth's response to the spirit of the times. I propose that the work of psychoanalysis is grounded in nothing but the journey through that which is unsafe. This article will take up Ann Ulanov's notion that one's own evil is the hinge door into collective and archetypal evil. To become unhinged means to risk well-formulated understandings, theories, and modalities about being and becoming for the other and instead to allow the other to penetrate that which is unknown in ourselves, upending our well-formed theories and pressing us to take up our own lives in new and unpredictable ways.

Compte tenu des événements sans précédent qui se sont déroulés dans le monde entier au cours des quatre dernières années, les communautés psychanalytiques proches et lointaines ont cherché à poser la question suivante et à y proposer des réponses: qu'est­ce que la psychanalyse peut offrir aux individus, et au collectif, comme moyen de voir et d'être avec la réalité de ce qui est ? Aborder ces questions dans un moment comme celui­ci nous fait nous sentir en danger, et c'est peut­être inévitable. Parfois, on peut avoir le sentiment qu'il y a un décret silencieux et tacite d'assurer la sécurité à tout prix lorsque nous cherchons à trouver une réponse de l'esprit des profondeurs à l'esprit du temps. Je propose que le travail de la psychanalyse n'est fondé sur rien d'autre que le voyage à travers ce qui est dangereux, risqué. C'est, en effet, ce qu'implique la recherche d'une conversation active et vivante avec l'esprit des profondeurs et c'est ce qui distingue le travail de thérapie du travail de psychanalyse. Si nous nous enfermons dans des notions de sécurité, nous resterons liés à des notions similaires d'anonymat analytique et d'innocence, restant inconscients de notre propre implication dans les horreurs qui continuent d'aliéner, d'étouffer et d'isoler ceux qui sont en marge. Cette présentation reprendra la conception d'Ann Ulanov selon laquelle le mal d'une personne est la porte charnière du mal collectif et archétypal. Notre travail, individuellement et collectivement, est de descendre dans ce territoire dangereux à l'intérieur de nous­mêmes pour voir ce qui s'y est passé et ce qui reste à vivre dans les zones d'ombre. Devenir déséquilibré signifie mettre en doute des compréhensions, des théories et des modalités bien formulées sur l'être et le devenir pour l'autre et, à la place, permettre à l'autre de pénétrer ce qui est inconnu en nous­mêmes, bouleversant nos théories bien formées et nous poussant à prendre notre propre vie en main d'une manière nouvelle et imprévisible. En ce sens, la psychanalyse est intrinsèquement une forme d'activisme intérieur et extérieur. Ce qui est proposé ici est un regard sur la façon dont la psychanalyse, déséquilibrée, se déplace au­delà des murs sécurisants et au­delà des murs de la salle de consultation vers le monde au sens large.

Dados los acontecimientos sin precedentes que han tenido lugar en todo el mundo en los últimos cuatro años, las comunidades psicoanalíticas cercanas y lejanas han tratado de preguntarse y han intentado responder a la pregunta: ¿qué tiene el psicoanálisis que ofrecer a los individuos, y al colectivo, en términos de ver y estar con la realidad de lo que acontece? Abordar estas cuestiones en un momento como el actual puede resultar inevitablemente inseguro. A veces puede dar la sensación de que existe un mandato silencioso y tácito de garantizar la seguridad a toda costa cuando tratamos de encontrar una respuesta del espíritu de las profundidades al espíritu de los tiempos. Propongo que el trabajo del psicoanálisis no se basa en otra cosa que en el viaje a través de lo que es inseguro. Esto, de hecho, es lo que implica buscar una conversación activa y viva con el espíritu de las profundidades y es lo que distingue el trabajo de la terapia del trabajo del psicoanálisis. Si nos encerráramos en las nociones de seguridad, seguiríamos limitados por nociones similares de neutralidad analítica e inocencia, permaneciendo inconscientes de nuestra propia implicancia en los horrores que continúan ajenos, encerrando y aislando a aquellos que se encuentran en los márgenes. Esta presentación retomará la noción de Ann Ulanov de que el mal propio es la puerta de entrada al mal colectivo y arquetipal. Nuestro trabajo individual y colectivo es descender a este territorio inseguro dentro de nosotros mismos para ver lo que ocurrió allí y lo que permanece viviendo en las sombras. Perturbarse significa arriesgar comprensiones, teorías y modalidades bien formuladas sobre el ser y el devenir para el otro y, en su lugar, permitir que el otro penetre en lo que es desconocido en nosotros mismos, trastornando nuestras teorías bien formadas y presionándonos para que asumamos nuestras propias vidas de maneras nuevas e impredecibles. De este modo, el psicoanálisis es inherentemente una forma de activismo interior y exterior. Lo que se ofrece es una mirada sobre cómo el psicoanálisis, perturbado, traspasa los muros de la seguridad y va más allá de las paredes del consultorio analítico para adentrarse en el mundo en general.

Hub Genes and Pathways Related to Lemon (Citrus limon) Leaf Response to Plenodomus tracheiphilus Infection and Influenced by Pseudomonas mediterranea Biocontrol Activity.

The lemon industry in the Mediterranean basin is strongly threatened by "mal secco" disease (MSD) caused by the fungus Plenodomus tracheiphlilus. Leaf pretreatments with Pseudomonas mediterranea 3C have been proposed as innovative tools for eco-sustainable interventions aimed at controlling the disease. In this study, by exploiting the results of previously performed RNAseq analysis, WCGNA was conducted among gene expression patterns in both inoculated (Pt) and pretreated and fungus-inoculated lemon plants (Citrus limon L.) (3CPt), and two indicators of fungal infection, i.e., the amount of fungus DNA measured in planta and the disease index (DI). The aims of this work were (a) to identify gene modules significantly associated with those traits, (b) to construct co-expression networks related to mal secco disease; (c) to define the effect and action mechanisms of P. mediterranea by comparing the networks. The results led to the identification of nine hub genes in the networks, with three of them belonging to receptor-like kinases (RLK), such as HERK1, CLAVATA1 and LRR, which play crucial roles in plant-pathogen interaction. Moreover, the comparison between networks indicated that the expression of those receptors is not induced in the presence of P. mediterranea, suggesting how powerful WCGNA is in discovering crucial genes that must undergo further investigation and be eventually knocked out.

o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2.

Toll-like receptor (TLR) innate immunity signalling protects against pathogens, but excessive or prolonged signalling contributes to a range of inflammatory conditions. Structural information on the TLR cytoplasmic TIR (Toll/interleukin-1 receptor) domains and the downstream adaptor proteins can help us develop inhibitors targeting this pathway. The small molecule o-vanillin has previously been reported as an inhibitor of TLR2 signalling. To study its mechanism of action, we tested its binding to the TIR domain of the TLR adaptor MAL/TIRAP (MALTIR). We show that o-vanillin binds to MALTIR and inhibits its higher-order assembly in vitro. Using NMR approaches, we show that o-vanillin forms a covalent bond with lysine 210 of MAL. We confirm in mouse and human cells that o-vanillin inhibits TLR2 but not TLR4 signalling, independently of MAL, suggesting it may covalently modify TLR2 signalling complexes directly. Reactive aldehyde-containing small molecules such as o-vanillin may target multiple proteins in the cell.

Assessing the synergistic effectiveness of intermittent theta burst stimulation and the vestibular ocular reflex rehabilitation protocol in the treatment of Mal de Debarquement Syndrome: a randomised controlled trial.

INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a rare central vestibular disorder characterised by a constant sensation of motion (rocking, swaying, bobbing), which typically arises after motion experiences (e.g. sea, air, and road travel), though can be triggered by non-motion events. The current standard of care is non-specific medications and interventions that only result in mild-to-moderate improvements. The vestibular ocular reflex (VOR) rehabilitation protocol, a specialised form of rehabilitation, has shown promising results in reducing symptoms amongst people with MdDS. Accumulating evidence suggests that it may be possible to augment the effects of VOR rehabilitation via non-invasive brain stimulation protocols, such as theta burst stimulation (TBS). METHODS: The aim of this randomised controlled trial was to evaluate the effectiveness of intermittent TBS (iTBS) over the dorsolateral prefrontal cortex in enhancing the effectiveness of a subsequently delivered VOR rehabilitation protocol in people with MdDS. Participants were allocated randomly to receive either Sham (n = 10) or Active (n = 10) iTBS, followed by the VOR rehabilitation protocol. Subjective outcome measures (symptom ratings and mental health scores) were collected 1 week pre-treatment and for 16 weeks post-treatment. Posturography (objective outcome) was recorded each day of the treatment week. RESULTS: Significant improvements in subjective and objective outcomes were reported across both treatment groups over time, but no between-group differences were observed. DISCUSSION: These findings support the effectiveness of the VOR rehabilitation protocol in reducing MdDS symptoms. Further research into iTBS is required to elucidate whether the treatment has a role in the management of MdDS. TRN: ACTRN12619001519145 (Date registered: 04 November 2019).

Research advances of MAL family members in tumorigenesis and tumor progression (Review).

The myelin and lymphocyte protein (MAL) family is a novel gene family first identified and characterized in 2002. This family is comprised of seven members, including MAL, MAL2, plasmolipin, MALL, myeloid differentiation­associated marker (MYADM), MYADML2 and CMTM8, which are located on different chromosomes. In addition to exhibiting extensive activity during transcytosis, the MAL family plays a vital role in the neurological, digestive, respiratory, genitourinary and other physiological systems. Furthermore, the intimate association between MAL and the pathogenesis, progression and metastasis of malignancies, attributable to several mechanisms such as DNA methylation has also been elucidated. In the present review, an overview of the structural and functional properties of the MAL family and the latest research findings regarding the relationship between several MAL members and various cancers is provided. Furthermore, the potential clinical and scientific significance of MAL is discussed and directions for future research are summarized.

Relations among Memories of Parental Acceptance-Rejection, Psychological (Mal)Adjustment, Forgiveness, and Vengeance among Iranian Adults.

The study investigated relations among adults' memories of parental acceptance-rejection in childhood and adults' current dispositions toward forgiveness and vengeance, as mediated by psychological (mal)adjustment. Data were collected from 258 adults (female = 183, Age range = 17-47 years; Mage = 39; SD = 11.4). Measures used were the short forms of the maternal and paternal Adult Parental Acceptance-Rejection Questionnaires (PARQ), the short form of the Adult Personality Assessment Questionnaire (PAQ), the Heartland Forgiveness Scale (HFS), the Vengeance Scale (VS-10), and a Personal Information Form (PIF). Results showed that maternal and paternal rejection was positively associated with psychological maladjustment and negatively correlated with forgiveness for both men and women. Moreover, psychological maladjustment showed a negative relation with forgiveness and a positive relation with vengeance. Findings revealed that parental (maternal and paternal) rejection was not significantly associated with vengeance for men. However, maternal (not paternal) rejection was significantly associated with a vengeance for women. Path analysis revealed a significant indirect effect of maternal and paternal rejection on forgiveness and vengeance through psychological maladjustment. Results found no significant gender differences in the path analyses. Findings are discussed considering the Iranian culture and religious beliefs. Implications of the results and future research directions are discussed.

Relations of Parental Acceptance-Rejection and Psychological (Mal)Adjustment with Forgiveness and Vengeance among Bangladeshi Young Adults.

The study investigated whether adults' memories of parental acceptance-rejection in childhood predict their current levels of forgiveness and vengeance as mediated by psychological (mal)adjustment. The data were collected from 252 young adults (Women = 137, Men = 115, Age range = 18 - 22 years; Mage = 19.42; SD = 0.99). Measures used were the Adult Parental Acceptance-Rejection Questionnaire (PARQ) short form for fathers and mothers, the Adult Personality Assessment Questionnaire (PAQ) short form for adults, the Heartland Forgiveness Scale (HFS), the Vengeance Scale (VS-10), and the Personal Information Form. Mediation analysis indicated that memories of maternal and paternal rejection predicted vengeance as mediated by psychological maladjustment among both men and women. Further, women's and men's memories of parental (both maternal and paternal) acceptance predicted forgiveness as mediated by psychological adjustment.

Correlato neurobiológico de los síntomas premotores del parkinson: el origen en la teoría de Braak / Neurobiological correlate of parkinson's premotor symptoms: the origin in Braak's theory / Correlação neurobiológica dos sintomas pré-motores de parkinson: a origem na teoria de Braak

El diagnóstico de enfermedad de Parkinson (ED) se basa en las principales manifestaciones motoras: bradicinesia en combinación con temblor en reposo, rigidez o ambos. Cuando se realiza el diagnóstico basado en la sintomatología motora clínica típica ya se han perdido hasta el 60 % de las neuronas dopaminérgicas de la sustancia negra pars compacta mesencefálica. La identificación de los síntomas premotores son un marcador temprano para sospechar la aparición futura de la enfermedad, así como su progresión y gravedad. La hipótesis sobre la patogénesis que mejor expone la progresión de la enfermedad es la teoría de Braak. Esta se basa en la aparición y presencia de cuerpos de Lewy en diferentes estructuras anatómicas, las cuales representadas en cada uno de sus seis estadios y podrían ser la explicación biológica de los síntomas premotores, motores y no motores. La detección temprana de los síntomas premotores puede tener repercusiones positivas en el enfoque, seguimiento, diagnóstico y tratamiento de la EP. El propósito de este artículo es identificar las aproximaciones neurológicas descritas por la teoría de Braak para los síntomas premotores de la enfermedad de Parkinson de acuerdo con la literatura publicada en los últimos 20 años.

The diagnosis of Parkinson's disease (PD) is based on the main motor manifestations: bradykinesia in combination with tremor at rest, rigidity, or both. When the diagnosis is made based on typical clinical motor symptoms, up to 60 % of the dopaminergic neurons of the mesencephalic substantia nigra pars compacta have already been lost. The identification of premotor symptoms is an early marker to suspect the future appearance of the disease, as well as its progression and severity. The hypothesis about the pathogenesis that best exposes the progression of the disease is Braak's theory. It is based on the appearance and presence of Lewy bodies in different anatomical structures, which are represented in each of its six stages and could be the biological explanation biological of premotor, motor, and non-motor symptoms. Early detection of premotor symptoms can have positive repercussions in the approach, follow-up, diagnosis and treatment of PD. The purpose of this article is to identify the neurological approaches described by Braak's theory for the premotor symptoms of Parkinson's disease according to the literature published in the last 20 years.

O diagnóstico da doença de Parkinson (DP) baseia-se nas principais manifestações motoras: bradicinesia combinada com tremor de repouso, rigidez ou ambos. Quando o diagnóstico é feito com base em sintomas clínicos motores típicos, até 60% dos neurônios dopaminérgicos da substância negra pars compacta mesencefálica já foram perdidos. A identificação de sintomas pré-motores é um marcador precoce para suspeitar do futuro aparecimento da doença, bem como da sua progressão e gravidade. A hipótese sobre a patogênese que melhor expõe a progressão da doença é a teoria de Braak. Isto se baseia no aparecimento e presença de corpos de Lewy em diferentes estruturas anatômicas, que estão representados em cada uma de suas seis etapas e podem ser a explicação biológica dos sintomas pré-motores, motores e não motores. A detecção precoce de sintomas pré-motores pode repercutir positivamente na abordagem, acompanhamento, diagnóstico e tratamento da DP. O objetivo deste artigo é identificar as abordagens neurológicas descritas pela teoria de Braak para os sintomas pré-motores da doença de Parkinson de acordo com a literatura publicada nos últimos 20 anos.

Derotational distal femoral osteotomy improves subjective function and patellar tracking after medial patellofemoral ligament reconstruction in recurrent patellar dislocation patients with increased femoral anteversion: A systematic review and meta-analysis.

PURPOSE: The purpose of this study is to systematically review and quantitatively analyse the clinical outcomes of combined derotational distal femoral osteotomy (D-DFO) and medial patellofemoral ligament reconstruction (MPFL-R) in the treatment of recurrent patellar dislocation (RPD) with increased femoral anteversion angle (FAA). METHODS: This study was performed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the Methodological Quality Of Systematic Reviews) Guidelines. PubMed, Embase, Web of Science and Cochrane Library databases were searched to identify studies reporting clinical outcomes of combined D-DFO and MPFL-R in RPD patients with increased FAA. Data on patient-reported outcome measures, radiological parameters, patellar tracking as revealed by J-sign and complications were extracted based on the inclusion criteria. The Methodological Index for Non-Randomized Study score was used for quality assessment. Review Manager and R statistical software were used to perform the statistical analysis. RESULTS: Eleven studies with a total of 569 knees in 553 patients were included. Patients were predominantly female (79%). The weighted mean of FAA decreased from 33.6° to 13.0° (weighted mean difference = 20.59; p < 0.00001) after the combined procedure. Significant improvements (p < 0.00001) were identified in the Lysholm score (weighted mean: 55.5 vs. 80.4), International Knee Documentation Committee (IKDC) score (weighted mean: 52.8 vs. 78.6) and Kujala score (weighted mean: 54.5 vs. 80.6). The incidence of residual J-sign ranged from 14.3% to 38.3% with an overall pooled rate of 28.2% (95% confidence interval = 22.8%-33.6%). The overall redislocation rate was 1.1%. No patients experienced surgical site infection or bone nonunion. Two studies compared the clinical outcomes of MPFL-R with and without D-DFO. Compared with isolated MPFL-R, the combined procedure yielded a better Lysholm score (weighted mean: 84.9 vs. 79.3, p < 0.0001), IKDC score (weighted mean: 84.1 vs. 79.9, p = 0.001), Kujala score (weighted mean: 84.3 vs. 79.4, p < 0.0001) and a lower residual J-sign rate (26/97 [26.8%] vs. 44/105 [41.9%], p = 0.02), respectively. CONCLUSION: The combination of D-DFO and MPFL-R led to improved clinical outcomes and a low redislocation rate in patients with RPD and increased FAA. Additional D-DFO can achieve more favourable results in subjective function and patellar tracking than isolated MPFL-R in the setting of excessive FAA. LEVEL OF EVIDENCE: Level IV.

Relations between Parental Acceptance-Rejection and Forgiveness/Vengeance as Mediated by Psychological Adjustment among Egyptian Adults.

The study investigated relations among parental (maternal and paternal) acceptance-rejection and dispositions toward forgiveness and vengeance, as mediated by psychological (mal)adjustment. Data were collected using convenience sampling from 341 adults (87% females) ranging from 18 years to above 52 years old. Measures used were short forms of the maternal and paternal Adult Parental Acceptance-Rejection Questionnaires (PARQ) to investigate recollections of parental acceptance-rejection, the short form of the Adult Personality Assessment Questionnaire (PAQ) to evaluate which participants were psychologically (mal)adjusted, the Heartland Forgiveness Scale (HFS), the Vengeance Scale (VS-10) to investigate levels of forgiveness and vengeance respectively, and a Personal Information Form (PIF). The results indicated that participants perceived significant signs of paternal rejection and substantial maternal acceptance during childhood. Men and women self-reported fair psychological adjustment. Women reported having no disposition toward vengeance, whereas men slightly leaned toward vengeance. Participants were equally likely to be unforgiving as forgiving. Psychological adjustment mediated the relations between maternal acceptance (but not paternal acceptance) and forgiveness among men and women. Psychological maladjustment mediated the relations between maternal rejection and vengeance among women, but not men. Psychological maladjustment did not mediate relations between paternal rejection and vengeance. Limitations and implications of the findings are discussed.

In silico mutation of aromatic with aliphatic amino acid residues in Clostridium perfringens epsilon toxin (ETX) reduces its binding efficiency to Caprine Myelin and lymphocyte (MAL) protein receptors.

Enterotoxaemia (ET) is a severe disease that affects domestic ruminants, including sheep and goats, and is caused by Clostridium perfringens type B and D strains. The disease is characterized by the production of Epsilon toxin (ETX), which has a significant impact on the farming industry due to its high lethality. The binding of ETX to the host cell receptor is crucial, but still poorly understood. Therefore, the structural features of goat Myelin and lymphocytic (MAL) protein were investigated and defined in this study. We induced the mutations in aromatic amino acid residues of ETX and substituted them with aliphatic residues at domains I and II. Subsequently, protein-protein interactions (PPI) were performed between ETX (wild)-MAL and ETX (mutated)-MAL protein predicting the domain sites of ETX structure. Further, molecular dynamics (MD) simulation studies were performed for both complexes to investigate the dynamic behavior of the proteins. The binding efficiency between 'ETX (wild)-MAL protein' and 'ETX (mutated)-MAL protein complex' interactions were compared and showed that the former had stronger interactions and binding efficiency due to the higher stability of the complex. The MD analysis showed destabilization and higher fluctuations in the PPI of the mutated heterodimeric ETX-MAL complex which is otherwise essential for its functional conformation. Such kind of interactions with mutated functional domains of ligands provided much-needed clarity in understanding the pre-pore complex formation of epsilon toxin with the MAL protein receptor of goats. The findings from this study would provide an impetus for designing a novel vaccine for Enterotoxaemia in goats.Communicated by Ramaswamy H. Sarma.

[Treatment of therapy-resistant verruca plantaris with laser-assisted photodynamic therapy (PDT) with methyl aminolevulinate (MAL)]. / Therapie von behandlungsresistenten Mosaikwarzen mittels laserassistierter photodynamischer Therapie (PDT) mit Methylaminolävulinat (MAL).

Mosaic warts are a type of verruca vulgaris that occur almost exclusively on the soles of the feet. They are particularly known for their treatment resistance and high recurrence rate. Laser-assisted drug delivery (LADD) photodynamic therapy (PDT) with methyl aminolevulinate (MAL) offers a low pain treatment option with hardly any side effects in therapy-resistant cases of verruca plantaris. Pretreatment with an ablative fractional laser is especially important to obtain penetration of MAL through the human papillomavirus (HPV)-infected skin layer.