Differences in Tau Seeding in Newborn and Adult Wild-Type Mice.

Alzheimer's disease (AD) and other tauopathies are common neurodegenerative diseases in older adults; in contrast, abnormal tau deposition in neurons and glial cells occurs only exceptionally in children. Sarkosyl-insoluble fractions from sporadic AD (sAD) containing paired helical filaments (PHFs) were inoculated unilaterally into the thalamus in newborn and three-month-old wild-type C57BL/6 mice, which were killed at different intervals from 24 h to six months after inoculation. Tau-positive cells were scanty and practically disappeared at three months in mice inoculated at the age of a newborn. In contrast, large numbers of tau-positive cells, including neurons and oligodendrocytes, were found in the thalamus of mice inoculated at three months and killed at the ages of six months and nine months. Mice inoculated at the age of newborn and re-inoculated at the age of three months showed similar numbers and distribution of positive cells in the thalamus at six months and nine months. This study shows that (a) differences in tau seeding between newborn and young adults may be related to the ratios between 3Rtau and 4Rtau, and the shift to 4Rtau predominance in adults, together with the immaturity of connections in newborn mice, and (b) intracerebral inoculation of sAD PHFs in newborn mice does not protect from tau seeding following intracerebral inoculation of sAD PHFs in young/adult mice.

Risk factors for the need of surgical treatment of a first recurrent lumbar disc herniation.

PURPOSE: A recurrent lumbar disc herniation (RLDH) is the most prevalent cause for new radicular pain after surgery for disc herniation-induced sciatica. Reported risk factors include age, gender and smoking, while its surgical treatment is associated to a higher rate of complications and costs. The purpose of this study is to identify factors that increase the risk of requiring surgical treatment for a first RLDH in workers' compensation patients. METHODS: Nested case-control: 109 patients operated for an RLDH (cases) between June 1st 1994 and May 31st 2011 (minimum follow-up 1 year) and 109 randomly selected patients operated for a first disc herniation with no recurrence during the study period (controls). Age, gender, smoking status, type of work and MRI characteristics of the index herniation were statistically evaluated as potential risk factors. RESULTS: Patient's age of less than 35 years (p = 0.001) and a subligamentous herniation (p < 0.05) at the time of the index surgery were identified as risk factors for requiring surgical treatment of a first RLDH. No statistical differences were observed between both groups regarding the other evaluated variables. CONCLUSION: A subligamentous disc herniation and patient's age inferior to 35 years at the time of the first surgery are risk factors for requiring surgical treatment of a first RLDH among workers' compensation patients.

Posteromedial Submeniscal Arthrotomy and Fixation with a Posteromedial Rim Plate in a Comminuted Medial Tibial Plateau Fracture.

Medial tibial plateau fractures generally present as simple metaphyseal fractures; however, certain cases may present as comminuted articular fractures. Medial and posteromedial anatomical plates have traditionally been used for their management; nevertheless, not all cases can be successfully managed using these implants. We present a comminuted posteromedial Schatzker type VI tibial plateau fracture case. Direct visualization and subsequent fixation using a posteromedial rim plate were achieved through a posteromedial approach and submeniscal arthrotomy. The adequate joint reduction and the obtained stability allowed satisfactory clinical and radiological outcomes. This variation of the classic posteromedial approach and the use of a posteromedial rim plate provide an alternative when facing comminuted medial tibial plateau fractures.

A systematic review and meta-analysis of thigmotactic behaviour in the open field test in rodent models associated with persistent pain.

Thigmotaxis is an innate predator avoidance behaviour of rodents. To gain insight into how injury and disease models, and analgesic drug treatments affect thigmotaxis, we performed a systematic review and meta-analysis of studies that assessed thigmotaxis in the open field test. Systematic searches were conducted of 3 databases in October 2020, March and August 2022. Study design characteristics and experimental data were extracted and analysed using a random-effects meta-analysis. We also assessed the correlation between thigmotaxis and stimulus-evoked limb withdrawal. This review included the meta-analysis of 165 studies We report thigmotaxis was increased in injury and disease models associated with persistent pain and this increase was attenuated by analgesic drug treatments in both rat and mouse experiments. Its usefulness, however, may be limited in certain injury and disease models because our analysis suggested that thigmotaxis may be associated with the locomotor function. We also conducted subgroup analyses and meta-regression, but our findings on sources of heterogeneity are inconclusive because analyses were limited by insufficient available data. It was difficult to assess internal validity because reporting of methodological quality measures was poor, therefore, the studies have an unclear risk of bias. The correlation between time in the centre (type of a thigmotactic metric) and types of stimulus-evoked limb withdrawal was inconsistent. Therefore, stimulus-evoked and ethologically relevant behavioural paradigms should be viewed as two separate entities as they are conceptually and methodologically different from each other.

Developments in Understanding Diffuse Noxious Inhibitory Controls: Pharmacological Evidence from Pre-Clinical Research.

Bulbospinal pathways regulate nociceptive processing, and inhibitory modulation of nociception can be achieved via the activity of diffuse noxious inhibitory controls (DNIC), a unique descending pathway activated upon application of a conditioning stimulus (CS). Numerous studies have investigated the effects of varied pharmacological systems on the expression status of a) DNIC (as measured in anaesthetised animals) and b) the descending control of nociception (DCN), a surrogate measure of DNIC-like effects in conscious animals. However, the complexity of the underlying circuitry that governs initiation of a top-down inhibitory response in reaction to a CS, coupled with the methodological limitations associated with using pharmacological tools for its study, has often obscured the exact role(s) of a given drug. In this literature review, we discuss the pharmacological manipulation interrogation strategies that have hitherto been used to examine the functionality of DNIC and DCN. Discreet administration of a substance in the spinal cord or brain is considered in the context of action on one of four hypothetical systems that underlie the functionality of DNIC/DCN, where interpreting the outcome is often complicated by overlapping qualities. Systemic pharmacological modulation of DNIC/DCN is also discussed despite the fact that the precise location of drug action(s) cannot be pinpointed. Chiefly, modulation of the noradrenergic, serotonergic and opioidergic transmission systems impacts DNIC/DCN in a manner that relates to drug class, route of administration and health/disease state implicated. The advent of increasingly sophisticated interrogation tools will expedite our full understanding of the circuitries that modulate naturally occurring pain-inhibiting pathways.

Manejo de fractura de platillo tibial medial utilizando placas rim anteromedial y posteromedial / Management of Medial Tibial Plateau Fracture using Antero- and Posteromedial Rim Plates

INTRODUCCION En los últimos años, se ha descrito el uso de placas horizontales para la fijación de fracturas que comprometen el reborde articular de los platillos tibiales, lo que se conoce como placa rim. La mayoría de las publicaciones al respecto describen su uso en columnas posteriores y posterolaterales de los platillos tibiales, y a la fecha hay escasos reportes del uso de este tipo de placa en la columna anteromedial y ninguno para la posteromedial. El objetivo de este artículo es presentar dos casos clínicos de fracturas conminutas del platillo tibial medial mostrando su tratamiento con el uso de placas rim. CASOS CLINICOS El primer caso presentaba compromiso anteromedial y posteromedial, y el segundo, compromiso posteromedial. En ambos casos, se logró la reducción mediante un abordaje posteromedial y su fijación con placa bloqueada de 2,7 mm como placa rim. En cada caso, se detalló la estrategia de reducción y el manejo postoperatorio. RESULTADOS Ambos pacientes consiguieron la consolidación ósea entre las semanas 14 y 18 tras la osteosíntesis definitiva, sin presentar pérdidas de reducción. Ambos lograron rango de movilidad articular completo (0°­125°), y retornaron a sus trabajos a los 4 y 6 meses respectivamente. CONCLUSIONES Estas placas ofrecen una buena opción de tratamiento para fracturas articulares conminutas del borde del platillo tibial, tanto en la columna anteromedial como en la posteromedial. A pesar de la ausencia de grandes series de pacientes con uso de placas rim mediales, el resultado de los casos presentados aquí nos permite plantear su utilidad al momento de enfrentarnos a fracturas del reborde articular

INTRODUCTION In recent years, the use of horizontal plates has been described to achieve fixation of fractures that compromise the articular ridge of the tibial plateau; these plates are known as "rim plates." Most publications report their use in the posterior and posterolateral columns of the tibial plateau, and to date there are few reports of its use for the fixation of the anteromedial column and none for the posteromedial column. The objective of the present article is to report two clinical cases of comminuted fractures of the medial tibial plateau, showing their treatment with the use of medial rim plates. CLINICAL CASES The first case presented with an anteromedial and posteromedial tibial plateau fracture, and the second, a posteromedial fracture. In both cases, reduction was achieved through a posteromedial approach, and the fixation was performed with a 2.7-mm locked rim plate. The reduction strategy and postoperative management were detailed in each case. RESULTS Both patients achieved bone consolidation during the 14th and 18th weeks after the definitive osteosynthesis, without presenting loss of reduction. Both patients achieved full range of joint motion (0°­125°) and returned to work after four and six months respectively. CONCLUSION These plates offer a good treatment option for comminuted fractures of the rim of the tibial plateau, for both the anteromedial and posteromedial columns. Despite the absence of large series of patients with the use of medial rim plates, the results of the two cases herein presented enables us to propose it as a useful tool when dealing with fractures of the medial rim of the tibial plateau

INTRODUCTION In recent years, the use of horizontal plates has been described to achieve fixation of fractures that compromise the articular ridge of the tibial plateau; these plates are known as "rim plates." Most publications report their use in the posterior and posterolateral columns of the tibial plateau, and to date there are few reports of its use for the fixation of the anteromedial column and none for the posteromedial column. The objective of the present article is to report two clinical cases of comminuted fractures of the medial tibial plateau, showing their treatment with the use of medial rim plates. CLINICAL CASES The first case presented with an anteromedial and posteromedial tibial plateau fracture, and the second, a posteromedial fracture. In both cases, reduction was achieved through a posteromedial approach, and the fixation was performed with a 2.7-mm locked rim plate. The reduction strategy and postoperative management were detailed in each case. RESULTS Both patients achieved bone consolidation during the 14th and 18th weeks after the definitive osteosynthesis, without presenting loss of reduction. Both patients achieved full range of joint motion (0°­125°) and returned to work after four and six months respectively. CONCLUSION These plates offer a good treatment option for comminuted fractures of the rim of the tibial plateau, for both the anteromedial and posteromedial columns. Despite the absence of large series of patients with the use of medial rim plates, the results of the two cases herein presented enables us to propose it as a useful tool when dealing with fractures of the medial rim of the tibial plateau