RESUMO
Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.
Assuntos
Neurônios GABAérgicos , Interneurônios , Ketamina , Parvalbuminas , Córtex Pré-Frontal , Sinapses , Animais , Ketamina/farmacologia , Ketamina/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Parvalbuminas/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Masculino , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Camundongos , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/metabolismo , Camundongos Endogâmicos C57BL , Antagonistas de Aminoácidos Excitatórios/farmacologiaRESUMO
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can be effectively controlled by rapid and accurate identification of SARS-CoV-2-infected cases through large-scale screening. Hypercube pooling polymerase chain reaction (PCR) is frequently used as a pooling technique because of its high speed and efficiency. We attempted to implement the hypercube pooling strategy and found it had a large quantization effect. This raised two questions: is hypercube pooling with edge = 3 actually the optimal strategy? If not, what is the best edge and dimension? We used a C++ program to calculate the expected number of PCR tests per patient for different values of prevalence, edge, and dimension. The results showed that every edge had a best performance range. Then, using C++ again, we created a program to calculate the optimal edge and dimension required for pooling samples when entering prevalence into our program. Our program will be provided as freeware in the hope that it can help governments fight the SARS-CoV-2 pandemic.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Teste para COVID-19 , COVID-19/diagnóstico , Pandemias , Reação em Cadeia da PolimeraseRESUMO
Distal radius orientation is important in evaluating Colles' fracture. In most cases, the wrist was protected by a bandage, splint, or cast. Therefore, it was difficult for the radiology technician to take perfect anteroposterior and lateral view radiographs. In this study, we build a mathematical model and calculate the pronation angle needed to produce dorsal tilt, which is a volar tilt in a perfect lateral view radiograph. The formulas are all incorporated into Excel to facilitate usage.
RESUMO
Synaptic pruning during adolescence is important for appropriate neurodevelopment and synaptic plasticity. Aberrant synaptic pruning may underlie a variety of brain disorders such as schizophrenia, autism and anxiety. Dopamine D2 receptor (Drd2) is associated with several neuropsychiatric diseases and is the target of some antipsychotic drugs. Here we generate self-reporting Drd2 heterozygous (SR-Drd2+/-) rats to simultaneously visualize Drd2-positive neurons and downregulate Drd2 expression. Time course studies on the developing anterior cingulate cortex (ACC) from control and SR-Drd2+/- rats reveal important roles of Drd2 in regulating synaptic pruning rather than synapse formation. Drd2 also regulates LTD, a form of synaptic plasticity which includes some similar cellular/biochemical processes as synaptic pruning. We further demonstrate that Drd2 regulates synaptic pruning via cell-autonomous mechanisms involving activation of mTOR signaling. Deficits of Drd2-mediated synaptic pruning in the ACC during adolescence lead to hyper-glutamatergic function and anxiety-like behaviors in adulthood. Taken together, our results demonstrate important roles of Drd2 in cortical synaptic pruning.
Assuntos
Giro do Cíngulo/fisiologia , Plasticidade Neuronal/fisiologia , Receptores de Dopamina D2/fisiologia , Transdução de Sinais/fisiologia , Animais , Animais Geneticamente Modificados , Espinhas Dendríticas/genética , Espinhas Dendríticas/fisiologia , Técnicas de Inativação de Genes , Giro do Cíngulo/citologia , Giro do Cíngulo/metabolismo , Heterozigoto , Potenciais Pós-Sinápticos Inibidores/genética , Potenciais Pós-Sinápticos Inibidores/fisiologia , Mutação , Plasticidade Neuronal/genética , Neurônios/citologia , Neurônios/metabolismo , Neurônios/fisiologia , Técnicas de Patch-Clamp/métodos , Ratos Sprague-Dawley , Receptores de Dopamina D2/genética , Transdução de Sinais/genética , Sinapses/genética , Sinapses/fisiologia , Fatores de TempoRESUMO
BACKGROUND/PURPOSE: Quadriceps-sparing minimally invasive total knee arthroplasty (TKA) has been proposed to limit surgical dissection without compromising surgical outcome. We conducted a prospective and randomized study to compare the outcomes of patients who underwent quadriceps-sparing TKA with the outcomes of those who underwent standard medial parapatellar TKA, after a 2-year follow-up period. METHODS: Eighty primary TKA procedures that were to be performed in 60 osteoarthritis patients were randomly assigned to either a quadriceps-sparing (40 knees) or a standard medial parapatellar (40 knees) group. All surgeries were designed to set the prosthesis with a femoral component alignment of 7° valgus and a tibial component alignment that was perpendicular to the tibial shaft. Surgical time and tourniquet time were recorded. Outcome variables included knee function, as defined by a hospital for special surgery knee score; quadriceps muscle strength, which was measured by an isokinetic dynamometer; pain, as indicated on a visual analog scale; prosthetic position, which was measured on plain radiograph; and range of motion. RESULTS: Patients who underwent the 38 quadriceps-sparing and 37 standard TKA procedures completed the 2-year follow-up period without any infection or revision. The mean surgical time and tourniquet time were significantly longer in the quadriceps-sparing group. The mean peak quadriceps muscle strength, hamstring muscle strength, normalized muscle balance (hamstring/quadriceps ratio), pain score, function score, and range of motion were comparable in both groups at 2 months and 2 years. In the quadriceps-sparing group, both the femoral and the tibial components were significantly more varus-deviated from the expected position. CONCLUSIONS: Patients undergoing quadriceps-sparing and standard medial parapatellar TKA had comparable outcomes for quadriceps muscle strength, hamstring-quadriceps balance, and knee function; however, the quadriceps-sparing TKA was more time consuming surgically and resulted in a less accurate prosthesis position.
Assuntos
Artroplastia do Joelho/métodos , Músculo Quadríceps/cirurgia , Idoso , Artroplastia do Joelho/efeitos adversos , Feminino , Seguimentos , Humanos , Articulação do Joelho/fisiologia , Masculino , Pessoa de Meia-Idade , Força Muscular , Duração da Cirurgia , Tratamentos com Preservação do Órgão , Dor Pós-Operatória/etiologia , Músculo Quadríceps/fisiologia , Amplitude de Movimento ArticularRESUMO
BACKGROUND: Our study was designed to (1) investigate the risk factors associated with cervical or trochanteric hip fractures; and (2) identify the risk factors for increased mortality in the elderly population sustaining hip fractures, after adjusting the miscellaneous baseline prefracture conditions. METHODS: Two hundred seventeen elder patients with first-time, low-trauma hip fractures were enrolled. The follow-up time ranged from 35 months to 56 months. Potential risk factors for hip fracture types included (1) the 77 items on the self-reported questionnaire; (2) the body height, weight, and body mass index; (3) tests of coordination, handgrip strength, and peak expiratory flow rate; and (4) the bone mineral density variables. GTFN ratio was defined as the bone mineral density ratio between the greater trochanter and the femoral neck. Multivariate logistic regression and Cox regression models were used for analysis. The population attributable risk proportion of death to each significant factor was estimated. RESULTS: Risk factors for trochanteric fractures include a GTFN ratio ≤0.81, being male, and an age >80 years. Risk factors for higher mortality after hip fracture included trochanteric fracture, body mass index ≤20 (kg/m), poor self-assessed health status, peak expiratory flow rate ≤215 (L/min), being male, illiteracy, and coordination abnormality, in the declining order of population attributable risk proportion. Trochanteric fractures had a significantly higher cumulative mortality at 36 months, 48 months, and 60 months than cervical fractures. CONCLUSIONS: The novel GTFN ratio was associated with hip fracture sites. Clinically, cervical and trochanteric fractures represent different disease entities because of the difference in their mortality rates.
Assuntos
Fixação Interna de Fraturas/métodos , Fraturas do Quadril/epidemiologia , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Densidade Óssea , Feminino , Seguimentos , Fraturas do Quadril/etiologia , Fraturas do Quadril/cirurgia , Humanos , Incidência , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Taxa de Sobrevida/tendências , Taiwan/epidemiologiaRESUMO
BACKGROUND: Taping has been used to treat patellofemoral pain syndrome for more than 20 years, but its effectiveness is still controversial. PURPOSE: This study was undertaken to investigate the effect and predictors of effectiveness of taping in the treatment of patellofemoral pain syndrome. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 118 consecutive patients with patellofemoral pain syndrome were recruited; 100 of them completed this study. Patient sex, age, body mass index, Q angle, lateral patellar displacement, and lateral patellofemoral angle were recorded/measured. One therapist applied adhesive tape to each patient by the McConnell method. Patients scored their pain level on a 100-mm visual analog scale during stepping down from an 8-in platform, before and after taping. The change of score was evaluated by paired t test. Patients with a visual analog scale score decrease of 20 mm or more after taping were considered responsive, and the others were considered nonresponsive. The influences of the aforementioned factors, plus pretaping visual analog scale score, on the effectiveness of taping were analyzed by multivariate logistic regression. RESULTS: The overall mean visual analog scale score decreased significantly after taping (from 49.0 to 29.3 mm; P < .001). There were 66 patients in the responsive group and 34 in nonresponsive group. Among the factors, body mass index, lateral patellofemoral angle, and Q angle were significant predictors of effectiveness. The responsive group had significantly smaller mean lateral patellofemoral angle, larger mean Q angle, and larger mean pretaping visual analog scale score than the nonresponsive group. CONCLUSION: Taping was an effective treatment for patellofemoral pain syndrome, but was less effective in patients with higher body mass index, larger lateral patellofemoral angle, and smaller Q angle.
Assuntos
Bandagens/normas , Síndrome da Dor Patelofemoral/terapia , Adulto , Estudos de Coortes , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
UNLABELLED: In this prospective study, we compared outcomes after repair of humeral nonunions when morsellized fresh-frozen allograft or autograft was used to augment repair by intramedullary nailing. Sixty-five patients with humeral shaft nonunions of greater than 6 months' duration and gross instability at the nonunion site were included and treated by locked nailing, interfragmentary wiring, and bone grafting. Graft type was determined by patient preference. Outcomes assessed included union rate and functional recovery of the arm. Secondary end points included operative blood loss, operation time, hospital stay, time to fracture healing, and complications. Twenty-eight patients with autografts and 36 with allografts were followed up more than 2 years. The baseline conditions of the two groups were similar. The autograft group had greater blood loss and longer operative time than the allograft group. The autograft group also had a longer hospital stay. The healing rate, time to healing, and functional scores did not differ between these two groups. In the autograft group, 43% reported pain and limited mobility as a result of the donor site. We concluded that when used in association with locked nailing for humeral nonunions, allografts can achieve treatment results similar to autografts but without donor site complications. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
Assuntos
Transplante Ósseo/métodos , Fios Ortopédicos , Fixação Interna de Fraturas/métodos , Fraturas não Consolidadas/cirurgia , Fraturas do Úmero/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Pinos Ortopédicos , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/instrumentação , Consolidação da Fratura , Fraturas não Consolidadas/fisiopatologia , Humanos , Fraturas do Úmero/fisiopatologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
Our study was conducted to compare radiographic alignments and functional outcomes with 2 approaches to minimal-incision total knee arthroplasty (TKA): the minimal-incision medial parapatellar (MP) approach and the quadriceps-sparing (QS) approach with side-cutting instruments. Sixty patients (80 knees) with primary osteoarthritis were randomly assigned to receive MP or QS TKA. Postoperative alignment of the femoral component was significantly less valgus, and postoperative alignment of the tibial component was significantly more varus with the QS approach than with the MP approach. One tibial outlier and 3 femoral outliers were observed with QS TKA. The overall postoperative hip-knee-ankle axis was more varus, and surgical time was longer with QS TKA. Short-term isokinetic peak muscle torque, postoperative pain, and functional outcomes did not differ between the approaches.
Assuntos
Artroplastia do Joelho/métodos , Articulação do Joelho/fisiologia , Articulação do Joelho/cirurgia , Prótese do Joelho , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Músculo Quadríceps/fisiologia , Músculo Quadríceps/cirurgia , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/instrumentação , Fenômenos Biomecânicos , Mau Alinhamento Ósseo/diagnóstico por imagem , Mau Alinhamento Ósseo/prevenção & controle , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Força Muscular/fisiologia , Osteoartrite do Joelho/cirurgia , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos , Músculo Quadríceps/diagnóstico por imagem , Radiografia , Método Simples-Cego , Torque , Resultado do TratamentoRESUMO
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty. METHODS: This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA) morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS) pain scores, active range of motion (ROM), total opioid use and postoperative nausea/vomiting were analyzed. RESULTS: Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 +/- 1.68 vs. 3.43 +/- 1.50, p = 0.03) and 72 hrs (1.78 +/- 1.66 vs. 3.17 +/- 2.01, p = 0.02) after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8 degrees +/- 17.3 degrees vs. 25.8 degrees +/- 11.5 degrees , p = 0.01 (day 1); 60.7 degrees +/- 18.1 degrees vs. 45.0 degrees +/- 17.3 degrees , p = 0.004 (day 2); 77.7 degrees +/- 15.1 degrees vs. 64.3 degrees +/- 16.9 degrees , p = 0.004 (day 3)]. Opioid requirements decreased about 40% (p = 0.03) in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57). There were no differences in blood loss (intra- and postoperative) between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions. CONCLUSION: Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid consumption, and active ROM in the first three days after total knee arthroplasty, without increasing the risks of bleeding. TRIAL REGISTRATION: Clinicaltrials.gov NCT00598234.