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Fetal alcohol spectrum disorder (FASD) encompasses a range of cognitive and behavioral deficits, with aberrances in the function of cerebral cortical pyramidal neurons implicated in its pathology. However, the mechanisms underlying these aberrances, including whether they persist well beyond ethanol exposure in utero, remain to be explored. We addressed these issues by employing a mouse model of FASD in which pregnant mice were exposed to binge-type ethanol from embryonic day 13.5 through 16.5. In both male and female offspring (postnatal day 28–32), whole-cell patch clamp recording of layer V/VI somatosensory cortex pyramidal neurons revealed increases in the frequency of excitatory and inhibitory postsynaptic currents. Furthermore, expressing channelrhodopsin in either GABAergic interneurons (Nkx2.1Cre-Ai32) or glutamatergic pyramidal neurons (Emx1IRES Cre-Ai32) revealed a shift in optically evoked paired-pulse ratio. These findings are consistent with an excitatory-inhibitory imbalance with prenatal ethanol exposure due to diminished inhibitory but enhanced excitatory synaptic strength. Prenatal ethanol exposure also altered the density and morphology of spines along the apical dendrites of pyramidal neurons. Thus, while both presynaptic and postsynaptic mechanisms are affected following prenatal exposure to ethanol, there is a prominent presynaptic component that contributes to altered inhibitory and excitatory synaptic transmission in the somatosensory cortex.

Objectives Platelet-rich fibrin matrix (PRFM) has been proved to enhance tenocyte proliferation but has mixed results when used during rotator cuff repair. The optimal PRFM preparation protocol should be determined before clinical application. To screen the best PRFM to each individual’s tenocytes effectively, small-diameter culture wells should be used to increase variables. The gelling effect of PRFM will occur when small-diameter culture wells are used. A co-culture device should be designed to avoid this effect. Methods Tenocytes harvested during rotator cuff repair and blood from a healthy volunteer were used. Tenocytes were seeded in 96-, 24-, 12-, and six-well plates and co-culture devices. Appropriate volumes of PRFM, according to the surface area of each culture well, were treated with tenocytes for seven days. The co-culture device was designed to avoid the gelling effect that occurred in the small-diameter culture well. Cell proliferation was analyzed by water soluble tetrazolium-1 (WST-1) bioassay. Results The relative quantification (condition/control) of WST-1 assay on day seven revealed a significant decrease in tenocyte proliferation in small-diameter culture wells (96 and 24 wells) due to the gelling effect. PRFM in large-diameter culture wells (12 and six wells) and co-culture systems induced a significant increase in tenocyte proliferation compared with the control group. The gelling effect of PRFM was avoided by the co-culture device. Conclusion When PRFM and tenocytes are cultured in small-diameter culture wells, the gelling effect will occur and make screening of personalized best-fit PRFM difficult. This effect can be avoided with the co-culture device. Cite this article: C-H. Chiu, P. Chen, W-L. Yeh, A. C-Y. Chen, Y-S. Chan, K-Y. Hsu, K-F. Lei. The gelling effect of platelet-rich fibrin matrix when exposed to human tenocytes from the rotator cuff in small-diameter culture wells and the design of a co-culture device to overcome this phenomenon. Bone Joint Res 2019;8:216–223. DOI: 10.1302/2046-3758.85.BJR-2018-0258.R1.

Exposure of the fetus to alcohol (ethanol) via maternal consumption during pregnancy can result in fetal alcohol spectrum disorders (FASD), hallmarked by long-term physical, behavioral, and intellectual abnormalities. In our preclinical mouse model of FASD, prenatal ethanol exposure disrupts tangential migration of corticopetal GABAergic interneurons (GINs) in the embryonic medial prefrontal cortex (mPFC). We postulated that ethanol perturbed the normal pattern of tangential migration via enhancing GABAAreceptor-mediated membrane depolarization that prevails during embryonic development in GABAergic cortical interneurons. However, beyond this, our understanding of the underlying mechanisms is incomplete. Here, we tested the hypothesis that the ethanol-enhanced depolarization triggers downstream an increase in high-voltage-activated nifedipine-sensitive L-type calcium channel (LTCC) activity and provide evidence implicating calcium dynamics in the signaling scheme underlying the migration of embryonic GINs and its aberrance. Tangentially migrating Nkx2.1+GINs expressed immunoreactivity to Cav1.2, the canonical neuronal isoform of the L-type calcium channel. Prenatal ethanol exposure did not alter its protein expression profile in the embryonic mPFC. However, exposing ethanol concomitantly with the LTCC blocker nifedipine prevented the ethanol-induced aberrant migration bothin vitroandin vivo. In addition, whole-cell patch clamp recording of LTCCs in GINs migrating in embryonic mPFC slices revealed that acutely applied ethanol potentiated LTCC activity in migrating GINs. Based on evidence reported in the present study, we conclude that calcium is an important intracellular intermediary downstream of GABAAreceptor-mediated depolarization in the mechanistic scheme of an ethanol-induced aberrant tangential migration of embryonic GABAergic cortical interneurons.

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.

Identifying cost-effective decisions that can take into account of medical cost and health outcome is an important issue under very limited resources. Analyzing medical costs has been challenged owing to skewness of cost distributions, heterogeneity across samples and censoring. When censoring is due to administrative reasons, the total cost might be related to the survival time since longer survivals are likely to be censored and the corresponding total cost will be censored as well. This paper uses the general linear model for the longitudinal data to model the repeated medical cost data and the weighted estimating equation is used to find more accurate estimates for the parameter. Furthermore, the asymptotic properties for the proposed model are discussed. Simulations are used to evaluate the performance of estimators under various scenarios. Finally, the proposed model is implemented on the data extracted from National Health Insurance database for patients with the colorectal cancer.

Aim To determine the relationship between knee pain following anterior cruciate ligament (ACL) graft placement with morphological graft findings and dynamic contrast enhancement as assessed at MRI. Material and methods Following institutional review board approval, 37 consecutive patients with double-bundle ACL reconstruction were enrolled. Thirteen patients had pain and 24 were asymptomatic. Imaging was performed using a 1.5 T MRI machine an average of 7.6 months after surgery. Graft-related (increase signal intensity, abnormal orientation, discontinuity, cystic degeneration, anterior translation of lateral tibia, arthrofibrosis), and non-graft related causes of knee pain (meniscal tear, cartilage injury, loose bodies, and synovitis) were evaluated. During dynamic contrast enhancement analysis, peak enhancement (ePeak) was calculated by placing a region of interest at the osteoligamentous interface of each bundle. Student's t -test was used for continuous variables analysis and chi-square or Fisher's exact test was used for categorical variables analysis. Results There was no difference between symptomatic and asymptomatic patients regarding morphological graft-related or non-graft-related causes of knee pain. For dynamic contrast enhancement analysis, symptomatic patients had significantly lower ePeak values than asymptomatic patients in the anteromedial ( p = 0.008) and posterolateral ( p = 0.001) bundles or when using the higher ePeak value in either bundle ( p = 0.003). Conclusion Morphological ACL graft findings as assessed at MRI could not be used to distinguish between symptomatic and asymptomatic patients. However, lower ePeak values had a significant association with knee pain. This may indicate poor neovascularization of the graft, potentially leading to graft failure.

We analyzed our clinical results in 48 patients (40 men) treated during 1990-1993 with free vascularized bone-graft reconstruction for bone defects, the follow-up being an average 6 (5-8) years. The bone defects were located in the femur (10), tibia (32), humerus (2), and forearm (4). We performed 41 fibula transfers, 4 iliac transfers, and 3 rib transfers in these patients. 3 patients required early revision surgery due to venous thrombosis. The average time needed for radiographic bone union was 4.2 months. Bone transfers to the lower extremity showed significantly more hypertrophy than those in the upper extremity. The functional outcome was good in 43 patients.

Open fracture in the lower extremity often involves composite bone and soft-tissue defects. For patients with extensive segmental bone defects, vascularized fibular transfers can be utilized and are generally accepted as one of the best options for reconstruction of intercalary defects. In some cases, either bilateral tibias and fibulas are fractured or the contralateral fibula is traumatically damaged or absent, precluding free fibular transfer. If an osteocutaneous fibular flap cannot be used to manage such a defect, a composite serratus anterior and rib flap may be considered. Nine composite serratus anterior and rib flaps, with or without latissimus dorsi transfers, were performed in eight patients between August of 1993 and March of 1994. One patient sustained a left knee disarticulation and underwent reconstruction for a right tibial defect. He failed to achieve lower extremity function within 2 years and was considered a failure. One flap failed, and the patient underwent a below-knee amputation. The remaining six patients received seven composite flaps for tibial and calcaneal defects and could ambulate without assistance. Based on this review, we conclude that the composite serratus anterior and rib flap with optional latissimus dorsi muscle can be used for (1) bilateral tibial fibular fractures, (2) contralateral lower limb amputation with fillet of the amputated leg if the leg is present for harvest, (3) contralateral middle-third fracture of the fibula, (4) patients in whom iliac bone is not suitable because of either a bone defect greater than 10 to 12 cm or previous harvest of bone graft, and (5) extensive composite bone and soft-tissue defects.

Motor imagery base brain-computer interface (BCI) is an appropriate solution for stroke patient to rehabilitate and communicate with external world. For such applications speculating whether the subjects are doing motor imagery is our primary mission. So the problem turns into how to precisely classify the two tasks, motor imagery and idle state, by using the subjects' electroencephalographic (EEG) signals. Feature extraction is a factor that significantly affects the classification result. Based on the concept of Continuous Wavelet Transform, we proposed a wavelet-liked feature extraction method for motor imagery discrimination. And to compensate the problem that the feature varies between subjects, we use the subjects' own EEG signals as the mother wavelet. After determining the feature vector, we choose Bayes linear discriminant analysis (LDA) as our classifier. The BCI competition III dataset IVa is used to evaluate the classification performance. Comparing with variance and fast Fourier transform (FFT) methods in feature extraction, 2.02% and 16.96% improvement in classification accuracy are obtained in this work respectively.

Several 2-carbalkoxy-2-cyclohepten-1-ones were prepared and their Diels–Alder characteristics examined in order to develop a facile general approach to the synthesis of cycloheptane ring-containing polycyclic natural products. Substitution pattern on the seven-membered ring was found to greatly affect the Diels–Alder behavior. In addition, some extraordinary facial stereoselectivity was observed. Keywords: Diels–Alder reaction, 2-carbalkoxy-2-cyclohepten-1-ones, 6,7-fused ring system.

A formal synthesis of longifolene in racemic form is concluded starting from the Diels–Alder reaction of 6,6-di-methylfulvene and maleic anhydride. Key steps are cyclodehydration, conjugate methyla...

Several 2-carbalkoxy-2-cyclohepten-1-ones were prepared and their Diels–Alder characteristics examined in order to develop a facile general approach to the synthesis of cycloheptane ring-containing...

A formal synthesis of longifolene in racemic form is concluded starting from the Diels–Alder reaction of 6,6-di-methylfulvene and maleic anhydride. Key steps are cyclodehydration, conjugate methylation, and ring expansion.

Cajal-Retzius cells are implicated in regulating neuronal migration and lamination during corticogenesis. In rodents, Cajal-Retzius cells are transient, being prevalent in the marginal zone of the embryonic neocortex and declining over the first two postnatal weeks. While studies have examined in postnatal neocortex the properties of GABA(A) receptors in Cajal-Retzius cells, less is known about their disposition at embryonic stages. Here, we combined patch-clamp electrophysiology and single-cell mRNA profiling to probe the expression of GABA(A) receptors in Cajal-Retzius cells. In embryonic neocortical slices, GABA elicited GABA(A) receptor-mediated current responses that were diazepam-insensitive and inhibited by Zn(2+), a pharmacological profile consistent with expression of gamma-less GABA(A) receptor isoforms. Non-Cajal-Retzius cells in the same embryonic slices, on the other hand, were robustly potentiated by diazepam and were insensitive to Zn(2+), typical of gamma-containing GABA(A) receptor isoforms, as were Cajal-Retzius cells in the postnatal neocortex. Single-cell mRNA profiling and immunohistochemistry confirmed expression of GABA(A) receptor gamma subunit transcript and protein, respectively, in individual reelin-expressing cells in the postnatal cortex but not in their embryonic counterparts. We conclude that Cajal-Retzius cells express gamma-less GABA(A) receptors at embryonic stages and switch to expressing gamma-containing GABA(A) receptor isoforms during postnatal neocortical development.

Surgical reduction of PCL avulsion fracture was performed from posterior approach and arthroscopic treatment was not routinely performed. However, associated intraarticular lesions of meniscus, cartilage, of any other pathologies were very common in PCL injuries. If the treatments of associated intraarticular lesions would improve the results was not known. Under this prospective study, we want to know if arthroscope is valuable in PCL avulsion fractures.From January 1995 to December 1997, there were 29 cases of PCL avulsion fractures. They were grouped according to chart numbers. Group I was even number group and group II was odd number group. Arthroscopic examination was performed in even number group, but not in odd number group. Group I had 13 cases and group II had 16 cases. All the PCL avulsion fractures were repaired from posterior approach and fixed with cancellous screws.The range of motion, arthrometric data, and Lysholm score were similar in both group after more than 2 years of follow-up. The residual pain was less in arthroscopic group. Arthroscopic examination showed hemarthrosis in all cases of group I; meniscal lesion in 7 cases (54%), osteochondral or chondral lesions in 3 cases (23%), hard medial plica in 3 cases (23%), patellofemoral lesion in 1 case (7.7%), ACL tear in 1 case (7.7%), popliteal lesion in 2 cases (15.4%), lateral opening greater than 1 cm in 5 cases (38.5%). Though the functional results were similar in both groups, the arthroscopic findings in PCL avulsion fracture were negative in only 2 cases.Arthroscopic examination in PCL avulsion fracture can provide valuable information.

Although the adult Monteggia fracture is a well-known injury, the combination of a Monteggia fracture and an ipsilateral distal radius fracture is extremely rare. It is important for the treating physician to recognize that this injury involves not only the bone elements but also their articulations. The distortion of the integrity of both the elbow and the wrist results in the potential for functional compromise, if inadequately treated. The case report presented here describes a 21-year-old woman with this complex injury resulting from a fall. The injury included a Monteggia type II fracture and an ipsilateral distal radius intra-articular fracture in the left forearm. An excellent result was obtained by surgical intervention in both the radial and ulnar bones. The factors we believe contributed to the excellent result were early diagnosis, anatomic reduction, stable fixation, and early physical exercise. The mechanism of injury giving rise to this rare combination of fractures is discussed, as well as a review of the literature.

Compartment syndromes occurring in the forearm and leg are not infrequent. However, reports of compartment syndrome of the upper arm are conspicuously rare. Inferior dislocation of the shoulder combined with compartment syndrome has rarely been reported in the literature. We report our experience with a patient with inferior dislocation of the glenohumeral joint combined with compartment syndrome of the upper arm. A 29-year-old man had traumatic inferior dislocation of the glenohumeral joint combined with severe swelling of the shoulder and upper arm. After close reduction, the shoulder and upper arm were still tensely swollen. Compartment pressure of the upper arm was measured using a digital manometer (Quick Pressure Monitor 295-1, Stryker) and remained very high, thus, fasciotomy was performed. After debridement and skin graft, the arm healed without sequelae. When a patient has a fracture dislocation of the shoulder joint associated with a swollen arm, compartment syndrome of the upper arm should be included as a differential diagnosis. Detecting the compartment pressure can confirm the diagnosis of compartment syndrome objectively.

Open fracture in the lower extremity often involves composite bone and soft-tissue defects. For patients with extensive segmental bone defects, vascularized fibular transfers can be utilized and are generally accepted as one of the best options for reconstruction of intercalary defects. In some cases, either bilateral tibias and fibulas are fractured or the contralateral fibula is traumatically damaged or absent, precluding free fibular transfer. If an osteocutaneous fibular flap cannot be used to manage such a defect, a composite serratus anterior and rib flap may be considered. Nine composite serratus anterior and rib flaps, with or without latissimus dorsi transfers, were performed in eight patients between August of 1993 and March of 1994. One patient sustained a left knee disarticulation and underwent reconstruction for a right tibial defect. He failed to achieve lower extremity function within 2 years and was considered a failure. One flap failed, and the patient underwent a below-knee amputation. The remaining six patients received seven composite flaps for tibial and calcaneal defects and could ambulate without assistance. Based on this review, we conclude that the composite serratus anterior and rib flap with optional latissimus dorsi muscle can be used for (1) bilateral tibial fibular fractures, (2) contralateral lower limb amputation with fillet of the amputated leg if the leg is present for harvest, (3) contralateral middle-third fracture of the fibula, (4) patients in whom iliac bone is not suitable because of either a bone defect greater than 10 to 12 cm or previous harvest of bone graft, and (5) extensive composite bone and soft-tissue defects.

One case of gouty patient with aseptic loosening of cementless total hip arthroplasty was reported. Mechanical and biological factors may both play some roles in this ollsening hip. From both cup and stem, no direct evidence of loosening was found from pathologic aspect. Further study may need to define relationship between gout and loosening of total hip arthroplasty.

After preliminary field screening at Tifton, Ga., 23 groundnut germplasm lines were evaluated at Isabella, Puerto Rico against Puccinia arachidis and 22 of them at Patancheru, Andhra Pradesh, India and Guangzhou, Guangdong, China against the rust and Cercosporidium personatum (Mycosphaerella berkeleyi) in 1976-81. At all 3 locations 9 were resistant to P. arachidis; 6 of these (PI1259747, PI350680, PI381622, PI405132, PI215696 and PI341879) were resistant also to M. berkeleyi and could prove useful in breeding for multiple resistance. The last 2 entries are newly reported as resistant to both pathogens.