Long-term clinical course and outcomes in patients with lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder with various clinical manifestations. Despite the recognition of several prognostic factors, the long-term clinical course and prognosis of patients with LAM in the era of sirolimus therapy are not established. METHODS: The clinical data of 104 patients with LAM were retrospectively analyzed. Death or lung transplantation was defined as the primary outcome. Disease progression (DP) was defined as a 10% absolute decline in forced expiratory volume in one second (FEV1). RESULTS: The mean age of all patients was 40.3 years. Over a median follow-up period of 7.1 years, of all patients, 6.7% died and 1.9% underwent lung transplantation, while of 92 patients with serial lung function data, 35.9% experienced DP. The 5-year and 10-year overall survival rates were 93.0% and 90.9%, respectively. The multivariable Cox analysis revealed that older age (hazard ratio [HR]: 1.136, P = 0.025), lower FEV1 (HR: 0.956, P = 0.026) or diffusing capacity for carbon monoxide (HR: 0.914, P = 0.003), and shorter distance during the 6-min walk test (HR: 0.993, P = 0.020) were independent prognostic factors for mortality. A propensity score-matched comparative analysis performed between patients who received sirolimus therapy and those who did not, found no differences in survival, DP, complications, and lung function decline rate. CONCLUSIONS: Over a follow-up period of approximately 7 years, one-tenth of all patients experienced death, while one-third experienced DP. Older age, lower lung function, and reduced exercise capacity were associated with a poor prognosis in patients with LAM.

Identification of quinone analogues as potential inhibitors of picornavirus 3C protease in vitro.

Picornaviruses are non-enveloped viruses that represent a large family of positive-sense single-stranded RNA viruses including a number of causative agents of many human and animal diseases such as coxsackievirus B3 (CVB3) and rhinoviruses (HRV). In this study, we performed a high-throughput screening of a compound library composed of ∼6000 small molecules in search of potential picornavirus 3C protease (3Cpro) inhibitors. As results, we identified quinone analogues that effectively inhibited both CVB3 3Cpro and HRV 3Cpro with IC50 values in low micromolar range. Together with predicted binding modes of these compounds to the active site of the viral protease, it is implied that structural features of these non-peptidic inhibitors may act as useful scaffold for further anti-picornavirus drug design and development.

Anodal Transcranial Direct Current Stimulation Provokes Neuroplasticity in Repetitive Mild Traumatic Brain Injury in Rats.

Repetitive mild traumatic brain injury (rmTBI) provokes behavioral and cognitive changes. But the study about electrophysiologic findings and managements of rmTBI is limited. In this study, we investigate the effects of anodal transcranial direct current stimulation (tDCS) on rmTBI. Thirty-one Sprague Dawley rats were divided into the following groups: sham, rmTBI, and rmTBI treated by tDCS. Animals received closed head mTBI three consecutive times a day. Anodal tDCS was applied to the left motor cortex. We evaluated the motor-evoked potential (MEP) and the somatosensory-evoked potential (SEP). T2-weighted magnetic resonance imaging was performed 12 days after rmTBI. After rmTBI, the latency of MEP was prolonged and the amplitude in the right hind limb was reduced in the rmTBI group. The latency of SEP was delayed and the amplitude was decreased after rmTBI in the rmTBI group. In the tDCS group, the amplitude in both hind limbs was increased after tDCS in comparison with the values before rmTBI. Anodal tDCS after rmTBI seems to be a useful tool for promoting transient motor recovery through increasing the synchronicity of cortical firing, and it induces early recovery of consciousness. It can contribute to management of concussion in humans if further study is performed.

Termination of the ligamentum venosum and the topographic relationship between the left portal vein, left hepatic artery, and ligamentum venosum in the fissures for the ligamentum teres and ligamentum venosum.

PURPOSE: The aim of this study was to clarify the location of termination of the ligamentum venosum (LV) and topographic relationships between the left portal vein (LPV), left hepatic artery (LHA), and LV in the fissures for ligamentum teres and LV. METHODS: Anatomical examination was performed on 50 livers from embalmed Korean adult cadavers. RESULTS: The LV originated from a point between the transverse and umbilical portions of LPV (Tr-Um point) in all specimens, and terminated in the common trunk of the middle hepatic vein and left hepatic vein (LHV) (61%) or in the LHV (39%). In the fissures for ligamentum teres and LV, the courses of the LHA relative to the LV and the LPV varied, such that four main patterns could be discerned. In type I (48%), the LHA crossed the inferior surface of Tr-Um point and passed just left of the origin of LV. In type II (20%), the LHA crossed the inferior surface of umbilical portion of LPV. In type III (10%), the LHA crossed the inferior surface of Tr-Um point to pass just left of origin of LV, with one branch of the right hepatic artery crossing the inferior surface of umbilical portion of LPV. In type IV (12%), no arterial branches ran on the inferior surfaces of transverse and umbilical portions of LPV. CONCLUSION: These details may play a role as external landmarks for facilitating preestimation of intrahepatic structures during various surgical procedures involving the liver.

New insights into the origin of the lumbrical muscles of the foot: tendinous slip of the flexor hallucis longus muscle.

PURPOSE: The aim of this study was to clarify the origins of the lumbricals of the foot toward a better understanding of its precise action in the gait. METHODS: The lumbricals in the foot were investigated in 66 specimens of embalmed Korean adult cadavers. RESULTS: The first lumbrical arose as two muscle bellies from both the tendon of the FDL and the tendinous slip of the FHL in 83.3 %, and as one muscle belly from the tendon of the FDL or the tendinous slip of the FHL in 16.7 %. These two muscle bellies subsequently merged to form the muscle belly of the first lumbrical. The second lumbrical arose from the tendinous slips of the FHL for the second and third toes as well as the tendon of the FDL in all specimens. The third lumbrical arose from the tendinous slips of the FHL for the third and fourth toes in 69.7 %, and the fourth lumbrical arose from the tendinous slip of the FHL for the fourth toe in 18.2 %. Some deep muscle fibers of the fourth lumbrical arose from the tendinous slip of the FHL for the second toe in 4.5 %, for the third toe in 28.8 %, and for the fourth toe in 15.2 %. CONCLUSIONS: The results of this study constitute new anatomical knowledge regarding the origin of the lumbricals, and provide insight into their specific role in production of gait. These findings will be useful for various types of surgery, biomechanics research, and rehabilitation programs.

Blending of the lateral deep slip of the platysma muscle into the buccinator muscle.

PURPOSE: The aim of this study was to clarify the prevalence of blending of the lateral deep slip of the platysma into the buccinator, and the morphologic and spatial relationships thereof. METHODS: The lateral deep slip of the platysma was investigated in 42 specimens of embalmed adult Korean cadavers. RESULTS: The lateral deep slip of the platysma was observed in 17 of the 42 specimens (40.5 %). When present, it divided from the deep portion (16 specimens, 38.1 %) or the lateral portion (1 specimen, 2.4 %) of the platysma pars modiolaris. The lateral deep slip passed deep to the facial artery, where it blended into the inferior part of the buccinator. The blending site was located inferolateral to the modiolus. After blending into the buccinator, the fibers of the lateral deep slip coursed longitudinally with the inferior fibers of the buccinator. CONCLUSION: The present description of the topography of the lateral deep slip of the platysma and its relationship with surrounding structures could improve the understanding of the detailed movements of the lower face and the related EMG activities, with the data also being useful when performing facial surgery.

An anatomic study of the medial fibers of depressor anguli oris muscle passing deep to the depressor labii inferioris muscle.

The trajectory of the medial fibers of depressor anguli oris muscle that pass deep to the depressor labii inferioris muscle (dDAO) and the anatomic relationship have not yet been examined. The aim of this study was to clarify the arrangement of the dDAO and its relationships with the surrounding structures. The dDAOs were investigated in 40 hemifaces from Korean cadavers. The dDAOs were observed in 18 of the 40 specimens (45%). The anatomic relationships of the dDAO were classified into the following 4 categories according to their connection with the incisivus labii inferioris muscle (ILI): (1) connected to the ILI and attached to the inferior border of the mandible lateral to the mentalis muscle (14 specimens, 35%), (2) connected to the ILI and intermingled with the lateral lower fibers of the mentalis muscle (2 specimens, 5%), (3) connected to the ILI but neither attached to the mandible nor intermingled with the mentalis muscle (1 specimen, 2.5%), and (4) not connected to the ILI but intermingled with the mentalis muscle (1 specimen, 2.5%). Therefore, in 17 specimens, the dDAOs were connected to the ILI (42.5%), in 14 specimens, they were attached to the inferior border of the mandible (35%), and, in 3 specimens, they were intermingled with the mentalis muscle (7.5%). The new anatomic data regarding the dDAO will contribute toward the understanding of movements of the mouth and lower face, which will be helpful when designing effective botulinum toxin type A therapies and performing various types of facial surgery.

Long-lasting forms of plasticity through patterned ultrasound-induced brainwave entrainment.

Achieving long-lasting neuronal modulation with low-intensity, low-frequency ultrasound is challenging. Here, we devised theta burst ultrasound stimulation (TBUS) with gamma bursts for brain entrainment and modulation of neuronal plasticity in the mouse motor cortex. We demonstrate that two types of TBUS, intermittent and continuous TBUS, induce bidirectional long-term potentiation or depression-like plasticity, respectively, as evidenced by changes in motor-evoked potentials. These effects depended on molecular pathways associated with long-term plasticity, including N-methyl-d-aspartate receptor and brain-derived neurotrophic factor/tropomyosin receptor kinase B activation, as well as de novo protein synthesis. Notably, bestrophin-1 and transient receptor potential ankyrin 1 play important roles in these enduring effects. Moreover, pretraining TBUS enhances the acquisition of previously unidentified motor skills. Our study unveils a promising protocol for ultrasound neuromodulation, enabling noninvasive and sustained modulation of brain function.

Morphology of the mentalis muscle and its relationship with the orbicularis oris and incisivus labii inferioris muscles.

The mentalis muscle (MT) is the only elevator of the lower lip and the chin, and it provides the major vertical support for the lower lip. However, there are few reports on the relationship between the MT and its surrounding muscles. The aim of this study was to clarify the morphology of the MT, especially in relation to the orbicularis oris muscle and the incisivus labii inferioris muscle (ILI), thereby providing data to understand the function of the MT in relation to the surrounding muscles. The MT was examined in 40 specimens of embalmed adult Korean cadavers. The medial fibers of both MTs descended anteromedially and crossed together, forming a dome-shaped chin prominence in all specimens. The lateral fibers of the MT descended inferomedially in 38 specimens (95%) and inferolaterally in 2 specimens (5%). The upper fibers of the MT were short and ran horizontally, whereas the lower fibers were long and descended inferomedially or vertically. The upper fibers of the MT were intermingled with the inferior margin of the orbicularis oris muscle in all specimens. The originating muscle fibers of the ILI were intermingled with the upper lateral MT in all specimens. Some of the ILI fibers extended inferomedially to the middle or lower portion of the MT in 22 specimens (55%). The results of this study constitute new anatomical knowledge regarding the MT and will be useful to surgeons performing various surgical procedures of the chin area.

Chin-tuck assistant system (CAS)-A novel method using auditory feedback for postural maintenance in a chin-tuck maneuver: A randomized trial.

INTRODUCTION: Chin-tuck are effective in patients with dysphagia, where aspiration can occur due to pharyngeal swallowing delays. This study aims to verify whether Chin-tuck Assistant System Maneuver (CAS-M) supplemented with Chin-Tuck Maneuver (CTM) is effective for learning and maintaining correct chin-tuck postures. In addition, we investigated the possibility of using CAS-M as a customized rehabilitation treatment program for patients with poor cognitive ability, attention issues, and general swallowing disorders. INTERVENTION: To demonstrate the effectiveness of CAS, we recruited 52 healthy adults and assigned them to 2 groups. The CTM group was trained to maintain the correct chin-tuck posture using the general Chin-Tuck Maneuver, while the CAS-M group was trained using CAS. Four evaluations were conducted using CAS to investigate the degree of postural maintenance of chin-tuck before and after intervention. RESULTS: The CAS-M group showed a statistically significant difference in TIME, BEEP, and change (P < .05), but the CTM group showed no statistically significant differences (P < .05). YZ evaluation showed no statistically significant differences in both groups. CONCLUSION: After examining the effects of CAS-M using CAS on healthy adults, we confirmed this to be a more effective method for correct chin-tuck posture than conventional CTM.

Destination of the C4 component of the prefixed brachial plexus.

This study was carried out to elucidate the destination of the C4 ventral ramus that forms the prefixed brachial plexus. A total of 43 sides of Korean adults (male, 22; female, 18; unknown: 3 and right, 23; left, 20) were investigated. The various C4 destinations and their frequencies were as follows: suprascapular nerve, 97.7% (42/43); musculocutaneous nerve, 79.1% (34/43); the axillary nerve, 48.8% (21/43); and the nerve to subclavius, 16.2% (7/43). The mean quantity of nerve fibers destined to the suprascapular, musculocutaneous, and axillary nerves and the nerve to subclavius was 441.8 ± 316.5 (Mean ± S.D.), 298.2 ± 209.8, 245.8 ± 239.0, and 66.4 ± 17.2, respectively. The mean nerve fibers number of C4 contributing to the brachial plexus was 983.6 ± 618.0 (range: 100-1729). The main component that contributes to the terminal nerves (suprascapular, musculocutaneous, axillary nerves, and nerve to subclavius) is C5. These results may be useful to surgeons and clinicians dealing with terminal nerves of the brachial plexus, especially the suprascapular, musculocutaneous, and axillary nerves.

Long-term clinical course and outcome in patients with primary Sjögren syndrome-associated interstitial lung disease.

Interstitial lung disease (ILD) is the most common lung manifestation in patients with Sjögren syndrome (SJS) and is associated with poor outcomes. This study aimed to investigate the long-term clinical course and prognostic factors in patients with SJS-ILD. Clinical data and high-resolution computed tomography (HRCT) images of 62 patients with primary SJS-ILD were retrospectively analyzed (biopsy-proven cases, n = 16). The mean patient age was 59.8 years; 83.9% of the patients were females, and 38.7% showed a usual interstitial pneumonia (UIP) pattern on HRCT. The median follow-up period was 61.5 months. During follow-up, 15 patients (24.2%) died, 7 (11.3%) experienced acute exacerbation (AE), and 27 (43.5%) progressed. The 1-, 3- and 5-year survival rates were 93.5%, 85.8%, and 81.1%, respectively. Age (hazard ratio [HR]: 1.158, P = 0.003), C-reactive protein (CRP) level (HR: 1.212, P = 0.045), FVC (HR: 0.902, P = 0.005), and a UIP pattern on HRCT (HR: 4.580, P = 0.029) were significant prognostic factors in multivariable Cox analysis. In conclusion, death, AE, and ILD progression occurred in 25%, 10%, and 50% of the patients with SJS-ILD, respectively. Older age, higher CRP level, lower FVC, and a UIP pattern on HRCT indicated poor prognosis.

Clinical characteristics and outcomes of Korean patients with sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unknown cause involving multiple organs. Its clinical presentation and prognosis vary among races. We identified the clinical characteristics and outcomes of Korean patients with sarcoidosis. Clinical data of 367 Korean patients with biopsy-proven sarcoidosis diagnosed in 2001-2017 were retrospectively analyzed. Treatment responses included improvement, stability, or progression based on changes in pulmonary sarcoidosis on chest images. The mean age was 47.4 years, and 67.3% of patients were women. The median follow-up period was 80 months. The highest prevalence was observed in individuals aged 50-59 years (30-39 years in men, 50-59 years in women), and the number of diagnoses showed an increasing trend. Lung involvement was the most common (93.5%), followed by the skin, eyes, and extrathoracic lymph nodes. Among patients with lung involvement and a follow-up period of ≥ 3 months, 66.8%, 31.0%, and 2.2% showed improvement, stability, and progression, respectively. Eleven patients (2.9%) died, and the 5-year survival rate was 99%. The number of diagnosed cases showed an increasing trend, and the mean age at diagnosis was increased compared with that in previous reports. Organ involvement was similar to that of Westerners, although the prognosis appeared better.

An abnormal muscle in the superficial region of the popliteal fossa.

An abnormal muscle was observed in the superficial region of the popliteal fossa during a dissection procedure conducted for medical students. This abnormal muscle originated from the biceps femoris tendon and inserted into the medial head of the gastrocnemius muscle. The innervating nerve branched from the lateral sural cutaneous nerve. The distributing artery arose from a branch of the sural artery. This abnormal muscle mostly comprised one sheet of muscle mass (not tendon type) and ran transversely.

Dissolution of biomacromolecules in organic solvents by nano-complexing with poly(ethylene glycol).

Various biomacromolecules (BMs) such as proteins, DNA, and carbohydrates are extremely difficult to be dissolved in a single organic solvent phase for sustained release or targeted delivery formulation. In this study, three different BMs could be solubilized in selected organic solvents by forming poly(ethylene glycol) (PEG)-assisted nano-complexes while maintaining their structural integrity. Dynamic light scattering (DLS) and atomic force microscopy (AFM) analysis revealed that proteins, DNA, and carbohydrate polymers could be nano-complexed with PEG in various organic solvents. The diameter of nano-complexes decreased roughly from approximately 600 nm to approximately 100 nm with increasing weight ratio of PEG/BM. The present solubilization technique could be potentially applied for sustained release formulations of various therapeutic biological drugs.

The spinal root origins and clinical implications of the lower subscapular nerve.

The purpose of this study was to define the spinal root origins of the lower subscapular nerve and the amounts of participating nerve fibers from each spinal root and to discuss the clinical implications. Using a method of separating the nerve fascicles that traces the particular nerve fibers at the intrafascicular level, the spinal root origins of the lower subscapular nerve appeared as two types. The first type comprised 76.9% and was composed of the C5, C6, and C7 roots; the second type comprised 23.1% and was composed of the C6 and C7 roots. The number of nerve fibers was 357.2 +/- 139.7 (mean +/- SD) derived from C5, 1070.4 +/- 390.6 from C6, and 500.0 +/- 285.4 from C7. The nerve fascicles comprising the lower subscapular nerve traveled within the partially common fascicles composed of the axillary nerve. Therefore, injury of the lower subscapular nerve may be accompanied by a lesion of the axillary nerve, which generally consists of C5 and C6 roots composing the posterior cord of the brachial plexus.

Removal of arsenic from groundwater by micellar-enhanced ultrafiltration (MEUF).

The removal characteristics of arsenate using micellar-enhanced ultrafiltration (MEUF) were investigated. Among four different cationic surfactants used, hexadecylpyridinium chloride (CPC) showed the highest removal efficiency of arsenic (96%), and the removal efficiency with hexadecyltrimethylammonium bromide (CTAB) was 94%. But the removal efficiency with benzalkonium chloride (BC) was the lowest (57%) due to higher critical micelle concentration (CMC) of BC than those of other surfactants. Over 80% of arsenic was removed with octadecylamine acetate (ODA). On the effect of solution pH on the arsenic removal, since the valance of arsenate decreases from trivalent to monovalent as pH decreases, the removal was reduced at lower pH. The presence of 0.45mM of nitrate and 0.01mM of phosphate reduced the removal efficiency by 5-8%. This decrease was because of the competition between the arsenate, nitrate and phosphate for the binding sites of the surfactant micelle. Similar decrease in the removal of arsenate was observed with CPC, CTAB and ODA in the presence of these anions. In cross-flow filtration, the removal efficiency of arsenic was similar to that in the dead-end system. However, the decline in flux was less than that in dead-end filtration. In order to lower the concentration of the surfactant in the effluent, the effluent was treated with powdered activated carbon (PAC) before discharging to the environment. Over 98% surfactant was removed with 1gl(-1) of PAC. In conclusions, the MEUF is considered as a feasible process using CPC or CTAB to remove the arsenate from groundwater compared with the other solid based adsorbent processes.

Glycosylation of flavonoids with E. coli expressing glycosyltransferase from Xanthomonas campestris.

Glycosyltransferase family 1 (UGT) uses small chemicals including phenolics, antibiotics, and alkaloids as substrates to have an influence in biological activities. A glycosyltransferase (XcGT-2) from Xanthomonas campestris was cloned and consisted of a 1,257 bp open reading frame encoding a 45.5 kDa protein. In order to use this for the modification of phenolic compounds, XcGT-2 was expressed in Escherichia coli as a glutathione S-transferase fusion protein. With the E. coli transformant expressing XcGT-2, biotransformation of flavonoids was carried out. Flavonoids having a double bond between carbons 2 and 3, and hydroxyl groups at both C-3' and C-4', were glycosylated and the glycosylation position was determined to be at the hydroxyl group of C-3', using nuclear magnetic resonance spectroscopy. These results showed that XcGT-2 regiospecifically transferred a glucose molecule to the 3'-hydroxyl group of flavonoids containing both 3' and 4'-hydroxyl groups.

A simple rat model of mild traumatic brain injury: a device to reproduce anatomical and neurological changes of mild traumatic brain injury.

Mild traumatic brain injury typically involves temporary impairment of neurological function. Previous studies used water pressure or rotational injury for designing the device to make a rat a mild traumatic brain injury model. The objective of this study was to make a simple model of causing mild traumatic brain injury in rats. The device consisted of a free-fall impactor that was targeted onto the rat skull. The weight (175 g) was freely dropped 30 cm to rat's skull bregma. We installed a safety device made of acrylic panel. To confirm a mild traumatic brain injury in 36 Sprague-Dawley rats, we performed magnetic resonance imaging (MRI) of the brain within 24 h after injury. We evaluated behavior and chemical changes in rats before and after mild traumatic brain injury. The brain MRI did not show high or low signal intensity in 34 rats. The mobility on grid floor was decreased after mild traumatic brain injury. The absolute number of foot-fault and foot-fault ratio were decreased after mild traumatic brain injury. However, the difference of the ratio was a less than absolute number of foot-fault. These results show that the device is capable of reproducing mild traumatic brain injury in rats. Our device can reduce the potential to cause brain hemorrhage and reflect the mechanism of real mild traumatic brain injury compared with existing methods and behaviors. This model can be useful in exploring physiology and management of mild traumatic brain injury.

Induction of immunogenic cell death of tumors by newly synthesized heterocyclic quinone derivative.

Many cancer types are serious diseases causing mortality, and new therapeutics with improved efficacy and safety are required. Immuno-(cell)-therapy is considered as one of the promising therapeutic strategies for curing intractable cancer. In this study, we tested R2016, a newly developed heterocyclic quinone derivative, for induction of immunogenic tumor cell death and as a possible novel immunochemotherapeutic. We studied the anti-cancer effects of R2016 against LLC, a lung cancer cell line and B16F10, a melanoma cell line. LLC (non-immunogenic) and B16F10 (immunogenic) cells were killed by R2016 in dose-dependent manner. R2016 reduced the viability of both LLC and B16F10 tumor cells by inducing apoptosis and necrosis, while it demonstrated no cytotoxicity against normal splenocytes. Expression of immunogenic death markers on the cell surface of R2016 treated tumor cells including calreticulin (CRT) and heat shock proteins (HSPs) was increased along with the induction of their genes. Increased CRT expression correlated with dendritic cell (DC) uptake of dying tumor cells: the proportion of CRT+CD11c+cells was increased in the R2016-treated group. The gene transcription of Calr3, Hspb1, and Tnfaip6, which are related to immunogenicity induction of dead cells, was up-regulated in the R2016 treated tumor cells. On the other hand, ANGPT1, FGF7, and URGCP gene levels were down-regulated by R2016 treatment. This data suggests that R2016 induced immunogenic tumor cell death, and suggests R2016 as an effective anti-tumor immunochemotherapeutic modality.