Alternating mealtimes during pregnancy and weaning triggers behavioral changes in adult offspring.

In brief: Mealtime changes in pregnant mice revealed impaired neurobehavioral development in mouse offspring. This study is the basis for investigating diseases associated with neurobehavioral development of adult offspring of pregnant shift-working women. Abstract: Most organisms on Earth have a biological clock, and their physiological processes are regulated by a 1-day cycle. In modern society, several factors can disturb these biological clocks in humans; in particular, individuals working in shifts are exposed to stark environmental changes that interfere with their biological clock. They have a high risk of various diseases. However, there are scarce experimental approaches to address the reproductive and health consequences of shift work in the offspring of exposed individuals. In this study, considering the fact that shift workers usually have their meals during their adjusted working time, we aimed to examine the effects of a 12-h shift with usual mealtime as a plausible night work model on the neurobehavioral development of adult mouse offspring. In these offspring, early exposure to this mealtime shift differentially affected circadian rhythmic variables and total locomotor activity depending on the timing and duration of restrictive feeding. Moreover, neurobehavioral alterations such as declined short-term memory and depressive-like behavior were observed in adulthood. These results have implications for the health concerns of shift-working women and their children.

Mealtime shift delays conception in mice.

The physiological processes of organisms in this rotating planet can adjust according to the time of day via built-in circadian clocks. However, more people are having different shift works, which can increase the risk of pathological conditions including altered reproductive function. Thus, circadian rhythm disturbance has become prevalent in the modern society. Specifically, epidemiological evidence has shown that shift-working women are at high risk of spontaneous abortions, irregular menstrual cycles, and low-birth-weight babies. The current study aimed to investigate the effects of circadian rhythm disturbances on the reproductive function of mice caused by dietary time shift, which is common among night-shift workers. According to the schedule of restricted feeding, the mice were classified into the free feeding, daytime feeding, and night feeding groups. The fertility indices of each group were then evaluated. Activity monitoring was performed to determine whether pregnancy delay might be attributed to mealtime shift. Moreover, the estrous cycle of female mice and the reproductive phenotype of male mice were investigated. Results showed that a 12-h mealtime shift significantly delayed successful conception, which could be attributed to a disrupted estrous cycle, in adult female mice.

Moderate aerobic exercise training ameliorates impairment of mitochondrial function and dynamics in skeletal muscle of high-fat diet-induced obese mice.

The purpose of this study is to determine whether moderate aerobic exercise training improves high-fat diet-induced alterations in mitochondrial function and structure in the skeletal muscle. Male 4-week-old C57BL/6 mice were randomly divided into four groups: control (CON), control plus exercise (CON + EX), high-fat diet (HFD), and high-fat diet plus exercise (HFD + EX). After obesity was induced by 20 weeks of 60% HFD, treadmill exercise training was performed at 13-16 m/min, 40-50 min/day, and 6 days/week for 12 weeks. Mitochondrial structure, function, and dynamics, and mitophagy were analyzed in the skeletal muscle fibers from the red gastrocnemius. Exercise training increased mitochondrial number and area and reduced high-fat diet-induced obesity and hyperglycemia. In addition, exercise training attenuated mitochondrial dysfunction in the permeabilized myofibers, indicating that HFD-induced decrease of mitochondrial O2 respiration and Ca2+ retention capacity and increase of mitochondrial H2 O2 emission were attenuated in the HFD + EX group compared to the HFD group. Exercise also ameliorated HFD-induced imbalance of mitochondrial fusion and fission, demonstrating that HFD-induced decrease in fusion protein levels was elevated, and increase in fission protein levels was reduced in the HFD + EX groups compared with the HFD group. Moreover, dysregulation of mitophagy induced by HFD was mitigated in the HFD + EX group, indicating a decrease in PINK1 protein level. Our findings demonstrated that moderate aerobic exercise training mitigated obesity-induced insulin resistance by improving mitochondrial function, and reversed obesity-induced mitochondrial structural damage by improving mitochondrial dynamics and mitophagy, suggesting that moderate aerobic exercise training may play a therapeutic role in protecting the skeletal muscle against mitochondrial impairments and insulin resistance induced by obesity.

Attenuation effect of polydeoxyribonucleotide on inflammatory cytokines and apoptotic factors induced by particulate matter (PM10) damage in human bronchial cells.

Particulate matter (PM) of 10-µm-sized fine dust in the air penetrates the respiratory tract and contributes to the increasing incidence of various lung diseases, but its definite mechanism is not known. Recently, polydeoxyribonucleotide (PDRN) has been shown to have anti-inflammatory and regenerative effects in various tissues. However, the bronchial-related mechanism is not well-understood. Hence, this experiment is intended to demonstrate the beneficial effect of PDRN administration on PM10-induced injury in human bronchial-derived NCI-H358 cells. To confirm the protective effect of PDRN, PM10 was applied after PDRN pretreatment to confirm changes in NCI-H358 cells. Experiments were conducted to measure cell survival, cytotoxicity, inflammation, and apoptotic factor changes. WST-8 assay was used to confirm cell viability, and lactate dehydrogenase assay was used to obtain cytotoxicity. In addition, changes in inflammatory cytokines and apoptotic factors were confirmed by enzyme-linked immunosorbent assay and Western blot. Decreased cell viability and increased cytotoxicity, inflammatory cytokines, and apoptotic factors were observed after exposure to PM10. However, pretreatment with PDRN enhanced cell viability and reduced cytotoxicity. In addition, the expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1ß, and cell death factors such as Apaf-1, cyt c, caspase-3, caspase-9, Bid, and Bax/Bcl-2 ratio were decreased by PDRN administration in PM10-exposed NCI-H358 cells. PDRN, an A2AR agonist, affects cAMP activation and regulation of phosphorylation of PKA and CREB. In addition, treatment with A2AR antagonist 3,7-dimethyl-1-propargylxanthine significantly blocked PDRN's effect. These anti-cytotoxicity, anti-inflammation, and anti-apoptosis effects of PDRN can be attributed to the adenosine A2AR enhancing effect on PM10-exposed bronchial cells.

Effects of aging and exercise training on mitochondrial function and apoptosis in the rat heart.

Aging is associated with vulnerability to cardiovascular diseases, and mitochondrial dysfunction plays a critical role in cardiovascular disease pathogenesis. Exercise training is associated with benefits against chronic cardiac diseases. The purpose of this study was to determine the effects of aging and treadmill exercise training on mitochondrial function and apoptosis in the rat heart. Fischer 344 rats were divided into young sedentary (YS; n = 10, 4 months), young exercise (YE; n = 10, 4 months), old sedentary (OS; n = 10, 20 months), and old exercise (OE; n = 10, 20 months) groups. Exercise training groups ran on a treadmill at 15 m/min (young) or 10 m/min (old), 45 min/day, 5 days/week for 8 weeks. Morphological parameters, mitochondrial function, mitochondrial dynamics, mitophagy, and mitochondria-mediated apoptosis were analyzed in cardiac muscle. Mitochondrial O2 respiratory capacity and Ca2+ retention capacity gradually decreased, and mitochondrial H2O2 emitting potential significantly increased with aging. Exercise training attenuated aging-induced mitochondrial H2O2 emitting potential and mitochondrial O2 respiratory capacity, while protecting Ca2+ retention in the old groups. Aging triggered imbalanced mitochondrial dynamics and excess mitophagy, while exercise training ameliorated the aging-induced imbalance in mitochondrial dynamics and excess mitophagy. Aging induced increase in Bax and cleaved caspase-3 protein levels, while decreasing Bcl-2 levels. Exercise training protected against the elevation of apoptotic signaling markers by decreasing Bax and cleaved caspase-3 and increasing Bcl-2 protein levels, while decreasing the Bax/Bcl-2 ratio and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive myonuclei. These data demonstrate that regular exercise training prevents aging-induced impairment of mitochondrial function and mitochondria-mediated apoptosis in cardiac muscles.

Simultaneous Clamping and Cutting Force Measurements with Built-In Sensors.

The intensity of the clamping force during milling operations is very important, because an excessive clamping force can distort the workpiece, while inadequate clamping causes slippage of the workpiece. Since the overall clamping force can be affected by the cutting forces throughout machining, it is necessary to monitor the change of clamping and the cutting forces during the process. This paper proposes a hybrid system in the form of a vise with built-in strain gauges and in-house-developed piezoelectric sensors for simultaneous measurement of clamping and cutting forces. Lead zirconate titanate (PZT) sensors are fabricated and embedded in a layered jaw to measure the dynamic forces of the machine tool. A cross-shaped groove within the jaw is designed to embed strain gauges, which predominantly measure the static clamping forces. Sensor fusion technology combining the signals of the strain gauges and PZT piezoelectric sensors is used to investigate the interactions between cutting forces and clamping forces. The results show average errors of 11%, 17%, and 6% for milling forces in X, Y, and Z directions, respectively; and 19% error for clamping forces, confirming the capability of the setup to monitor the forces in milling.

Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice.

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 µL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

A Randomized Controlled Trial Investigating the Effects of Equine Simulator Riding on Low Back Pain, Morphological Changes, and Trunk Musculature in Elderly Women.

Background and objectives: Studies on the effects of an equine riding simulator (ERS) program on back pain, spinal alignment, and isokinetic moments in subjects with chronic low back pain (CLBP) remain limited. The purpose of this study was to analyze changes in elderly women with CLBP who participate in an ERS program. Materials and Methods: The 80 participants were all women aged 61-84 years who were randomly assigned to either the control group (CON) or ERS group (ERSG). ERS exercise was performed for a duration of 12 weeks (three times each week). The degree of pain was measured using the Oswestry Disability Index and the visual analog scale. Body composition and spinal alignment were measured using bioelectrical impedance and raster stereography. The isokinetic moments of trunk extensor and flexor were measured before and after the training period. Results: The ERSG showed a significant decrease in back pain compared to the CON. There was a significant decrease in levels of fat in the ERSG, although no differences were shown in terms of muscle mass. However, there was an increased basal metabolic rate (BMR) in the ERSG. Spinal alignment in the ERSG significantly improved. The peak torques of the trunk extensor in the ERSG were also significantly increased. Conclusion: It can be inferred that the ERS exercise can decrease fat and improve the trunk extensor strength through increased BMR, leading to better spinal alignment and reducing back pain in elderly women with CLBP.

The Effects of Kaempferol-Inhibited Autophagy on Osteoclast Formation.

Kaempferol, a flavonoid compound, is derived from the rhizome of Kaempferia galanga L., which is used in traditional medicine in Asia. Autophagy has pleiotropic functions that are involved in cell growth, survival, nutrient supply under starvation, defense against pathogens, and antigen presentation. There are many studies dealing with the inhibitory effects of natural flavonoids in bone resorption. However, no studies have explained the relationship between the autophagic and inhibitory processes of osteoclastogenesis by natural flavonoids. The present study was undertaken to investigate the inhibitory effects of osteoclastogenesis through the autophagy inhibition process stimulated by kaempferol in murin macrophage (RAW 264.7) cells. The cytotoxic effect of Kaempferol was investigated by MTT assay. The osteoclast differentiation and autophagic process were confirmed via tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, western blot, and real-time PCR. Kaempferol controlled the expression of autophagy-related factors and in particular, it strongly inhibited the expression of p62/SQSTM1. In the western blot and real time-PCR analysis, when autophagy was suppressed with the application of 3-Methyladenine (3-MA) only, osteoclast and apoptosis related factors were not significantly affected. However, we found that after cells were treated with kaempferol, these factors inhibited autophagy and activated apoptosis. Therefore, we presume that kaempferol-inhibited autophagy activated apoptosis by degradation of p62/SQSTM1. Further study of the p62/SQSTM1 gene as a target in the autophagy mechanism, may help to delineate the potential role of kaempferol in the treatment of bone metabolism disorders.

Polydeoxyribonucleotide Ameliorates Lipopolysaccharide-Induced Lung Injury by Inhibiting Apoptotic Cell Death in Rats.

Lung injury is characterized by diffuse lung inflammation, alveolar-capillary destruction, and alveolar flooding, resulting in respiratory failure. Polydexyribonucleotide (PDRN) has an anti-inflammatory effect, decreasing inflammatory cytokines, and suppressing apoptosis. Thus, we investigated its efficacy in the treatment of lung injury, which was induced in rats using lipopolysaccharide (LPS). Rats were randomly divided into three groups according to sacrifice time, and each group split into control, lung injury-induced, and lung injury-induced + PDRN-treated groups. Rats were sacrificed 24 h and 72 h after PDRN administration, according to each group. Lung injury was induced by intratracheal instillation of LPS (5 mg/kg) in 0.2 mL saline. Rats in PDRN-treated groups received a single intraperitoneal injection of 0.3 mL distilled water including PDRN (8 mg/kg), 1 h after lung injury induction. Percentages of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive, cleaved caspase-3-, -8-, and -9-positive cells, the ratio of Bcl-2-associated X protein (Bax) to B-cell lymphoma 2 (Bcl-2), and expressions of inflammatory cytokines (tumor necrosis factor-α, interleukin-6) were decreased by PDRN treatment in the LPS-induced lung injury rats. Therefore, treatment with PDRN reduced lung injury score. This anti-apoptotic effect of PDRN can be ascribed to the enhancing effect of PDRN on adenosine A2A receptor expression. Based on these results, PDRN might be considered as a new therapeutic agent for the treatment of lung injury.

Effect of Chaenomeles sinensis Extract on Choline Acetyltransferase Activity and Trimethyltin-Induced Learning and Memory Impairment in Mice.

The aim of this study was to search for a novel choline acetyltransferase (ChAT) activator from plants traditionally grown in Korea. An ethanol extract from Chaenomeles sinensis Koehne showed the highest ChAT-activating effect in vitro in an assay that used human neuroblastoma cells and [(14)C]acetyl-CoA. The active compound was speculated to be stearic acid methyl ester (SAME). In an in vivo experiment, C. sinensis extract and SAME improved trimethyltin (TMT)-induced deficits in learning and memory in mice as assessed by a Y-maze behavioral test and a passive avoidance test. The C. sinensis extract might attenuate the TMT-induced brain disorder. This study suggests that SAME from C. sinensis might be useful in the treatment of Alzheimer's disease.

Effect of backpack position on foot weight distribution of school-aged children.

[Purpose] In the present study, we aimed to determine the effects of backpack position on foot weight distribution of standing school-aged children. [Subjects] Thirty school-aged children volunteered to participate in this study. [Methods] The subjects randomly performed four types of carrying a backpack: no backpack (condition-1), carrying a backpack at C7 (condition-2), carrying a backpack at 10 cm below C7 (condition-3), and carrying a backpack at 20 cm below C7 (condition-4). [Results] Statistically significant differences were noted in the anterior and posterior pressure values, and in the anterior-to-posterior ratio, among the four conditions (p < 0.05). Post-hoc analysis indicated that the pressure value of condition-4 was significantly lower in the anterior foot region and higher in the posterior foot region than in condition-2 and condition-3. In addition, the anterior-to-posterior ratio was lower in condition-4 than in condition-2 and condition-3. [Conclusion] These findings suggest that carrying a backpack in a higher position, with fastening of the shoulder strap, may be more favorable for normalizing the foot weight distribution.

Oral mucosa stem cells alleviates spinal cord injury-induced neurogenic bladder symptoms in rats.

BACKGROUND: Spinal cord injury (SCI) deteriorates various physical functions, in particular, bladder problems occur as a result of damage to the spinal cord. Stem cell therapy for SCI has been focused as the new strategy to treat the injuries and to restore the lost functions. The oral mucosa cells are considered as the stem cells-like progenitor cells. In the present study, we investigated the effects of oral mucosa stem cells on the SCI-induced neurogenic bladder in relation with apoptotic neuronal cell death and cell proliferation. RESULTS: The contraction pressure and the contraction time in the urinary bladder were increased after induction of SCI, in contrast, transplantation of the oral mucosa stem cells decreased the contraction pressure and the contraction time in the SCI-induced rats. Induction of SCI initiated apoptosis in the spinal cord tissues, whereas treatment with the oral mucosa stem cells suppressed the SCI-induced apoptosis. Disrupted spinal cord by SCI was improved by transplantation of the oral mucosa stem cells, and new tissues were increased around the damaged tissues. In addition, transplantation of the oral mucosa stem cells suppressed SCI-induced neuronal activation in the voiding centers. CONCLUSIONS: Transplantation of oral mucosa stem cells ameliorates the SCI-induced neurogenic bladder symptoms by inhibiting apoptosis and by enhancing cell proliferation. As the results, SCI-induced neuronal activation in the neuronal voiding centers was suppressed, showing the normalization of voiding function.

Comparison of Spatiotemporal Gait Parameters between Children with Normal Development and Children with Diplegic Cerebral Palsy.

[Purpose] The purpose of this study was to determine the differences in spatiotemporal gait parameters between children with spastic diplegic CP and children with normal development (ND). [Subjects and Methods] Sixteen children (eight children with spastic diplegic CP and eight ND children) were recruited for participation as volunteers in this study. The children with CP had a Gross Motor Function Classification (GMFC) System level of between I and II. [Results] Walking velocity, cadence, stride length, and step width of children with CP with a GMFC of between I and II were a level of 60%, 77%, 73%, and 160%, respectively, of those of ND children. The percentages of right and left double-limb support were 188% and 179% higher, respectively, and the proportion of single limb support was shorter by 83% and 82%. [Conclusion] Our results provide objective evidence of distinct differences in spatiotemporal gait parameters between children with spastic diplegic CP with a GMFC level I or II and ND children and would be helpful to persons involved in the care of these children.

Comparison of children with joint angles in spastic diplegia with those of normal children.

[Purpose] The purpose of this study was to compare joint angles between normal children and those with spastic diplegia using three-dimensional gait analysis. [Subjects and Methods] The study subjects were eight patients with spastic diplegia and eight normal children. Three-dimensional gait analysis was used for the survey. The measured gait variables were the joints of the lower extremity in the sagittal plane, frontal plane, and transverse planes and the maximum and minimum angles of their stance phase and swing phases. [Results] In the sagittal plane, the maximum angles of both the right and left pelvis and hip joint in the stance phase and swing phases were significantly greater for children with spastic diplegia than for normal children. In the stance phase of the right side of the hip joint, the maximum angles of the hip in the swing phase and the knee joint's minimum angles in the stance phase differed significantly. In the transverse plane, there were a significant differences on the left side of the pelvis in the maximum angles in the swing and stance phases. There were also significant differences on the right side pelvis, in the maximum and minimum angles in the stance phase and minimum angles in the swing phase. [Conclusion] Children with spastic diplegia employ a different gait strategy and pattern from normal children.

Effects of Transcranial Direct Current Stimulation on Clinical Features of Dizziness and Cortical Activation in a Patient with Vestibular Migraine.

BACKGROUND: Vestibular migraine (VM) is common migraine that occurs in patients with dizziness. Vestibular rehabilitation for managing VM generally remains unclear. Recently, it has been reported that transcranial direct current stimulation (tDCS) has positive effects in alleviating dizziness. This study investigated the effects of tDCS on dizziness and cortical activation in a patient with VM. METHODS: We recruited a male patient aged 31 years with no dizziness. The patient watched a video to induce dizziness using a virtual reality device. The study applied the intervention using tDCS for 4 weeks and measured 4 assessments: functional near-infrared spectroscopy (fNIRS), quantitative electroencephalography (qEEG), dizziness handicap inventory, and visual vertigo analog scale. RESULTS: We showed the activation in the middle temporal gyrus and inferior temporal gyrus (ITG) of the left hemisphere and in the superior temporal gyrus and ITG of the right hemisphere in the pre-intervention. After the intervention, the activation of these areas decreased. In the results of qEEG, excessive activation of C3, P3, and T5 in the left hemisphere and C4 in the right hemisphere before intervention disappeared after the intervention. CONCLUSIONS: This study indicated that tDCS-based intervention could be considered a viable approach to treating patients with vestibular dysfunction and dizziness caused by VM.

Pirfenidone improves voiding function by suppressing bladder fibrosis in underactive bladder rats.

Underactive bladder (UAB), characterized by a complex set of symptoms with few treatment options, can significantly reduce the quality of life of affected people. UAB is characterized by hyperplasia and fibrosis of the bladder wall as well as decreased bladder compliance. Pirfenidone is a powerful anti-fibrotic agent that inhibits the progression of fibrosis in people with idiopathic pulmonary fibrosis. In the current study, we evaluated the efficacy of pirfenidone in the treatment of bladder fibrosis in a UAB rat model. UAB was induced by crushing damage to nerve bundles in the major pelvic ganglion. Forty-two days after surgery, 1 mL distilled water containing pirfenidone (100, 300, or 500 mg/kg) was orally administered once every 2 days for a total of 10 times for 20 days to the rats in the pirfenidone-treated groups. Crushing damage to the nerve bundles caused voiding dysfunction, resulting in increased bladder weight and the level of fibrous related factors in the bladder, leading to UAB symptoms. Pirfenidone treatment improved urinary function, increased bladder weight and suppressed the expression of fibrosis factors. The results of this experiment suggest that pirfenidone can be used to ameliorate difficult-to-treat urological conditions such as bladder fibrosis. Therefore, pirfenidone treatment can be considered an option to improve voiding function in patient with incurable UAB.

An animal study to compare the degree of the suppressive effects on the afferent pathways of micturition between tamsulosin and sildenafil.

BACKGROUND: Tamsulosin, an α1-adrenoceptor antagonist, and sildenafil, a phosphodiesterase (PDE) inhibitor, are reported to improve lower urinary tract symptoms including overactive bladder (OAB). This study is aimed at investing the effects of tamsulosin and sildenafil and comparing the degree of the suppressive effects on the afferent pathways of micturition between them using an animal model of OAB, the spontaneously hypertensive rat (SHR). RESULTS: The cystometric parameters, the basal pressure and duration of bladder contraction, were significantly increased in the SHR group as compared with the Wistar-Kyoto (WKY) group. The intercontraction interval also significantly decreased in the SHR group. In the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group, however, the basal pressure and duration were significantly reduced and the intercontraction interval was significantly prolonged. Moreover, the degree of the expression of c-Fos and NGF was significantly higher in the SHR group as compared with the WKY group. But it was significantly reduced in the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group. Furthermore, tamsulosin had a higher degree of effect as compared with sildenafil. CONCLUSIONS: In conclusion, α1-adrenergic receptor antagonists and PDE-5 inhibitors may have an effect in improving the voiding functions through an inhibition of the neuronal activity in the afferent pathways of micturition.

Physiotherapy strategies for functional improvement in a child with complicated hereditary spastic paraplegia: 1-year follow-up of a case report using a changing criterion design.

BACKGROUND: and Purpose: Hereditary spastic paraplegias (HSP) are a group of clinically diverse genetic disorders that share the neurologic symptom of difficulty in walking due to progressive serious muscle weakness and spasticity in the legs. This study describes a physiotherapy program for improving the functional ability of a child diagnosed with complicated HSP and reports the treatment results. METHODS: A 10-year-old boy with complicated HSP received a physiotherapy intervention that included strengthening of the leg muscles and treadmill training for 1 h per session, three to four times a week for 6 weeks. Outcome measures included sit-to-stand, 10-m walk, 1-min walk tests, and gross motor function measures (dimensions D and E). RESULTS: After the intervention, the sit-to-stand, 1-min walk, and 10-m walk test scores improved by 6.75 times, 2.57 m, and 0.05 m/s, respectively. Furthermore, the gross motor function measure dimensions D and E scores improved by 8% (46%-54%) and 5% (22%-27%), respectively. The gains in each parameter were maintained at the 3- and 6-month and 1-year follow-ups. CONCLUSION: These results suggest that structured physiotherapy programs can benefit the functional rehabilitation of children with complicated HSP.

Application of concentrated deep sea water inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice.

BACKGROUND: Mineral water from deep-sea bedrock, formed over thousands of years, is rich in minerals such as Ca, Mg, Na, K, Fe and others. Our present study was to investigate the preventive effects of natural deep-sea water on developing atopic dermatitis (AD). METHODS: We elicited AD by application of DNCB (2,4-dinitro-chlorobezene) in Nc/Nga mouse dorsal skin. Deep Sea water (DSW) was filtered and concentrated by a nanofiltration process and reverse osmosis. We applied concentrated DSW (CDSW) to lesions five times per week for six weeks, followed by evaluation. 1% pimecrolimus ointment was used as positive control. The severity of skin lesions was assessed macroscopically and histologically. Levels of inflammatory mediators and cytokines in the serum were detected by Enzyme-linked immunosorbent assay (ELISA) and the levels of CD4+ and CD8+ spleen lymphocytes were determined by flow cytometry analysis. RESULTS: DNCB-treated mice showed atopic dermatitis-like skin lesions. Treatment of mice with CDSW reduced the severity of symptoms in the skin lesions, including edema, erythema, dryness, itching, and transepidermal water loss (TEWL). Histological analyses demonstrated that epidermal thickness and infiltration of inflammatory cells were decreased after CDSW treatment. Given these interesting observations, we further evaluated the effect of CDSW on immune responses in this AD model. Treatment AD mice with CDSW inhibited up-regulation of IgE, histamine, and pro-inflammatory cytokines in the serum. Also, the CD4+/CD8+ ratio in spleen lymphocyte was down-regulated after treatment with CDSW. Finally, cytokines, especially IL-4 and IL-10 which are important for Th2 cell development, were reduced. CONCLUSIONS: Our data suggests that topical application of CDSW could be useful in preventing the development of atopic dermatitis.