Voluntary running attenuates behavioural signs of low back pain: dimorphic regulation of intervertebral disc inflammation in male and female SPARC-null mice.

OBJECTIVE: To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model. METHODS: Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1ß, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1ß, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR. RESULTS: Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1ß, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males. CONCLUSIONS: Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific.

Impact of COVID-19 on TB epidemiology in South Korea.

SETTING: Five referral hospitals, South Korea.OBJECTIVE: To assess epidemiological changes in TB before and during the COVID-19 pandemic.DESIGN: This was a multicentre cohort study of 3,969 patients diagnosed with TB.RESULTS: We analysed 3,453 patients diagnosed with TB prior to the COVID-19 pandemic (January 2016-February 2020) and 516 during the pandemic (March-November 2020). During the pandemic, the number of patients visits declined by 15% from the previous 4-year average, and the number of patients diagnosed with TB decreased by 17%. Patients diagnosed during the pandemic were older than those diagnosed before the pandemic (mean age, 60.2 vs. 56.6 years, P < 0.001). The proportion of patients to have primary TB at a younger age (births after 1980) among those diagnosed with TB was significantly lower during the pandemic than before (17.8% in 2020 vs. 23.5% in 2016, 24.0% in 2017, 22.5% in 2018, 23.5% in 2019; P = 0.005).CONCLUSIONS: The COVID-19 pandemic resulted in a reduction in the number of visits to respiratory departments, leading to fewer patients being diagnosed with TB. However, our results suggest that universal personal preventive measures help to suppress TB transmission in regions with intermediate TB burden.

The Safety of Intra-arterial Tirofiban during Endovascular Therapy after Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: The safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA. MATERIALS AND METHODS: Using a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0-2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders. RESULTS: Among enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20-4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02-2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04-1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 -6.12; P = .099). CONCLUSIONS: Using intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.

Metformin and tuberculosis risk in elderly patients with diabetes mellitus.

SETTING: Tuberculosis (TB) and diabetes mellitus (DM) remain global health concerns. Metformin has recently received attention for its anti-tuberculosis effects.OBJECTIVE: To evaluate the risk of TB development in elderly DM patients treated with metformin compared with sulfonylureas.DESIGN: We performed a retrospective cohort study using the National Health Insurance Service-Senior database. The participants were type-2 DM (T2DM) patients aged ≥60 years between 1 January 2003 and 31 December 2013. We matched each metformin user to a sulfonylurea user using a propensity score. A Cox proportional hazards model was used to compare the risk of TB in metformin and sulfonylurea users.RESULTS: After propensity score matching, 12,582 patients were in each group. The TB incidence was 280.2/100 000 person-years (py) for metformin users and 394.5/100 000 py for sulfonylurea users. Metformin users had a lower risk of TB development than sulfonylurea users (adjusted hazard ratio 0.74, 95%CI 0.58-0.95), and the results were stronger for male participants. A dose-response relationship between metformin use and TB development was found in both sexes.CONCLUSION: Metformin use was associated with a decreased risk of TB development among elderly T2DM patients compared with sulfonylurea use.

Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents.

In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled "Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens" to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants included individuals from academia, industry, and government. This and the accompanying minireview on nonclinical PK/PD summarize the workshop discussions and recommendations. It is important to consider how information like PK/PD can support the clinical effectiveness of new antibacterial drugs, as PK/PD data have become central to antibacterial drug development programs. Key clinical considerations for antibacterial dose selection and clinical PK/PD characterization discussed in this minireview include a robust assessment of PK in the patient population of interest, critical considerations for assessing drug penetration in the lung for the treatment of pneumonia, and an emphasis on special populations, including patients with renal impairment and augmented renal function, as well as on dosing in obese and pediatric patients. Successful application of such approaches is now used to provide a more informative drug development package to support the approval of new antibiotics.

Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses.

Therapeutic drug monitoring: A patient management tool for precision medicine.

The precision medicine initiative is designed to better understand the causes of disease, to develop target therapies, and to identify patients that would benefit from treatment. Prescribing the right dose, which is not always the same to all patients, is needed for a successful outcome. The purpose of this commentary is to discuss the role of dose individualization based on therapeutic drug monitoring as a clinical patient management tool in the application of precision medicine.

Differential expression of two C-type lectins in grass carp Ctenopharyngodon idella and their response to grass carp reovirus.

The cDNAs of two C-type lectins in grass carp Ctenopharyngodon idella, galactose-binding lectin (galbl) and mannose-binding lectin (mbl), were cloned and analysed in this study. Both of them exhibited the highest expression level in liver, whereas their expression pattern differed in early phase of embryonic development. Following exposure to grass carp reovirus (GCRV), the mRNA expression level of galbl and mbl was significantly up-regulated in liver and intestine.

Day 3 versus Day 1 disseminated intravascular coagulation score among sepsis patients: a prospective observational study.

The role of disseminated intravascular coagulation (DIC) has not been extensively studied in patients with sepsis. A prospective study was performed in a single university hospital. The incidences of DIC at day 1 (<24 hours post-sepsis diagnosis) and day 3 (48 to 72 hours) were investigated among patients with sepsis. The International Society of Thrombosis and Haemostasis criteria for DIC were used. Among 381 patients initially screened, 219 were enrolled in this study and the incidences of overt DIC were 27.9% and 30.1% on day 1 and day 3, respectively. Patients with pneumonia had a lower incidence of DIC on day 1, but a higher hospital mortality rate compared to those with non-pneumonia sepsis. In multivariate models, although day 1 and day 3 DIC scores were not associated with hospital mortality after adjusting for existing severity scores, the change in DIC scores (odds ratio 1.862; 95% confidence interval 1.061 to 3.266) exhibited a significant association. Day 3 DIC scores were more accurate in predicting hospital mortality than day 1 DIC scores (P <0.001), especially in patients with non-pneumonia sepsis. However, DIC scores did not give additional discriminative power to the existing prognostic scores in predicting mortality of patients with sepsis. In conclusion, the change in DIC score was significantly associated with hospital mortality. Patients with pneumonia sepsis had a lower incidence of DIC on day 1, despite their higher disease severity and mortality rate, compared to those with other sources of sepsis.

Cultivation of a bacterial consortium with the potential to degrade total petroleum hydrocarbon using waste activated sludge.

Waste activated sludge was aerobically treated to demonstrate multiple uses such as cultivating an oil degrading bacterial consortium; studying the influence of a bulking agent (peat moss) and total petroleum hydrocarbon concentration on bacterial growth and producing a soil conditioner using waste activated sludge. After 30 days of incubation, the concentration of oil-degrading bacteria was 4.3 x 10(8) CFU g(-1) and 4.5 x 10(8) CFU g(-1) for 5 and 10 g of total petroleum hydrocarbon, respectively, in a mixture of waste activated sludge (1 kg) and peat moss (0.1 kg). This accounts for approximately 88.4 and 91.1%, respectively, of the total heterotrophic bacteria (total-HB). The addition of bulking agent enhanced total-HB population and total petroleum hydrocarbon-degrading bacterial population. Over 90% of total petroleum hydrocarbon degradation was achieved by the mixture of waste activated sludge, bulking agent and total petroleum hydrocarbon. The results of physico-chemical parameters of the compost (waste activated sludge with and without added peat moss compost) and a substantial reduction in E. coli showed that the use of this final product did not exhibit risk when used as soil conditioner. Finally, the present study demonstrated that cultivation of total petroleum hydrocarbon-degrading bacterial consortium and production of compost from waste activated sludge by aerobic treatment was feasible.

Magnetocaloric properties of TbN, DyN and HoN nanopowders prepared by the plasma arc discharge method.

We report for the first time the synthesis of nanopowders of TbN, DyN and HoN crystallized in a cubic structure by the plasma arc discharge (PAD) method and investigate their magnetocaloric properties for magnetic refrigeration applications. The nitridization of terbium, dysprosium and holmium was obtained using a mixture of nitrogen and argon gas inside a discharge chamber with 4 kPa pressure. The structural and microstructural properties of these rare earth nitrides were investigated by using X-ray diffraction and transmission electron microscopy. The studied nitrides undergo a second-order ferromagnetic to paramagnetic phase transition at Curie temperatures of 35.7, 19.9 and 14.2 K for TbN, DyN and HoN, respectively. The magnetocaloric effects were estimated by calculating the magnetic entropy changes from the magnetization data sets measured at the different applied magnetic fields and temperatures. The changes in entropy -ΔSM were found to be 12.0, 13.6 and 24.5 J kg(-1) K(-1) at an applied magnetic field of 5 T.

The influence of the earthworm Lampito mauritii (Kinberg) on the activity of selected soil enzymes in cadmium-amended soil.

The effects of cadmium (CdCl2·7H2O) on cellulase, urease, amylase, invertase and phosphatase were assessed for a period of 45 days in the presence and absence of earthworms [Lampito mauritii (Kinberg)] in alfisol soil. The activities of all enzymes significantly increased with longer incubation times (45 days) under laboratory conditions in both control and Cd-amended soils (both with and without earthworm incubation). However, the activities of all enzymes decreased with increasing Cd concentrations under laboratory conditions, both in the presence and absence of earthworms. In the presence of earthworms, cellulase, urease, invertase and amylase activities increased. However, phosphatase activity was lower in most of the Cd-amended soils in the presence of earthworms compared to its activity levels in soils lacking earthworms. These results show that earthworms modulated the stress imposed by Cd by providing suitable substrates, which in turn acted as stimulants for extracellular enzyme secretion by microbes, and by removing Cd through its accumulation in the tissues of the earthworms.

Aneurysmal subarachnoid hemorrhage causes injury of the ascending reticular activating system: relation to consciousness.

BACKGROUND AND PURPOSE: Little is known about the pathogenetic mechanism of impaired consciousness following subarachnoid hemorrhage. Using diffusion tensor imaging, we attempted to investigate the presence of injury of the lower portion of the ascending reticular activating system between the pontine reticular formation and the intralaminar thalamic nuclei, and the relation between this injury and consciousness level in patients with SAH. MATERIALS AND METHODS: We recruited 24 consecutive patients with spontaneous SAH following aneurysmal rupture and 21 healthy control subjects. Consciousness level was rated by using the Glasgow Coma Scale. Using diffusion tensor tractography, we reconstructed the lower portion of the ascending reticular activating system between the pontine reticular formation and the intralaminar thalamic nuclei. Values of fractional anisotropy, apparent diffusion coefficient, and tract number of the ascending reticular activating system were measured. RESULTS: A significant difference in the tract number was observed between the patient and control groups (P < .05); however, there was no significant difference in terms of fractional anisotropy and apparent diffusion coefficient values (P > .05). In addition, regarding the tract number of the patient group, the Glasgow Coma Scale showed strong positive correlations with the tract number on the more affected side (r = 0.890, P < .05), the less affected side (r = 0.798, P < .05), and both sides (r = 0.919, P < .05), respectively. CONCLUSIONS: We found injury of the lower portion of the ascending reticular activating system between the pontine reticular formation and the thalamus in patients with SAH. In addition, we observed a close association between injury of the lower portion of the ascending reticular activating system and impaired consciousness in patients with SAH.

Lichen planus pemphigoides associated with chronic hepatitis B virus infection.

Lichen planus pemphigoides (LPP) is a rare autoimmune dermatosis with the features of both lichen planus (LP) and bullous pemphigoid (BP). Although in rare cases, LPP has been associated with several medications and conditions, it is generally considered an idiopathic disorder, and its pathogenesis remains uncertain. We report a 56-year-old woman who presented with a 2-year history of flat-topped, polygonal, violaceous-colored papules and some bullae. She was diagnosed with chronic hepatitis B virus (HBV) infection, which had been treated intermittently with entecavir. Histopathological examination showed the typical features of LP with subepidermal blisters, and with linear deposits of IgG along the basement membrane zone on direct immunofluorescence. Immunoblotting revealed antibodies directed at the BP180 and BP230 antigens. We diagnosed the patient with LPP, and treated the condition with systemic steroids and dapsone. To our knowledge, this is the first report of LPP in a patient with chronic HBV infection.

Different characteristics of the corticospinal tract according to the cerebral origin: DTI study.

BACKGROUND AND PURPOSE: Little is known about differences in corticospinal tract fibers according to cerebral origin. Using diffusion tensor tractography, we attempted to investigate the characteristics of the CST according to the cerebral origin in the human brain. MATERIALS AND METHODS: Thirty-six healthy subjects were recruited for this study. A 1.5T Gyroscan Intera system was used for acquisition of DTI. CSTs were reconstructed by selection of fibers passing through seed and target ROIs: seed ROIs, the area of the CST at the pontomedullary junction; target ROIs, the primary motor cortex, the primary somatosensory cortex, the dorsal premotor cortex, and the supplementary motor area. RESULTS: A significant difference in tract volume was observed in each ROI (P < .05): M1 (2373.6, 36.9%), S1 (2037.7, 31.7%), SMA (1588.0, 24.7%), and dPMC (429.8, 6.7%). Regarding fractional anisotropy values, the dPMC or SMA showed higher values than the M1 or S1; however, the opposite occurred in terms of the mean diffusivity value (P < .05). In addition, fractional anisotropy and mean diffusivity values of the dPMC differed from those of the SMA (P < .05); in contrast, no significant difference was observed between the M1 and S1 (P > .05). CONCLUSIONS: Tract volume was found to differ according to cerebral origin and was, in descending order, M1, S1, SMA, and dPMC. In addition, the directionality and diffusivity of CST fibers in the SMA and the dPMC differed from those of the M1 and S1, which showed similar characteristics.

Diffusion tensor imaging-demonstrated differences between hemiplegic and diplegic cerebral palsy with symmetric periventricular leukomalacia.

BACKGROUND AND PURPOSE: Patients with cerebral palsy have variable clinical presentations such as hemiplegic, diplegic, or quadriplegic patterns though they have PVL on conventional MR images. The authors investigated whether DTT can differentiate between hemiplegic and diplegic CP in patients presenting with symmetric PVL on conventional MR images. MATERIALS AND METHODS: One hundred thirteen consecutive pediatric patients with definite hemiplegic (59 patients; 30 boys, 29 girls; mean age, 34.19 months; range, 24-52 months) or diplegic (54 patients; 27 boys, 27 girls; mean age, 31.07 months; range, 24-48 months) symptoms and bilateral symmetric PVL on conventional brain MR imaging were recruited. The states of CSTs were examined by using DTT, and the asymmetries of right and left CSTs in the hemiplegic and diplegic groups were compared by using asymmetric anisotropy indexes and asymmetric mean diffusivity indexes. RESULTS: All patients in the hemiplegic group with asymmetric results exhibited disrupted integrities of more affected CSTs and sparing of less affected CSTs. However, diplegic patients revealed symmetric disrupted findings of the right and left CSTs at the upper periventricular level. Asymmetric anisotropy index and asymmetric mean diffusivity index values were significantly higher in the hemiplegic group than in the diplegic group (P < .05), and these results of DTT significantly corresponded with their typical clinical manifestation. CONCLUSIONS: DTT may be very useful for the detailed estimation of the CST state in patients with bilateral symmetric PVL.