In vivo phosphorus polarization transfer and decoupling from protons in three-dimensional localized nuclear magnetic resonance spectroscopy of human brain

Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from protons (¹H) to a J-coupled phosphorus (³¹P) has been incorporated into three-dimensional (3D) chemical-shift-imaging (CSI) sequence on a clinical imager. The technique is demonstrated on a phantom and in in vivo human brain. The polarization-transfer efficiency (～1.2) is lower than the theoretical maximum of γ¹H/γ³¹P≈ 2.4 resulting from ¹H-¹H homonuclear J couplings of similar magnitude competing with the ¹H →³¹P transfer. Nevertheless, compared with direct ³¹P Ernst-angle excitation, signal gains of up to × 1.8 were obtained mainly as a result of T¹ differences between ³¹P and the ¹H. Spectral interpretation is simplified by editing out all non-proton-coupled ³¹P signals. The duration, ～50 min, and power deposition, ～1 W · kg^?1, make the application suitable for human studies.     

DFNB40, a recessive form of sensorineural hearing loss, maps to chromosome 22q11.21-12.1

We report on a novel localization for a recessive form of deafness (DFNB), by linkage analysis in an Iranian consanguineous family. Affected individuals suffer from prelingual profound sensorineural hearing loss. Genome-wide analysis led to the characterization of a new locus, DFNB40, which maps to an approximately 9 Mb interval between markers D22S427 and D22S1144 at chromosome 22q11.21-12.1. Maximum lod score of 3.09 was obtained with D22S1174. Since the Bronx waltzer (bv) mouse mutant, characterized by waltzing behavior, deafness, and degeneration of cochlear inner hair cells, has been mapped to the syntenic region on murine chromosome 5, we suggest that DFNB40 and bv may result from orthologous gene defects.     

Gait speed is more challenging than cognitive load on the stride-to-stride variability in individuals with anterior cruciate ligament deficiency

Background

Several investigations have studied gait variability of individuals with anterior cruciate ligament (ACL) deficiency; however, the effect of dual-tasking on the gait variability of these individuals remained unclear. The aim of the present study was to determine the effect of gait speed and dual-tasking on knee flexion–extension variability in subjects with and without ACL deficiency.

Spinal Manipulation for Subacute and Chronic Lumbar Radiculopathy: A Randomized Controlled Trial

ObjectiveWe evaluated the efficacy of spinal manipulation for the management of nonacute lumbar radiculopathy.MethodsIn a university hospital we performed a randomized controlled trial with 2 parallel arms. Patients (n = 44) with unilateral radicular low back pain lasting more than 4 weeks were randomly allocated to manipulation and control groups. The primary outcome was the intensity of the low back pain on a visual analog scale. The secondary outcome was the Oswestry Disability Questionnaire score. We also measured spinal ranges of motion. The assessments were carried out at the baseline, immediately after intervention, and at 3 months’ follow-up. All patients underwent physiotherapy. The manipulation group received three sessions of manipulation therapy 1 week apart. For manipulation, we used Robert Maigne's technique.ResultsBoth groups experienced a decrease in back and leg pain significantly (all P ≤ 0.003). However, only the manipulation group showed significantly favorable results in the Oswestry scores (P < 0.001), and the straight leg raise test (P = 0.001). All ranges of motion increased significantly with manipulation (all P < 0.001), but the control group showed favorable results only in right and left rotations and in extension (all P < 0.001). Between-group analyses showed significantly better outcomes for manipulation in all measurements (all P ≤ 0.009) with large effect sizes.ConclusionSpinal manipulation improves the results of physiotherapy over a period of 3 months for patients with subacute or chronic lumbar radiculopathy.     

Healthy ranges of serum alanine aminotransferase levels in Iranian blood donors

AIM: The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors. METHODS: A total of 1,939 blood donors were included. ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels. RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L, and for non-overweight men was 40 U/L. CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

Healthy ranges of serum alanine aminotransferase levels in Tranian blood donors

AIM:The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors.METHODS: A total of 1 939 blood donors were included.ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels.RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L,and for non-overweight men was 40 U/L.CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

Delivery and Biodistribution of Traceable Polymeric Micellar Diclofenac in the Rat

The nonsteroidal anti-inflammatory drugs elevate cardiovascular risk, perhaps, due to their accumulation in the heart and kidneys. We designed nanodelivery systems for cardiotoxic diclofenac to reduce its presence in these organs. Diclofenac ethyl ester (DFEE) was encapsulated in traceable micelles based on poly(ethylene oxide)-b-poly(ε-caprolactone) (DFEE-PCL-TM) or poly(ethylene oxide)-b-poly(α-benzyl carboxylate-ε-caprolactone) (DFEE-PBCL-TM). Diclofenac pharmacokinetics and tissue distribution were studied after intravenous (iv) and intraperitoneal administration of the nanoformulations and compared with those after iv doses of free diclofenac (n = 3-6/group). The average diameters for DFEE-PBCL-TM and DFEE-PCL-TM were 37.2 ± 0.06 and 45.1 ± 0.06 nm, respectively. Drug concentration dropped below the assay sensitivity after free drug administration in 6 h, but persisted for 24 h following DFEE-PBCL-TM (2.3 ± 1.4 μg/mL) and DFEE-PCL-TM (1.9 ± 0.6 μg/mL) iv administration. The diclofenac heart:blood and kidney:blood ratios were 5- to 12-fold lower with the nanoformulations than with free diclofenac. Near-infrared fluorescence measurements in tissues suggested exposure patterns to nanocarriers parallel with those achieved for delivered diclofenac by nanoformulations. Administration of DFEE-PCL-TM by iv or intraperitoneal injection, resulted in comparable pharmacokinetics and 6 h postdose near-infrared fluorescence in the heart, kidneys, liver, and spleen. When compared to each other, DFEE-PBCL-TM showed significantly lower diclofenac levels in the heart compared to DFEE-PCL-TM (0.3 ± 0.03 vs. 0.5 ± 0.1 μg/g). Developed nanoformulations of diclofenac prolonged diclofenac circulation and reduced its presence in the heart and kidneys, strongly suggesting cardiac-safe delivery vehicles for diclofenac.     

Lack of Association Between Transforming Growth Factor Beta 1 -509C/T and +915G/C Polymorphisms and Chronic Hepatitis B in Iranian Patients

Background:

Chronic hepatitis B is one of the world''s major health concern. The etiological agent of this infection is hepatitis B virus (HBV), which can evade the immune system response. Transforming growth factor beta 1 (TGF-β1) can act against HBV by suppressing the viral replication. The TGF-β1 also plays an important role in preventing liver damage in chronically HBV infected patients.

Objectives:

In this study, the association of TGF-β1 +915G/C and -509C/T gene polymorphisms with chronic hepatitis B was evaluated in Iranian patients.

Materials and Methods:

A population-based case–control study was conducted in Taleghani Hospital, Tehran. A number of 220 patients with chronic hepatitis B and the same number of healthy control subjects were designated the case and the control groups. The PCR-Restriction Fragment Length Polymorphism Method (PCR-RFLP) method was used for genotyping both polymorphisms. Ten percent of the control samples were sequenced to confirm the results.

Results:

No statically significant differences in genotype distribution and allele frequency were observed for both polymorphisms between healthy controls and patients with chronic hepatitis B.

Conclusions:

There was no association between TGF-β1 -509C/T and +915G/C polymorphisms with chronic hepatitis B and it seems that these changes don not play a significant role in increasing the risk of chronic infection in Iranian patients.