Effects of Arterial Stiffness on Cerebral WM Integrity in Older Adults: A Neurite Orientation Dispersion and Density Imaging and Magnetization Transfer Saturation Imaging Study.

BACKGROUND AND PURPOSE: Arterial stiffness is reported to be able to cause axonal demyelination or degeneration. The present study aimed to use advanced MR imaging techniques to examine the effect of arterial stiffness on the WM microstructure among older adults. MATERIALS AND METHODS: Arterial stiffness was measured using the cardio-ankle vascular elasticity index (CAVI). The high-CAVI (mean CAVI ≥ 9 points) and the low-CAVI groups (mean CAVI < 9 points) were created. The neuronal fiber integrity of the WM was evaluated by neurite orientation dispersion and density imaging and magnetization transfer saturation imaging. Tract-Based Spatial Statistics and the tracts-of-interest analysis were performed. Specific WM regions (corpus callosum, internal capsule, anterior thalamic radiation, corona radiata, superior longitudinal fasciculus, forceps minor, and inferior fronto-occipital fasciculus) were selected in the tracts-of-interest analysis. RESULTS: In Tract-Based Spatial Statistics, the high-CAVI group showed a significantly lower myelin volume fraction value in the broad WM and significantly higher radial diffusivity and isotropic volume fraction values in the corpus callosum, forceps minor, inferior fronto-occipital fasciculus, internal capsule, corona radiata, and anterior thalamic radiation than the low-CAVI group. In tracts-of-interest analysis using multivariate linear regression, significant associations were found between the mean CAVI and radial diffusivity in the anterior thalamic radiation and the corona radiata; isotropic volume fraction in the anterior thalamic radiation and the corona radiata; and myelin volume fraction in the superior longitudinal fasciculus (P < .05). Additionally, partial correlation coefficients were observed for the significant associations of executive function with radial diffusivity and myelin volume fraction (P < .05). CONCLUSIONS: Arterial stiffness could be associated with demyelination rather than axonal degeneration.

An Investigation of Water Diffusivity Changes along the Perivascular Space in Elderly Subjects with Hypertension.

BACKGROUND AND PURPOSE: Hypertension may be related to alterations of the glymphatic system, a waste metabolite drainage system in the brain. We aimed to investigate analysis along the perivascular space index changes in elderly subjects with hypertension. MATERIALS AND METHODS: Diffusion-weighted images were acquired from 126 subjects, including 63 subjects with hypertension (25 men and 38 women; mean age, 72.45 years) and 63 age- and sex-matched controls (25 men and 38 women; mean age, 72.16 years). We calculated the analysis along the perivascular space index as a ratio of the mean of x-axis diffusivities in the projection and association areas to the mean of y-axis diffusivity in the projection area and z-axis diffusivity in the association area. The left, right, and mean analysis along the perivascular space indices of both hemispheres were compared between the hypertension and control groups using a Mann-Whitney U test. The Spearman correlation coefficient was used to assess the correlation between the left, right, and mean ALPS indices and blood pressure and pulse pressure. RESULTS: The left (P = .011) and mean (P = .024) analysis along the perivascular space indices of the hypertension group were significantly lower than that of the control group. The left, right, and mean analysis along the perivascular space indices of all subjects were significantly negatively correlated with blood pressure values (r = -0.200 to -0.278, P = .002-0.046) and pulse pressure values (r = -0.221 to -0.245, P = .006-0.013). CONCLUSIONS: Our results are consistent with a model in which hypertension causes glymphatic dysfunction.

Feasibility of virtual surgical simulation in the head and neck region for soft tissue reconstruction using free flap: a comparison of preoperative and postoperative volume measurement.

In the head and neck region, preoperative evaluation of the free flap volume is challenging. The current study validated preoperative three-dimensional (3D) virtual surgical simulation for soft tissue reconstruction by assessing flap volume and evaluated fat and muscle volume changes at follow-up in 13 head and neck cancer patients undergoing anterolateral craniofacial resection. Patients received 3D virtual surgical simulation, and the volume of the planned defects was estimated by surgical simulation. Following en bloc resection of the tumor, the defect in the skull base was covered using a rectus abdominis myocutaneous flap. Following surgery, computed tomography scans were acquired at day 1 and at 6 and 12 months. Virtual planned defect was on average 227 ml (range, 154-315) and was 10% smaller than the actual flap volume in patients without skin involvement of the tumor. Between day 1 and 12 months post-surgery, the volume of fat and muscle tissue in the free flap dropped by 9% and 58%, respectively. Our results indicate that 3D virtual surgical simulation provides essential information in determining the accurate volume of the required free flap for surgical defect repair and may thus help improve surgical planning and functional and esthetic outcome.

Development and validation of antisnake venom knowledge assessment tool (AKAT) for healthcare practitioners.

Antisnake venom (ASV) is the only specific and standard treatment for snakebite envenoming worldwide. The knowledge of antivenom dosage, mode of administration, availability, and logistics is essential to the healthcare practitioners (HCPs) in the management of snakebites. It is vital for the HCPs involved in the handling of ASVs to have its basic knowledge. The ASV contains proteins and can, therefore, easily get denatured if not handled appropriately, leading to poor therapeutic outcome. It is also essential for clinicians to be aware of the tendency of ASV to cause a severe life-threatening hypersensitivity reaction. There is currently no validated tool for assessing the knowledge of ASV among HCPs. Therefore, we developed and validated a tool for evaluating the HCPs knowledge of ASV. The items included in the tool were first generated from a comprehensive literature review. Face validity were conducted by presenting the drafted tool to ten experts on the subject matter. A validation study was conducted among doctors, pharmacists, nurses, pharmacy technicians, and the general public. The objectives of the study were to test the tool for content validity using the content validity index (CVI), construct validity using contrast group approach, difficulty index, readability, and reliability test using the test-retest method. We developed and validated a final tool containing thirty-three items. The tool was valid for face validity and had a scale-level (average) content validity (S-CVI/Ave) of 0.91. The ASV knowledge of pharmacists was higher than that of doctors, pharmacy technicians, nurses, and the general public (p < 0.001), thus, valid for construct validity. The readability of the tool using the Simple Measure of Gobbledygook (SMOG) was determined to be grade level 7. The test-retest analysis showed no significant difference between the mean knowledge scores measured at four weeks interval (p = 0.916), implying excellent reliability. The AKAT has demonstrated good psychometrical properties that would enable its application among a wide range of healthcare practitioners.

Knowledge assessment of snake antivenom among healthcare practitioners involving educational intervention in northern Nigeria: a study protocol.

INTRODUCTION: Snakebite envenoming (SBE) is an important occupational and public health hazard especially in sub-Saharan Africa. For optimum management of SBE, adequate knowledge of Snake antivenom (SAV) is very critical among the healthcare practioners in this region. Information related to the knowledge of SAV use in the management of SBE, as well as SAV logistics is scarce among the Health Care Professionals (HCPs) in Nigeria, particularly in the northern region. We therefore aimed to develop, validate and utilize a tool to assess the SAV knowlegde among HCPs in northern Nigeria. We also sought to implement and evaluate an intervention that could improve the SAV knowledge among the HCPs. METHODS: The proposed study will be conducted in three phases: Phase I will involve the development of the item-pool to be included in the tool, followed by a face, content validity and construct validity. The tool reliability, readability and difficulty index will be determined. Phase II will involve the utilization of the tool to assess baseline SAV knowledge among the HCPs followed by an educational intervention. Multiple Linear Regression analysis will be used to determine the factors associated with SAV knowledge among the HCPs. Lastly, Phase III which will be a repeat of Phase II to assess and evaluate the knowledge after the intervention. DISCUSSION: The study design and findings may guide future implementation and streamline the intervention of improving SAV knowledge in HCPs training and practice. LAY SUMMARY: Knowledge assessment and educational intervention of snake antivenom among healthcare practitioners in northern Nigeria: a study protocol Snakebite envenoming (SBE) is an important occupational and public health hazard especially in sub-Saharan Africa. For optimum management of SBE, adequate knowledge of snake antivenom (SAV) is very critical among the healthcare practitioners. The baseline knowledge SAV dosage, mode of administration, availability, and logistics is very relevant among healthcare professionals, particularly those that are directly involved in its logistics. It is paramount that SAV is handled and used appropriately. The efforts and advocacy for the availability for more SAV will be in vain if not handled appropriately before they are used. This study protocol aims to develop a tool, to assess SAV knowledge and effects of educational interventions among healthcare professionals (HCPs) in northern Nigeria. This protocol suggests conducting studies in three phases: (a) Development and validation of SAV knowledge assessment tool, (b) Baseline assessment of SAV knowledge assessment tool among HCPs, and (c) Development, implementation and evaluation of an educational intervention to improve SAV knowledge among HCPs in northern Nigeria.

Effects of Rice Wine Lees on Cognitive Function in Community-Dwelling Physically Active Older Adults: A Pilot Randomized Controlled Trial.

BACKGROUND: Rice wine lees (RWL), a Japanese traditional fermented product, is a rich source of one-carbon metabolism-related nutrients, which may have beneficial effects on cognitive function. OBJECTIVES: We aimed to examine the effect of the RWL on cognitive function in community-dwelling physically active older adults. DESIGN: Double-blind, randomized, placebo-controlled study (clinical trial number: UMIN 000027158). SETTING: Community-based intervention including assessments conducted at the University of Hyogo and a public liberal arts school in Himeji City, Japan. PARTICIPANTS: A total of 35 community-dwelling older adults (68-80 years) who performed mild exercise before and during the trial were assigned to either the RWL (n=17) or the placebo group (n=18). INTERVENTION: Daily consumption of 50 g RWL powder, which contained one-carbon metabolism-related nutrients, or the placebo powder (made from soy protein and dextrin) for 12 weeks. Both supplements included equivalent amounts of energy and protein. MEASUREMENTS: Montreal Cognitive Assessment, computerized cognitive function test, and measurements of serum predictive biomarkers (transthyretin, apolipoprotein A1, and complement C3) were conducted at baseline and follow-up. RESULTS: Visual selective attention and serum transthyretin significantly improved in the RWL group, whereas there was no significant change in the placebo group. No significant group difference was observed in the remaining cognitive performance tests. CONCLUSIONS: RWL supplements seem to have a few effects on cognitive function in community-dwelling physically active older adults. However, the impact was limited; therefore, further studies with sufficient sample size are warranted to elucidate this issue.

White Matter Abnormalities in Multiple Sclerosis Evaluated by Quantitative Synthetic MRI, Diffusion Tensor Imaging, and Neurite Orientation Dispersion and Density Imaging.

BACKGROUND AND PURPOSE: A number of MR-derived quantitative metrics have been suggested to assess the pathophysiology of MS, but the reports about combined analyses of these metrics are scarce. Our aim was to assess the spatial distribution of parameters for white matter myelin and axon integrity in patients with relapsing-remitting MS by multiparametric MR imaging. MATERIALS AND METHODS: Twenty-four patients with relapsing-remitting MS and 24 age- and sex-matched controls were prospectively scanned by quantitative synthetic and 2-shell diffusion MR imaging. Synthetic MR imaging data were used to retrieve relaxometry parameters (R1 and R2 relaxation rates and proton density) and myelin volume fraction. Diffusion tensor metrics (fractional anisotropy and mean, axial, and radial diffusivity) and neurite orientation and dispersion index metrics (intracellular volume fraction, isotropic volume fraction, and orientation dispersion index) were retrieved from diffusion MR imaging data. These data were analyzed using Tract-Based Spatial Statistics. RESULTS: Patients with MS showed significantly lower fractional anisotropy and myelin volume fraction and higher isotropic volume fraction in widespread white matter areas. Areas with different isotropic volume fractions were included within areas with lower fractional anisotropy. Myelin volume fraction showed no significant difference in some areas with significantly decreased fractional anisotropy in MS, including in the genu of the corpus callosum and bilateral anterior corona radiata, whereas myelin volume fraction was significantly decreased in some areas where fractional anisotropy showed no significant difference, including the bilateral posterior limb of the internal capsule, external capsule, sagittal striatum, fornix, and uncinate fasciculus. CONCLUSIONS: We found differences in spatial distribution of abnormality in fractional anisotropy, isotropic volume fraction, and myelin volume fraction distribution in MS, which might be useful for characterizing white matter in patients with MS.

Use of traditional medicines among pharmacists in Nigeria.

BACKGROUND: Traditional Medicine (TM) use is growing and emerging as an issue of public healthcare importance. Recently, there are increasing interest and trends of TM use among health care professionals (HCP). However, information regarding TM use among pharmacists in Nigeria is limited. This study investigates the use of TM among pharmacists in Nigeria. MATERIALS AND METHODS: This study was a cross sectional study in the form of an online survey (Google Surveys). Eligible participants were pharmacists currently practicing in Nigeria. The closed-ended questionnaire was developed and validated prior to the data collection. The hyperlink to the online survey questionnaire was shared with the eligible pharmacists via social media groups belonging to pharmacists' professional associations. RESULTS: A total of 262 of completed responses were received. Among the respondents, 53.2% had over 5 years of pharmacy practice experience and 48% were practicing in hospitals. 225 respondents (85.9%) have ever used TM at least once in their lifetime, while 21.3% were currently using TM at the time of the data collection. Those that used TM in the last 12 months were 47.0%, while those that used it within the last week, one month and six months were 15.4%, 10.5% and. 12.8% respectively. Herbal medicine was the most frequently used TM among the respondents (94.2%). The most common reason for using TM was for the maintenance of general well-being (38.2%). Among the TM users, 17.3% have reported experiencing an ADE-related to the TM use. Among the respondents, 44.7% felt TM is safe for use while 35.5% indicated that they will recommend TM to their patients. CONCLUSION: TM is commonly used by a pharmacist in Nigeria particularly among those practicing in the community and hospital. This signifies an increasing acceptance of TM among healthcare professionals and a call for more education and training on TM for effective pharmaceutical care delivery.

Improving the Quality of Synthetic FLAIR Images with Deep Learning Using a Conditional Generative Adversarial Network for Pixel-by-Pixel Image Translation.

BACKGROUND AND PURPOSE: Synthetic FLAIR images are of lower quality than conventional FLAIR images. Here, we aimed to improve the synthetic FLAIR image quality using deep learning with pixel-by-pixel translation through conditional generative adversarial network training. MATERIALS AND METHODS: Forty patients with MS were prospectively included and scanned (3T) to acquire synthetic MR imaging and conventional FLAIR images. Synthetic FLAIR images were created with the SyMRI software. Acquired data were divided into 30 training and 10 test datasets. A conditional generative adversarial network was trained to generate improved FLAIR images from raw synthetic MR imaging data using conventional FLAIR images as targets. The peak signal-to-noise ratio, normalized root mean square error, and the Dice index of MS lesion maps were calculated for synthetic and deep learning FLAIR images against conventional FLAIR images, respectively. Lesion conspicuity and the existence of artifacts were visually assessed. RESULTS: The peak signal-to-noise ratio and normalized root mean square error were significantly higher and lower, respectively, in generated-versus-synthetic FLAIR images in aggregate intracranial tissues and all tissue segments (all P < .001). The Dice index of lesion maps and visual lesion conspicuity were comparable between generated and synthetic FLAIR images (P = 1 and .59, respectively). Generated FLAIR images showed fewer granular artifacts (P = .003) and swelling artifacts (in all cases) than synthetic FLAIR images. CONCLUSIONS: Using deep learning, we improved the synthetic FLAIR image quality by generating FLAIR images that have contrast closer to that of conventional FLAIR images and fewer granular and swelling artifacts, while preserving the lesion contrast.

Effect of Gadolinium on the Estimation of Myelin and Brain Tissue Volumes Based on Quantitative Synthetic MRI.

BACKGROUND AND PURPOSE: The effect of gadolinium on the estimation of myelin has not been reported. The aim of the current study was to investigate the effects of gadolinium on automatic myelin and brain tissue volumetry via quantitative synthetic MR imaging. MATERIALS AND METHODS: The study included 36 patients who were referred for brain metastases screening, and quantitative synthetic MR imaging data before and after gadolinium-based contrast agent administration were analyzed retrospectively. Brain metastases were detected in 17 patients. WM volume, GM volume, CSF volume, non-WM/GM/CSF volume, myelin volume, brain parenchymal volume, myelin fraction (myelin volume/brain parenchymal volume), and intracranial volume were estimated. T1 and T2 relaxation times, proton density, and myelin partial volume per voxel averaged across the brain parenchyma were also analyzed. RESULTS: In patients with and without metastases after gadolinium-based contrast agent administration, measurements of WM and myelin volumes, and myelin fraction were significantly increased (+26.65 and +29.42 mL, +10.14 and +12.46 mL, +0.88% and +1.09%, respectively), whereas measurements of GM, CSF, brain parenchymal, and intracranial volumes were significantly decreased (-36.23 and -34.49 mL, -20.77 and -18.94 mL, -6.76 and -2.84 mL, -27.41 and -21.84 mL, respectively). Non-WM/GM/CSF volume did not show a significant change. T1, T2, and proton density were significantly decreased (-51.34 and -46.84 ms, -2.67 and -4.70 ms, -1.05%, and -1.28%, respectively) after gadolinium-based contrast agent administration, whereas measurements of myelin partial volume were significantly increased (+0.78% and +0.75%, respectively). CONCLUSIONS: Gadolinium had a significant effect on the automatic calculation of myelin and brain tissue volumes using quantitative synthetic MR imaging, which can be explained by decreases in T1, T2, and proton density.

Nitrogen balance in patients with hemiparetic stroke during the subacute rehabilitation phase.

BACKGROUND: In highly invasive diseases, metabolism commonly changes. Hypercatabolism is frequent in acute stroke, and nitrogen balance tends to be negative. However, there has been no study describing nitrogen balance in subacute and chronic stroke patients. The present study aimed to examine nitrogen balance in the subacute and chronic phases and to identify the factors related to it. METHODS: Nitrogen balance was calculated from the collected urine of 56 patients with subacute stroke [mean (SD) 53.8 (18.4) days post-stroke] who were admitted for rehabilitation for their first-ever ischaemic or nonsurgical haemorrhagic stroke. In the first experiment, their nitrogen balance was measured during the rehabilitation phase, and factors (type, severity of hemiparesis, activities of daily living, dysphagia and malnutrition status) related to it were evaluated. The second experiment was performed to describe the time course of nitrogen balance in 31 consecutive patients, with assessments made at admission and at discharge. RESULTS: Nitrogen balance was positive in all patients in the subacute phase. A significant difference was seen in nitrogen balance between high and low fat-free mass in male patients. In the chronic phase, nitrogen balance was positive in 96% of the patients. There was no significant difference in nitrogen balance between discharge and admission. CONCLUSIONS: In the subacute and chronic phases of stroke, it was confirmed that hypercatabolism had resolved and that intensive rehabilitation is possible in the convalescent period of stroke.

Ipragliflozin as an Initial Therapy in Drug Naïve Subjects with Type 2 Diabetes.

OBJECTIVES: The aim of this study is to investigate ipragliflozin as an initial type 2 diabetes (T2DM) drug. METHODS: Ipragliflozin 25-50 mg/day monotherapy was performed with drug naïve subjects with T2DM (n=31). As a comparator, 12.5-25 mg/day alogliptin monotherapy was undertaken (n=32). At 3 months, levels of metabolic parameters were compared with those at baseline. FINDINGS: 4 subjects discontinued ipragliflozin due to intolerance or adverse events, while none dropped out with alogliptin. At 3 months, similar decreases of HbA1c levels were observed with these 2 drugs (10.21-8.31%, p<0.00001, with ipragliflozin, and 10.08-8.25%, p<0.00001, with alogliptin), however fasting blood glucose (FBG) levels decreased with significant inter-group differences (- 23.5% with iprgliflozin and - 10.8% with alogliptin). While similar increases of homeostasis model assessment (HOMA)-B levels were observed with these 2 drugs, HOMA-R levels significantly decreased only with ipragliflozin (-19.4%, p<0.02). Un-correlative link between HOMA-R and HOMA-B levels at baseline became significantly correlative (R=0.6017, p<0.001) only with ipragliflozin. Significant reductions of body mass index (BMI, -2.6%, P<0.05) were observed with ipragliflozin, however, no correlations between the changes of BMI and those of HbA1c or FBG were noted. CONCLUSIONS: These results suggest that ipragliflozin has good glycemic efficacy as an initial therapy in subjects with T2DM, although certain adverse events or tolerability issues are concerned. It improves insulin sensitivity and may restore the impaired beta-cell function. However body weight reduction with ipragliflozin is not associated with its glycemic efficacy.

Distinct glucose-lowering properties in good responders treated with sitagliptin and alogliptin.

BACKGROUND AND OBJECTIVES: All dipeptidyl peptidase 4 (DPP-4) inhibitors display similar glycemic efficacies, although they differ greatly in their chemical structures and pharmacological properties. This may be due to the inclusions of non- or poor-responders in the analysis, thereby masking the real effects of these drugs. The aim of this study was to identify any differences in diabetic parameters only in good responders treated with sitagliptin and alogliptin. METHODS: Treatment naïve subjects with type 2 diabetes mellitus were assigned to either sitagliptin 25-50 mg/day (n = 69) or alogliptin 12.5-25 mg/day monotherapy (n = 62) for 3 months. Only those who showed good response selected by a novel parameter called A1c index were further analysed (n = 24 for sitagliptin and n = 21 for alogliptin). RESULTS: At baseline, FBG and BMI were significantly higher and CPR-index was significantly lower in alogliptin good responders. At 3 months, while similar reductions of HbA1c were observed in these two groups, decreases of fasting blood glucose (FBG) were significantly higher in alogliptin good responders. Homeostasis model assessment (HOMA)-R significantly decreased only in alogliptin good responders, while HOMA-B similarly and significantly increased in these two groups. BMI significantly increased only in sitagliptin good responders. Significant negative correlations were observed between A1c index and changes (Δ) of HOMA-B in both groups. By contrast, significant positive and negative correlations were observed between ΔFBG and ΔHOMA-R, and between ΔFBG and ΔHOMA-B, respectively, only in alogliptin good responders. CONCLUSIONS: These results implicate that the effects on diabetic parameters and the glucose-lowering mechanisms of these two drugs might be different in those who have good response with these drugs. Accordingly, the choice of these drugs may be dependent on the characteristics of the patients.

A novel HLA-B allele, HLA-B*44:184, identified by super high-resolution single-molecule sequence-based typing in a Japanese individual.

The novel allele HLA-B*44:184 differs from HLA-B*44:77 by three non-synonymous amino acid exchanges, T94I, L95I and S97R.

Incidence of childhood pneumonia and serotype and sequence-type distribution in Streptococcus pneumoniae isolates in Japan.

The 7-valent pneumococcal conjugate vaccine (PCV7) is reported to decrease the incidence of community-acquired pneumonia (CAP) in children. To determine the annual incidence of CAP before the introduction of PCV7, we counted the number of children hospitalized with CAP between 2008 and 2009 in Chiba City, Japan. We investigated serotype and multilocus sequence typing (MLST) for Streptococcus pneumoniae isolates in CAP cases. The annual incidence of hospitalized CAP in children aged <5 years was 17.6 episodes/1000 child-years. In 626 episodes, S. pneumoniae was dominant in 14.7% and 0.8% of sputum and blood samples, respectively. The most common serotypes were 6B, 23F and 19F. The coverage rates of PCV7 were 66.7% and 80% in sputum samples and blood samples, respectively. MLST analysis revealed 37 sequence types. Furthermore, 54.1% of the sputum isolates and 40% of the blood isolate were related to international multidrug-resistant clones.

Anti-obesity compounds in green leaves of Eucommia ulmoides.

The anti-hypertensive effect of Eucommia leaves has been confirmed clinically, and the study of their anti-obesity properties has advanced. However, the compounds involved in their anti-obesity effect have not been fully elucidated. In this Letter, we examined the anti-obesity effect of Eucommia green leaf extract (EGLE) divided into five fractions with high porous polystyrene gel and of the compounds isolated, geniposidic acid, asperuloside and chlorogenic acid, respectively. A metabolic syndrome-like clinical model in mice was generated by feeding a 40% high-fat diet to examine the anti-obesity effects of chronic administration of test substance. After 4 weeks, body weight, white adipose tissue weight, plasma triglyceride levels and total cholesterol levels in the model mice were significantly inhibited by the 30% MeOH fraction (containing much higher levels of asperuloside than the other fractions), and these effects were similar to those of EGLE. Chronic administration of isolated asperuloside in Eucommia leaves suppressed increases in model mouse body weight, white adipose tissue weight, plasma triglyceride levels and free fatty acids levels. These results suggest that asperuloside in Eucommia leaves has important anti-obesity effects.

Detection of Human papillomavirus and cellular regulators p16INK4a, p53, and NF-kappaB in penile cancer cases in Kenya.

Human papillomavirus (HPV) E6 and E7 gene products play a central role in the induction of benign proliferation and malignant transformation by interacting with several cellular regulatory proteins such as p53, p16(INK4a), and nuclear factor kappaB (NF-kappaB). In this study, HPV DNA was detected by in situ hybridization (ISH) and p53, p16(INK4a), and NF-kappaB by immunochemistry in 22 penile cancer cases in Kenya. HPV DNA was found in 68.2% of the cases. There was no difference in the p53- and p16(INK4a)-positivities in HPV DNA-positive and HPV DNA-negative cases. In HPV DNA-positive cases, the NF-kappaB positivity in the nucleus, cytoplasm, and nucleus and/or cytoplasm amounted to 73.3%, 93.3%, and 100%, respectively, while in HPV DNA-negative cases, a 28.7% NF-kappaB positivity of in the nucleus and/or cytoplasm was observed. It is concluded that NF-kappaB in penile cancer is expressed more frequently in the presence of HPV infection than in its absence.

Radiation-induced xerostomia: objective evaluation of salivary gland injury using MR sialography.

BACKGROUND AND PURPOSE: Xerostomia (dry mouth) is one of the serious complications of head and neck irradiation and has a strong influence on a patient's activities of daily living. MR sialography with salivary secretion stimulation provides additional functional information (salivary secretion reserve) and may contribute to the evaluation of the severity of xerostomia and predict the risk of developing a radiation-induced xerostomia. This aim of the study was to analyze MR sialography as an objective tool to evaluate radiation-induced salivary injury. MATERIALS AND METHODS: MR sialography with salivary secretion stimulation was performed in 16 patients with head and neck malignancy before and after irradiation therapy. Multivariate (stepwise multiple regression) analysis was performed to analyze the nonstimulated and stimulated MR sialography findings and the clinical severity of xerostomia. RESULTS: Multivariate analysis of the preirradiation study revealed no significant independent variables that could predict the clinical severity of xerostomia. In the postirradiation study, following regression with 2 independent variables (secretion response of the submandibular gland [rSG] and parotid gland visualization on stimulated MR sialography [sPG]) could explain 70% of the cases: xerostomia severity grade = 0.681 + 0.871 x rSG - 0.471 x sPG. CONCLUSIONS: MR sialography is a useful method for visualization of salivary gland radiation injury and estimation of the severity of radiation-induced xerostomia. Insufficiency of secretion reserve at the irradiated submandibular gland has the strongest influence on xerostomia severity. Our investigation suggests that careful submandibular gland protection may lead to prevention and avoidance of radiation-induced xerostomia.