Lead exposure and intelligence in 7-year-old children: the Yugoslavia Prospective Study.

For a prospective study of lead exposure and early development, we recruited pregnant women from a lead smelter town and from an unexposed town in Yugoslavia and followed their children through 7 years of age. In this paper we consider associations between lifetime lead exposure, estimated by the area under the blood lead (BPb) versus time curve (AUC7), and intelligence, with particular concern for identifying lead's behavioral signature. The Wechsler Intelligence Scales for Children-Version III (WISC-III) was administered to 309 7-year-old children, 261 of whom had complete data on intelligence, blood lead, and relevant sociodemographic covariates (i.e., Home Observation for the Measurement of the Environment (HOME), birth weight, gender, sibship size, and maternal age, ethnicity, intelligence, and education). These showed anticipated associations with 7-year intelligence, explaining 41-4% of the variance in Full Scale, Performance, and Verbal IQ. Before covariate adjustment, AUC7 was unrelated to intelligence; after adjustment, AUC7 explained a significant 2.8%-4.2% of the variance in IQ. After adjustment, a change in lifetime BPb from 10 to 30 micro/dl related to an estimated decrease of 4.3 Full Scale IQ points; estimated decreases for Verbal and Performance IQ were 3.4 and 4.5 points, respectively. AUC7 was significantly and negatively related to three WISC-III factor scores: Freedom from Distractibility, Perceptual Organization, and Verbal Comprehension; the association with Perceptual Organization was the strongest. Consistent with previous studies, the IQ/lead association is small relative to more powerful social factors. Findings offer support for lead's behavioral signature; perceptual-motor skills are significantly more sensitive to lead exposure than are the language-related aspects of intelligence.     

Relationship of clonogenic capacity to plating efficiency and vital dye staining of human periodontal ligament cells: implications for tooth replantation

The survival rate of avulsed permanent teeth following replantation is affected primarily by the duration of the extra-alveolar period and the nature of the storage conditions. These factors are believed to strongly affect the viability of periodontal ligament (PL) cells but in vitro assays of cell viability based on vital dye assays are only weakly correlated with the tooth survival rate after replantation. The aim of the present study was to examine the relative dependence of cell membrane integrity, attachment and clonogenic capacity of human PL cells on the temperature and duration of the extra-alveolar period and the type of storage medium. Twenty-four premolar teeth were extracted for orthodontic reasons from 9 patients 11–18 years of age. Teeth were maintained at 4°C or 23°C for 15, 30, 60 or 120 min in either milk or dry conditions. Cell membrane integrity was determined by BCECF/AM dye inclusion. Plating efficiency was determined by measurement of cell attachment at 3 and 6 h. The clonogenic capacity of progenitor cells was estimated by limiting dilution and colony counts. For all assays teeth stored in milk at 4°C showed the highest percentages of BCECF positive, attached cells with clonogenic capacity. Increased storage time (15–120 min) was associated with a 50% relative reduction of BCECF staining and a 5-fold relative reduction of cell attachment regardless of storage conditions. However, the clonogenic capacity of progenitor cells decreased 25-fold over the same duration of storage. These data demonstrate that in vitro assays of clonogenic capacity are much more sensitive to extra-oral storage time and storage conditions than dye inclusion or cell attachment. We suggest that in comparison with in vitro measures of cell membrane integrity, the clonogenic capacity of PL cells is more closely linked to tooth survival rate, probably reflecting the capacity of PL progenitor cells to recolonize the root surface after replantation.     

Poikilodermatous mycosis fungoides with CD30‐positive large cell transformation successfully treated by brentuximab vedotin

We present a patient with a 33‐year history of poikilodermatous mycosis fungoides (MF) who subsequently developed CD30‐positive large cell transformation. After 6 years of conventional MF treatment, side effects of therapy and/or concomitant diseases prevented the previously applied treatment modalities. The CD30‐directed antibody‐cytotoxic drug conjugate (brentuximab vedotin) was introduced and followed by quick and excellent therapeutic response.     

Transient effect of a short-term educational programme without prophylaxis on control of plaque and gingival inflammation in school children

Abstract The development of chronic inflammatory periodontal diseases is strongly correlated with the growth and maturation of subgingival bacterial colonies. Consequently a major preventive goal should be the control of plaque formation. We conducted a randomized, controlled trial to examine the short-term effect of an intensive instructional program without professional prophylaxis on the gingival health of 240. 11-14 year old school children. Plaque index (P1I), gingival index (GI), bleeding index (BI) and probing pocket depth (PD) were examined 4 × by 1 examiner blinded to the instruction. During the period of instruction, subjects in the experimental groups were involved in a plaque and gingivitis prevention program provided in separate educational sessions. One of the experimental groups (E-l: n=80) was provided with a new toothbrush, toothpaste and instruction while the second experimental group (E-2: n=80) was provided with toothbrush, toothpaste, dental floss and instruction. In the control group (C; n=80) only dental examinations were provided: no preventive program or oral health measures were conducted. Examinations were conducted every 3 months during the instructional period and at 6 months following the completion of the active preventive programme. During the experimental period there was a significant decrease (p<0.001) in the mean P1I. GI and BI of the experimental groups following the program while in controls there was a slight but not significant increase of mean values (p > 0.05). During the preventive program experimental groups exhibited small but not significant (p > 0.05) reductions of PD. Experimental group 1 showed similar PH. GI. BI and PD scores as experimental group 2 during the study. After the instructional program was completed and a period of 6 months had passed, there was a large and significant (p < 0.001) increase of mean P1I. GI and BI scores in both experimental groups back to the baseline levels. We conclude that a short-term preventative program without professional instrumentation induces a transient improvement of gingival health of schoolchildren but only during the instructional period. The maintenance of improved gingival health over longer time periods requires prolonged, repeated instruction by professionals. These measures may be difficult to institute and are of questionable cost-effectivness.     

Relationship between fluoride intake in Serbian children living in two areas with different natural levels of fluorides and occurrence of dental fluorosis

The amount of fluoride present naturally in drinking water is highly variable, being dependent upon the individual geological environment from which the water is obtained. Chronic exposure to exceeding fluoride doses induces set of toxic effects, i.e. fluorosis. The aim of this study was to examine fluoride content in water and in the most frequently used vegetables, potato and bean, grown in two different Serbian regions, i.e. control region (Valjevo) and high naturally occurring fluoride region (Vranjska Banja), and moreover, to correlate estimated daily intake with dental fluorosis occurrence as an adverse effect of fluoride exposure of schoolchildren in Serbia. Study confirmed significant difference in fluoride content in water, potato and bean, consumed by 12-year-old children in two investigated municipalities. Results of the study indicated positive and statistically significant correlation between daily intake of fluoride and dental fluorosis level in the fluorotic municipality of Vranjska Banja (r = 0.61; p = 0.000017). Obtained relationship could be evaluated by means of binary logistic regression analysis, whereas probability for fluorosis occurrence could be predicted using the following equation: fluorosis occurence (%) = (34.852 × C_water − 12.644 × C_potato − 9.362 × C_bean − 7.673) × 100 (Chi-Square (3) = 33.033; p < 0.001).     

Influence of hyperthermal regimes on experimental teratoma development in vitro

We screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model. Rat embryos (three germ layers) were microsurgically isolated and cultivated at the air‐liquid interface. During a two week period, ectodermal, mesodermal and endodermal derivatives developed within trilaminar teratomas. Controls were grown at 37°C. Overall growth was measured, and teratoma survival and differentiation were histologically assessed. Cell proliferation was stereologically quantified by the volume density of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes after plating (CEM43°C 3.75 minutes), diminished cell proliferation (P ? .0001) and enhanced differentiation of both myotubes (P ? .01) and cylindrical epithelium (P ? .05). Hyperthermia of 43°C applied each day for 30 minutes during the first week (CEM43°C 210 minutes) impaired overall growth (P ? .01) and diminished cell proliferation (P ? .0001). Long‐term hyperthermia of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired survival (P ? .005). Long‐term hyperthermia of 40.5°C applied from the second day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival (P ? .0001), overall growth (P ? .01) and cartilage differentiation (P ? .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C 1440 minutes), hyperthermia in the scant serum‐free medium (CEM43°C 630 minutes) or treatment with an anti‐HSP70 antibody before long‐term hyperthermia 40.5°C from the second day (CEM43°C 585 minutes). This in vitro research provided novel insights into the impact of hyperthermia on the development of experimental teratomas from their undifferentiated sources and are thus of potential interest for future therapeutic strategies in corresponding in vivo models.     

Minocycline improves functional outcomes, memory deficits, and histopathology after endovascular perforation-induced subarachnoid hemorrhage in rats

Subarachnoid hemorrhage (SAH) results in significant long-lasting cognitive dysfunction. Therefore, evaluating acute and long-term outcomes after therapeutic intervention is important for clinical translation. The aim of this study was to use minocycline, a known neuroprotectant agent, to evaluate the long-term benefits in terms of neurobehavior and neuropathology after experimental SAH in rats, and to determine which neurobehavioral test would be effective for long-term evaluation. SAH was induced by endovascular perforation in adult male Sprague-Dawley rats (n=118). The animals were treated with intraperitoneal injection of minocycline (45?mg/kg or 135?mg/kg) or vehicle 1?h after SAH induction. In the short-term, animals were euthanized at 24 and 72?h for evaluation of neurobehavior, brain water content, and matrix metalloproteinase (MMP) activity. In the long-term, neurobehavior was evaluated at days 21-28 post-SAH, and histopathological analysis was done at day 28. High-dose but not low-dose minocycline reduced brain water content at 24?h, and therefore only the high-dose regimen was used for further evaluation, which reduced MMP-9 activity at 24?h. Further, high-dose minocycline improved spatial memory and attenuated neuronal loss in the hippocampus and cortex. The rotarod, T-maze, and water maze tests, but not the inclined plane test, detected neurobehavioral deficits in SAH rats at days 21-28. This study demonstrates that minocycline attenuates long-term functional and morphological outcomes after endovascular perforation-induced SAH. Long-term neurobehavioral assessments using the rotarod, T-maze, and water maze tests could be useful to evaluate the efficacy of therapeutic intervention after experimental SAH.