Nonsurgical treatment of aggressive periodontitis with photodynamic therapy or systemic antibiotics. Three-month results of a randomized, prospective, controlled clinical study

The aim of this randomized, controlled clinical study was to compare the short-term effects of nonsurgical periodontal therapy with the additional administration of systemic antibiotics (AB) and the same therapy with additional photodynamic therapy (PDT) in the treatment of patients with aggressive periodontitis (AP). Thirty-six patients with AP received full-mouth nonsurgical periodontal treatment (SRP) and were then randomly divided into two groups of 18 subjects each. Group AB received amoxicillin and metronidazole three times a day for 7 days. Group PDT received two applications of PDT on the day of SRP as well as at follow-up after 7 days. The following clinical parameters were measured at baseline and 3 months after therapy: plaque index (PLI), bleeding on probing (BOP), probing depth (PD), gingival recession (GR), and clinical attachment level (CAL). After 3 months, PD was significantly reduced in both groups (from 5.0±0.8 mm to 3.2±0.4 mm with AB, and 5.1±0.5 mm to 4.0±0.8 mm with PDT; both p<0.001), while AB revealed significantly lower values compared to PDT (p = 0.001). In both groups, GR was not significantly changed. CAL was significantly reduced in both groups (PDT: 5.7±0.8 mm to 4.7±1.1 mm; p=0.011; AB: 5.5±1.1 mm to 3.9±1.0 mm; p<0.001) and differed significantly between the groups (p=0.025). The number of residual pockets (PD ≥4 mm) and positive BOP was reduced by AB from 961 to 377, and by PDT from 628 to 394. Pockets with PD ≥7 mm were reduced by AB from 141 to 7, and by PDT from 137 to 61. After 3 months, both treatments led to statistically significant clinical improvements. The systemic administration of antibiotics, however, resulted in significantly higher reduction of PD and a lower number of deep pockets compared to PDT.

Reading on LCD vs e-Ink displays: effects on fatigue and visual strain

Purpose:  Most recently light and mobile reading devices with high display resolutions have become popular and they may open new possibilities for reading applications in education, business and the private sector. The ability to adapt font size may also open new reading opportunities for people with impaired or low vision. Based on their display technology two major groups of reading devices can be distinguished. One type, predominantly found in dedicated e-book readers, uses electronic paper also known as e-Ink. Other devices, mostly multifunction tablet-PCs, are equipped with backlit LCD displays. While it has long been accepted that reading on electronic displays is slow and associated with visual fatigue, this new generation is explicitly promoted for reading. Since research has shown that, compared to reading on electronic displays, reading on paper is faster and requires fewer fixations per line, one would expect differential effects when comparing reading behaviour on e-Ink and LCD. In the present study we therefore compared experimentally how these two display types are suited for reading over an extended period of time. Methods:  Participants read for several hours on either e-Ink or LCD, and different measures of reading behaviour and visual strain were regularly recorded. These dependent measures included subjective (visual) fatigue, a letter search task, reading speed, oculomotor behaviour and the pupillary light reflex. Results:  Results suggested that reading on the two display types is very similar in terms of both subjective and objective measures. Conclusions:  It is not the technology itself, but rather the image quality that seems crucial for reading. Compared to the visual display units used in the previous few decades, these more recent electronic displays allow for good and comfortable reading, even for extended periods of time.

Plasmodium berghei MAPK1 displays differential and dynamic subcellular localizations during liver stage development

Mitogen-activated protein kinases (MAPKs) regulate key signaling events in eukaryotic cells. In the genomes of protozoan Plasmodium parasites, the causative agents of malaria, two genes encoding kinases with significant homology to other eukaryotic MAPKs have been identified (mapk1, mapk2). In this work, we show that both genes are transcribed during Plasmodium berghei liver stage development, and analyze expression and subcellular localization of the PbMAPK1 protein in liver stage parasites. Live cell imaging of transgenic parasites expressing GFP-tagged PbMAPK1 revealed a nuclear localization of PbMAPK1 in the early schizont stage mediated by nuclear localization signals in the C-terminal domain. In contrast, a distinct localization of PbMAPK1 in comma/ring-shaped structures in proximity to the parasite's nuclei and the invaginating parasite membrane was observed during the cytomere stage of parasite development as well as in immature blood stage schizonts. The PbMAPK1 localization was found to be independent of integrity of a motif putatively involved in ATP binding, integrity of the putative activation motif and the presence of a predicted coiled-coil domain in the C-terminal domain. Although PbMAPK1 knock out parasites showed normal liver stage development, the kinase may still fulfill a dual function in both schizogony and merogony of liver stage parasites regulated by its dynamic and stage-dependent subcellular localization.

Loss of Raf-1 kinase inhibitor protein (RKIP) is strongly associated with high-grade tumor budding and correlates with an aggressive phenotype in pancreatic ductal adenocarcinoma (PDAC)

BACKGROUND Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human cancers and is known to inhibit Ras/Raf/MEK/ERK signaling. By suppressing the activation of the NFkB/SNAIL circuit, RKIP can regulate the induction of epithelial-mesenchymal transition (EMT). The aim of this study was to evaluate RKIP expression and to determine its association with clinicopathological features, including EMT in form of tumor budding in pancreatic ductal adenocarcinoma (PDAC). METHODS Staining for RKIP was performed on a multipunch Tissue Microarray (TMA) of 114 well-characterized PDACs with clinico-pathological, follow-up and adjuvant therapy information. RKIP-expression was assessed separately in the main tumor body and in the tumor buds. Another 3 TMAs containing normal pancreatic tissue, precursor lesions (Pancreatic Intraepithelial Neoplasia, PanINs) and matched lymph node metastases were stained in parallel. Cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. RESULTS We found a significant progressive loss of RKIP expression between normal pancreatic ductal epithelia (average: 74%), precursor lesions (PanINs; average: 37%), PDAC (average 20%) and lymph node metastases (average 8%, p<0.0001). RKIP expression was significantly lower in tumor buds (average: 6%) compared to the main tumor body (average 20%; p<0.005). RKIP loss in the tumor body was marginally associated with advanced T-stage (p=0.0599) as well as high-grade peritumoral (p=0.0048) and intratumoral budding (p=0.0373). RKIP loss in the buds showed a clear association with advanced T stage (p=0.0089). CONCLUSIONS The progressive loss of RKIP seems to play a major role in the neoplastic transformation of pancreas, correlates with aggressive features in PDAC and is associated with the presence of EMT in form of tumor budding.

Collagenous Myofibroblastic Tumor of the Mandible: Case Report of a Unique Locally Aggressive Neoplasm Journal Head and Neck Pathology

We report a locally aggressive collagenous myofibroblastic neoplasm of the mandible in an 18-year-old male. Clinically, the lesion presented with rapid growth and irregular mandibular bone destruction. Grossly, the tumor was 10 cm in greatest dimension, light-tan, firm, and involving the posterior one-thirds of the body and inferior half of the left mandibular ramus. Histologically, the lesion was composed of a loose spindle cell proliferation interspersed with periodic dense bands of collagen. The spindle cells reacted positively to smooth muscle actin, calponin, and focally to desmin and were negative for S-100, pan-cytokeratin, CD99, CD34 and caldesmon, supporting myofibroblastic derivation. At our 4 year follow-up, the patient remained free of local recurrence and surgery related complications. The clinicopathologic findings and the differential diagnosis of this lesion is presented and discussed.

Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas.

B-lymphocyte stimulator (BLyS), a relatively recently recognized member of the tumor necrosis factor ligand family (TNF), is a potent cell-survival factor expressed in many hematopoietic cells. BLyS binds to 3 TNF-R receptors, TACI, BCMA, BAFF-R, to regulate B-cell survival, differentiation, and proliferation. The mechanisms involved in BLYS gene expression and regulation are still incompletely understood. In this study, we examined BLYS gene expression, function, and regulation in B-cell non-Hodgkin lymphoma (NHL-B) cells. Our studies indicate that BLyS is constitutively expressed in aggressive NHL-B cells, including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL), playing an important role in the survival and proliferation of malignant B cells. We found that 2 important transcription factors, NF-kappaB and NFAT, are involved in regulating BLyS expression through at least one NF-kappaB and 2 NFAT binding sites in the BLYS promoter. We also provide evidence suggesting that the constitutive activation of NF-kappaB and BLyS in NHL-B cells forms a positive feedback loop associated with lymphoma cell survival and proliferation. Our findings indicate that constitutive NF-kappaB and NFAT activations are crucial transcriptional regulators of the BLyS survival pathway in malignant B cells that could be therapeutic targets in aggressive NHL-B.

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)

Mechanisms of liposomal all-{\it trans\/} retinoic acid and vitamin D3 induced inhibition of cell proliferation and stimulation of apoptosis in aggressive B-cell non-Hodgkin's lymphoma

The Non-Hodgkin's Lymphoma (NHLs) are neoplasms of the immune system. Currently, less than 1% of the etiology of the 22,000 newly diagnosed lymphoma cases in the U.S.A. every year is known. This disease has a significant prevalence and high mortality rate. Cell growth in lymphomas has been shown to be an important parameter in aggressive NHL when establishing prognosis, as well as an integral part in the pathophysiology of the disease process. While many aggressive B cell NHLs respond initially to chemotherapeutic regimens such as CHOP-bleo (adriamycin, vincristine and bleomycin) etc., relapse is common, and the patient is then often refractory to further salvage treatment regimens.^ To assess their potential to inhibit aggressive B cell NHLs and induce apoptosis (also referred to as programmed cell death (PCD)), it was proposed to utilize the following biological agents-liposomal all-trans retinoic acid (L-ATRA) which is a derivative of Vitamin A in liposomes and Vitamin D3. Preliminary evidence indicates that L-ATRA may inhibit cell growth in these cells and may induce PCD as well. Detailed studies were performed to understand the above phenomena by L-ATRA and Vitamin D3 in recently established NHL-B cell lines and primary cell cultures. The gene regulation involved in the case of L-ATRA was also delineated. ^

Behavioral effects of plasma tryptophan depletion in aggressive and nonaggressive men

Serotonin (5-HT) neurotransmission deficits have been implicated in impulsive aggression. A Trp-free beverage of amino acids competitively inhibits Trp uptake into the brain for 5-HT synthesis and also lowers endogenous plasma Trp for several hours. This has worsened mood and/or increased aggressive behavior, especially in hostile persons or those with histories of depression. In 24 community-recruited men (12 each with and without significant aggression histories), aggressive and impulsive behavior in the laboratory was assessed before and after plasma Trp depletion and Trp loading. In the aggression model, subjects were provoked by periodic subtractions of participation earnings, and these subtractions were blamed on a ficitious other participant. Aggression was measured as the responses the subject made to subtract money from his antagonist. Impulsiveness was operationalized as: (1) the choice of smaller reward after a shorter delay over having to wait longer to receive a larger reward, and (2) “false alarm” commission errors in a modified Continuous Performance Task, which represent a failure to inhibit responding to stimuli similar (but not identical) to target stimuli. Finally, plasma cortisol and Trp were measured under each condition immediately following a aggression testing session when subjects were highly provoked. I hypothesized that 5-HT may tonically modulate (inhibit) the hypothalmnic-pituitary-adrenal stress response, such that Trp depletion may enhance the cortisol response to high provocation in aggressive men. ^ Trp depletion had no effect in the laboratory tasks purported to measure impulsive behavior, and failed to cause increases in aggressive behavior under low provocation conditions. Under higher provocation, however, aggressive responses we re elevated under Trp-depleted conditions relative to Trp-loaded conditions in aggressive men, whereas the reverse was true in nonaggressive men. Cortisol levels nonsignificantly paralled the group differences in aggression under Trp-depleted and Trp-loaded conditions. Aggressive men achieved lower plasma Trp levels after Trp loading than did nonaggressive men, possibly due to heavy alcohol use histories. The high post-loading plasma Trp levels in nonaggressive men tended also to correlate with their aggressive responding rates, due perhaps to increases in other psychoactive Trp metabolites. ^

Periodontal pathogens and associated factors in aggressive periodontitis: results 5-17 years after active periodontal therapy

OBJECTIVES To assess the association between presence of periodontal pathogens and recurrence of disease in patients with aggressive periodontitis (AgP) after active periodontal therapy (APT) and further influencing factors. MATERIAL & METHODS Microbiological samples were taken from 73 patients with AgP 5-17 years after APT at 292 sites (deepest site per quadrant). Real-time polymerase chain reactions were used to detect the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. Uni- and multivariate analyses evaluated the associations between pathogens and recurrence of disease, smoking and adjunctive antibiotic therapy. RESULTS At re-examination A. actinomycetemcomitans could be detected in six patients (8.2%), P. gingivalis in 24 (32.9%), T. forsythia in 31 (42.5%) and T. denticola in 35 (48.0%). Increased levels of T. forsythia and T. denticola at re-examination were significantly associated with recurrence of disease in multivariate analyses (OR: 12.72, p < 0.001; OR 5.55, p = 0.002 respectively). Furthermore, high counts of T. denticola were found in patients with increased percentage of sites with clinical attachment levels (CAL) ≥ 6 mm compared to those with low counts (13.8% versus 3.2%, p = 0.005). CONCLUSION In patients with recurrence of disease T. forsythia and T. denticola were detected more frequently and in higher counts. Furthermore, T. denticola was found more frequently in patients with increased CAL.

Six-month results following treatment of aggressive periodontitis with antimicrobial photodynamic therapy or amoxicillin and metronidazole.

OBJECTIVE The use of antibacterial photodynamic therapy (aPDT) additionally to scaling and root planing (SRP) has been shown to positively influence the clinical outcomes. However, at present, it is unknown to what extent aPDT may represent a potential alternative to the use of systemic antibiotics in nonsurgical periodontal therapy in patients with aggressive periodontitis (AP). The aim of this study was to evaluate the outcomes following nonsurgical periodontal therapy and additional use of either aPDT or amoxicillin and metronidazole (AB) in patients with AP. MATERIAL AND METHODS Thirty-six patients with AP displaying at least three sites with pocket depth (PD) ≥6 mm were treated with SRP and either systemic administration of AB for 7 days or with two episodes of aPDT. The following clinical parameters were evaluated at baseline and at 6 months: plaque index (PI), bleeding on probing (BOP), PD, gingival recession (GR) and clinical attachment level (CAL). RESULTS Thirty-five patients have completed the 6-month evaluation. At 6 months, mean PD was statistically significantly reduced in both groups (from 5.0 ± 0.8 to 3.0 ± 0.6 mm with AB and from 5.1 ± 0.5 to 3.9 ± 0.8 mm with aPDT (p < 0.001)). AB yielded statistically significantly higher improvements in the primary outcome parameter PD (p < 0.001) when compared to aPDT. The number of pockets ≥7 mm was reduced from 141 to 3 after AB (p < 0.001) and from 137 to 45 after aPDT (p = 0.03). Both therapies resulted in statistically significant reductions in all parameters compared to baseline. CONCLUSION While both treatments resulted in statistically significant clinical improvements, AB showed statistically significantly higher PD reduction and lower number of pockets ≥7 mm compared to aPDT. CLINICAL RELEVANCE In patients with AP, the two times application of aPDT in conjunction with nonsurgical periodontal therapy cannot be considered an alternative to the systemic use of amoxicillin and metronidazole.

Optimizing stereo-to-multiview conversion for autostereoscopic displays

We present a novel stereo-to-multiview video conversion method for glasses-free multiview displays. Different from previous stereo-to-multiview approaches, our mapping algorithm utilizes the limited depth range of autostereoscopic displays optimally and strives to preserve the scene's artistic composition and perceived depth even under strong depth compression. We first present an investigation of how perceived image quality relates to spatial frequency and disparity. The outcome of this study is utilized in a two-step mapping algorithm, where we (i) compress the scene depth using a non-linear global function to the depth range of an autostereoscopic display and (ii) enhance the depth gradients of salient objects to restore the perceived depth and salient scene structure. Finally, an adapted image domain warping algorithm is proposed to generate the multiview output, which enables overall disparity range extension.