Visual function improvement using photocromic and selective blue-violet light filtering spectacle lenses in patients affected by retinal diseases.

BACKGROUND: To evaluate functional visual parameters using photocromic and selective blue-violet light filtering spectacle lenses in patients affected by central or peripheral scotoma due to retinal diseases. Sixty patients were enrolled in this study: 30 patients affected by central scotoma, group 1, and 30 affected by peripheral scotoma, group 2. Black on White Best Corrected Visual Acuity (BW-BCVA), White on Black Best Corrected Visual Acuity (WB-BCVA), Mars Contrast Sensitivity (CS) and a Glare Test (GT) were performed to all patients. Test results with blue-violet filter, a short-pass yellow filter and with no filters were compared. RESULTS: All scores from test results increased significantly with blue-violet filters for all patients. The mean BW-BCVA increased from 0.30 ± 0.20 to 0.36 ± 0.21 decimals in group 1 and from 0.44 ± 0.22 to 0.51 ± 0.23 decimals in group 2 (Mean ± SD, p < 0.0001 in both cases). The mean WB-BCVA increased from 0.31 ± 0.19 to 0.38 ± 0.23 decimals in group 1 and from 0.46 ± 0.20 to 0.56 ± 0.22 decimals in group 2 (Mean ± SD, p < 0.0001 in both cases). The letter count for the CS test increased from 26.7 ± 7.9 to 30.06 ± 7.8 in group 1 (Mean ± SD, p = 0.0005) and from 31.5 ± 7.6 to 33.72 ± 7.3 in group 2 (Mean ± SD, p = 0.031). GT was significantly reduced: the letter count increased from 20.93 ± 5.42 to 22.82 ± 4.93 in group 1 (Mean ± SD, p < 0.0001) and from 24.15 ± 5.5 to 25.97 ± 4.7 in group 2 (Mean ± SD, p < 0.0001). Higher scores were recorded with the Blue filter compared to Yellow filter in all tests (p < 0.05). No significant differences in any test results could be detected between the Yellow filter and the No filter condition. CONCLUSIONS: The use of a combination of photocromic lens with a selective blue-violet light filter showed functional benefit in all evaluated patients.

Syndromic and non-syndromic forms of retinitis pigmentosa: a comprehensive Italian clinical and molecular study reveals new mutations.

Mutations in more than 60 different genes have been associated with non-syndromic and syndromic retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies. To increase the understanding of the molecular epidemiology of the disease in Italy, we analyzed 56 patients with syndromic and non-syndromic forms of RP attending the Retinitis Pigmentosa Center of San Paolo Hospital (Milan, Italy). Patients underwent detailed clinical examination. Genomic DNA isolated from peripheral blood samples was screened for mutations in different genes according to RP form by direct sequencing analysis. The impact of novel missense mutations on protein functions was predicted by in silico analysis and protein sequence alignment. Cosegregation analysis was performed between available family members. Forty-one of the 56 probands analyzed had non-syndromic and 15 had syndromic RP forms. Putative disease-causing mutations were identified in 19 of 56 unrelated RP probands. Mutation screening identified a total of 22 different heterozygous variants. Notably, 12 of these putative pathogenic mutations have not been previously reported. New variants were found to be located on the USH2A, RPGR, EYS, and RHO genes. All 3 new variants detected in X-linked RP probands were confirmed in other affected family members. We found a positivity rate of 24.4% and 60% for probands with non-syndromic and syndromic RP, respectively. This is the first report of RPGR X-linked RP proband-ORF15 mutations in Italian patients with X-linked (XL)-RP. In addition, this is the first report of data regarding the association between EYS mutations and non-syndromic RP forms in the Italian population.

Lower lip pits: van der woude or kabuki syndrome?

Kabuki syndrome (KS) is a multiple congenital anomaly/mental retardation syndrome with characteristic facial features. Despite more than 350 documented cases and recent correlation of MLL2 mutations as a genetic cause, its full clinical spectrum is still being defined. This report describes two patients who were initially diagnosed with Van der Woude syndrome (VWS) based on the presence of lower lip pits. However, this finding can occur with KS, albeit infrequently. For patients with lower lip pits, a thorough evaluation should be made to distinguish between VWS and KS, as there are differences in long-term prognosis.

Coconut leaf midrib skewer as a cause for small bowel obstruction and perforation: A case report.

Foreign body ingestion is an infrequent cause of small bowel obstruction and, rarely, perforation. It is a common occurrence among pediatric patients, mentally impaired and the edentulous elderly population majority of which will pass through the gastrointestinal tract uneventfully. The likelihood of complications such as perforation, bleeding or fistula formation increases markedly particularly for sharp, stiff, and elongated objects (i.e. toothpicks, meat bones, pins, and razor blades). Diagnosis can be difficult as frequently patients are incognizant of the nature and time of ingestion. Imaging is commonly non-specific as well. We present an unusual case of a 65-year-old male who had an ileal perforation secondary to a coconut leaf midrib skewer initially presenting as small bowel obstruction. Intraoperatively, adhesions were seen in the ileum with note of the foreign body perforating two bowel loops that was not identified in preoperative imaging. This case highlights the importance of considering atypical causes of small bowel obstruction even in the background of previous surgery. Finally, early recognition, accurate diagnosis, and timely intervention are essential to improve patient outcomes and decrease mortality in such cases.

Metastasizing ameloblastoma of the breast: A case report.

INTRODUCTION: Ameloblastomas are slow growing and locally aggressive odontogenic tumors with a high propensity for recurrence. It frequently arises in the mandible and has been reported to metastasize commonly in the lungs. An updated World Health Organization classification re-categorized metastasizing ameloblastomas under benign tumors. Other rare metastatic sites include the skull, maxilla, kidney, and liver. CASE PRESENTATION: We present a 53-year-old female with a gradually enlarging right breast mass for 2 years. She previously underwent right hemimandibulectomy with clavicular bone grafting 15 years ago for a primary ameloblastoma. Preoperative imaging showed a resectable, heterogenous right breast mass with a biopsy revealing spindle cell neoplasm. She subsequently underwent radical mastectomy with a latissimus dorsi myocutaneous flap as a reconstructive procedure. Histopathologic findings were consistent with a metastasizing ameloblastoma. The patient remains disease-free as of most recent follow-up. DISCUSSION: There are several proposed mechanisms for metastasizing ameloblastomas. Based on the history and location of the tumor, we surmised that tumor seeding from the first surgery done 15 years ago may explain this rare occurrence. Preoperative imaging and biopsy determine resectability and surgical approach. Radical surgery is frequently performed which largely depends on the site of the tumor. Complete primary resection with adequate margins remains to be the treatment of choice to prevent recurrence or metastasis. The role of adjuvant radiotherapy or chemotherapy are still to be established. CONCLUSION: This case highlights the value of history-taking and having a high-index of suspicion for metastasis several years after primary resection of ameloblastomas.

Land use-based landscape planning and restoration in mine closure areas.

Landscape planning and restoration in mine closure areas is not only an inevitable choice to sustain mining areas but also an important path to maximize landscape resources and to improve ecological function in mine closure areas. The analysis of the present mine development shows that many mines are unavoidably facing closures in China. This paper analyzes the periodic impact of mining activities on landscapes and then proposes planning concepts and principles. According to the landscape characteristics in mine closure areas, this paper classifies available landscape resources in mine closure areas into the landscape for restoration, for limited restoration and for protection, and then summarizes directions for their uses. This paper establishes the framework of spatial control planning and design of landscape elements from "macro control, medium allocation and micro optimization" for the purpose of managing and using this kind of special landscape resources. Finally, this paper applies the theories and methods to a case study in Wu'an from two aspects: the construction of a sustainable land-use pattern on a large scale and the optimized allocation of typical mine landscape resources on a small scale.

Prognostic models for diffuse large B-cell lymphoma in the rituximab era: a never-ending story.

BACKGROUND: Improved treatment have modified survival outcome in patients with diffuse large B-cell lymphoma (DLBCL) and altered the importance of previously recognized prognostic markers. DESIGN AND METHODS: To evaluate International Prognostic Index (IPI) score before and after rituximab introduction and to validate the absolute lymphocyte count (ALC)/revised International Prognostic Index (R-IPI) model, we carried out a retrospective analysis on a total of 831 patients with DLBCL. RESULTS: Our results show that IPI lost its discriminating power with the introduction of rituximab. The analysis of our second set allowed us to validate the ALC/R-IPI model. The R-IPI and ALC/R-IPI could still be used for designing clinical trials, but both have difficulty recognizing a high percentage of poor prognosis patients, though it remains an important goal of a good prognostic model considering the modest impact of salvage treatments on survival. CONCLUSIONS: A new model on the basis of significant variables in the rituximab era and built on a large database of patients treated with rituximab is urgently needed. As prognostic models are changing with the efficacy and mechanisms of action of treatment utilized, looking for a new prognostic score is a never-ending story in which researchers are trying to hit a continuously moving target.

Energo- and exergo-technical assessment of ground-source heat pump systems for geothermal energy production from underground mines.

The objective of this study is to perform the energy and exergy analysis of an integrated ground-source heat pump (GSHP) system, along with technical assessment, for geothermal energy production by deployment of Engineering Equation Solver (EES). The system comprises heat pump cycle and ground heat exchanger for extracting geothermal energy from underground mine water. A simultaneous energy and exergy analysis of the system is brought off. These analyses provided persuasive outcomes due to the use of an economic and green source of energy. The energetic coefficient of performance (COP) of the entire system is 2.33 and the exergy efficiency of the system is 28.6%. The exergetic efficiencies of the compressor, ground heat exchanger, evaporator, expansion valve, condenser and fan are computed to be 38%, 42%, 53%, 55%, 60% and 64%, respectively. In the numerical investigation, different alteration such as changing the temperature and pressure of the condenser show promising potential for further application of GSHPs. The outcomes of this research can be used for developing and designing novel coupled heat and power systems.

Wide Excision of a Retroperitoneal Liposarcoma with En Bloc Ureterectomy and Renal Salvage by Autotransplantation.

Liposarcoma is a malignant mesenchymal neoplasm composed of adipose tissue with varying degrees of atypia. These tumors grow slowly and may reach an enormous size particularly if located in the retroperitoneum. We report a 40-year-old male with a 6-month history of gradual abdominal enlargement. Computed tomography (CT) of the abdomen showed a huge retroperitoneal mass with characteristic features consistent with liposarcoma. On laparotomy, the mass was noted to be encasing the right ureter for which a wide excision with en bloc ureterectomy and subsequent renal autotransplantation for organ preservation was done. Post-operative course was uneventful with excellent outcome after 6 months of follow-up. Final histopathologic diagnosis was low-grade, well differentiated liposarcoma, which has favorable prognosis following radical surgery. This was the first report of such a case in the Philippines.

Surface and inner cell behaviour along skeletal muscle cell in vitro differentiation.

During muscle tissue differentiation, in particular in the formation of myotubes from the myoblasts, plasma membrane changes its morpho-functional characteristics. In this study, muscle cell membrane behaviour has been studied along the differentiation of C2C12, a mouse myoblastic adherent cell line. Flat undifferentiated cells, cultured for 3-4 days in the differentiation medium, progressively become thick, long and multinucleated myotubes covered with microvilli. They lose stress fibers and adhesion to the underlying substrate evidentiating an actin redistribution, followed by the spatial organization of thick and thin myofilaments. Sarcomeres and myofibrils occasionally appear, even if a certain percentage of "myosacs" containing randomly oriented filaments can be identified all along the differentiation. M-cadherin, a molecule involved in cell-cell adhesion, also appears in the early differentiation stage, during myoblast fusion. Occasional focal contractions can also be observed in myotubes, which prompt an electrophysiological membrane analysis. When studied by means of patch clamp technique, resting membrane potential appears to undergo a transient depolarization, while input resistance increases until day 5 after differentiation induction, then successively decreases. Capacitance declines until day 5, later appearing enhanced. Moreover, with the induction of differentiation, the pattern of functional voltage-dependent ion channels changes. Therefore, during myogenesis, cell maturation is coupled with changes in cell membrane morphological features and functional characteristics.

Assessment of the mutagenic, antimutagenic and cytotoxic activities of ethanolic extract of araticum (Annona crassiflora Mart. 1841) by micronucleus test in mice.

A typical Brazilian plant, araticum (Annona crassiflora Mart.), is widely used in humans as therapeutic medicine to treat several diseases such as diarrhea, rheumatism and syphilis. It contains acetogenins which present cytotoxic, antitumogenic, and antiparasitic properties. In this study, mutagenic, antimutagenic and cytotoxic effects of araticum leaves ethanolic extract were evaluated by micronucleus test in mice. To evaluate the mutagenic activity, animals were treated with ethanolic extract of araticum (EEA) using 10, 20, 50, 100 and 160 mg.kg(-1). For all doses, micronucleated polychromatic erythrocytes (MNPCE) frequency was evaluated at 24, 48 and 72 hours after treatment. To evaluate the antimutagenic activity, animals were treated with 10, 20, 50 and 100 mg.kg(-1) of EEA and 4 mg.kg(-1) of MMC simultaneously. The frequency of MNPCE was evaluated 36 hours after exposure. Cytotoxicity was evaluated by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). In the mutagenicity assessment, all doses of EEA resulted in no significant increase of MNPCE (P > 0.05), compared to solvent- control group. Regarding administration time, no significant difference among three evaluation periods was observed (P > 0.05). Such results indicate that EEA did not exert mutagenic activity. Cytotoxicity was evident in doses of 50, 100 and 160 mg.kg(-1) at 24 and 48 hours after exposure. Concerning antimutagenicity, except the 10 mg.kg(-1) co-administered with 4 mg/kg of MMC, all doses reduced significantly the frequency of MNPCE compared to the positive control group (P < 0.05). These results, therefore, indicate an antimutagenic activity of the EEA. Cytotoxicity was significantly increased (P < 0.01) at 100 mg.kg(-1) EEA doses co-administered with 4 mg.kg(-1) of MMC.

Structure-function relationship in early diabetic retinopathy: a spatial correlation analysis with OCT and microperimetry.

PurposeTo study the correlation of the local ganglion cell layer-inner plexiform layer (GCL-IPL) thickness with corresponding retinal sensitivity as studied with microperimetry in patients with Type 2 diabetes and no signs of diabetic retinopathy.Patients and methodsWe analyzed 35 healthy subjects (68 eyes) and 26 Type 2 diabetic patients (48 eyes) with no signs of diabetic retinopathy. We tested best corrected visual acuity (BCVA), monocular and binocular constrast sensitivity (CS, Pelli - Robson chart) and retinal sensitivity with microperimetry, and acquired dense macular SD-OCT scans. We then studied the correlation between local GCL-IPL thickness and local sensitivity.ResultsMean BCVA was 1.09 (±1.03) decimals in diabetic subjects and 1.02 (±0.15) decimals in healthy subjects. Only binocular CS was significantly higher in healthy subjects (1.18±0.42 for healthy subjects, 1.62±0.63 for diabetic subjects). In both local and global analysis we observed higher GCL-IPL thickness and higher sensitivity in normal compared with diabetic subjects, but no difference reached significance (p<0.05). Using a mixed multivariate linear model, we found a significant correlation between retinal sensitivity and the correspondent GCL-IPL thickness in diabetic subjects (0.022±0.006 dB/µm, p=0.0007) but not in healthy subjects (-0.002±0.006 dB/µm, p=0.77).Conclusiondespite close similarities between the two groups, we found a significant difference in the structure-function relationship in diabetic subjects without diabetic retinopathy, suggesting that diabetes might act as an additional effect in the normal deterioration of the visual function related to the inner retina.

Neurogenesis in the adult rat dentate gyrus is enhanced by vitamin E deficiency.

Neurogenesis occurs throughout adult life in rat dentate gyrus. Factors and mechanisms of adult neurogenesis regulation are not well known. Vitamin E deficiency has been found to deliver a neurogenetic potential in rat dorsal root ganglia. To determine whether the role of tocopherols in adult neurogenesis may be generalized to the central nervous system, changes in adult rat dentate gyrus neurogenesis were investigated in vitamin E deficiency. Neurogenesis was quantitatively studied by determination of the density of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells and by determination of the total number of cells in the granule cell layer. The BrdU-labeled cells were immunocytochemically characterized by demonstration of neuronal marker calbindin D28K. The following results were found: (1) the volume of the granule layer increased in controls from 1 to 5 months of age, mainly due to cell density decrease; (2) the volume increased by a similar amount in vitamin E-deficient rats, mainly because of an increase in cell number; (3) BrdU-positive cells were more numerous in vitamin E-deficient rats in comparison to age-matched controls; (4) the increase in proliferated cells was located in the hilus and in the plexiform layer. This study confirms that neurogenesis occurs within adult dentate gyrus and demonstrates that this process is enhanced in vitamin E deficiency. This finding indicates that vitamin E may be an exogenous factor regulating adult neurogenesis.

Comparison between the results of an automatic and a visual scoring of sleep EEG recordings.

In this paper, results from the visual scoring of nocturnal polygraphic recordings, carried out by nine different groups of readers from different Italian sleep laboratories, are analyzed; inter-and intragroup variability is shown and statistically discussed. Data are then compared with the results of an automatic scoring of the same recordings, carried out by the Medilog Sleep Stager. The validity of this automatic method of scoring is discussed. Finally, an epoch by epoch analysis is described, with the aim of achieving a more detailed evaluation of the intergroup variability.

Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening.

OBJECTIVE: To evaluate longitudinal growth, pubertal development and final height in patients with congenital hypothyroidism (CH) detected by a neonatal screening programme, and to identify factors potentially affecting growth outcome. PATIENTS: Fifty-five patients (41 females) detected by neonatal screening and followed longitudinally from the time of diagnosis and treatment (25+/-5 days) up to the age of 17+/-0.5 years were evaluated retrospectively. RESULTS: Pubertal development began and progressed normally in both males and females. In boys, a testicular volume of 4 ml was reached at 11.3+/-1.0 years. In girls breast enlargement (B2) occurred at a mean age of 10.3+/-1.2 years and the mean age of menarche was 12.5+/-1.2 years. The onset and the progression of puberty were independent of the aetiology, the severity of CH and the timing of the beginning of treatment. Girls treated with an initial amount of L-thyroxine (L-T4) greater than 8 microg/kg per day showed an earlier onset of puberty (B2 9.4+/-0.9 years; menarche 11.5+/-0.8 years) compared with girls treated with a lower initial dose of L-T4 (B2 10.5+/-1.2 years; menarche 12.6+/-1.2 years; P<0.02). However, both groups attained a similar final height (-0.1+/-1.0 SDS and 0.4+/-1.0 SDS, respectively), which in both cases was above the target height (P=0.03). All the patients in the study attained a mean final height (0.1+/-1.1 SDS) within the normal range for the reference population and above the target height (-0.9+/-0.9 SDS, P<0.0001). No significant relationship was found between final height and severity of CH at diagnosis, initial L-T4 dosage or aetiology of the defect. Patients with ectopic gland, thyroid aplasia or in situ gland attained a similar mean final height (0.1+/-1.1 SDS, 0.5+/-1.0 SDS and -0.5+/-1.0 SDS, respectively), which was in all cases greater than target height (-1.0+/-0.9, -0.6+/-0.8, -0.9+/-0.8 respectively; P<0.05). CONCLUSIONS: Our results suggest that conventional management of children with CH detected by neonatal screening leads to normal sexual development and normal adult height, and that the major factor determining height in these children is familial genetic growth potential.

Changes in opiate activity of rat pituitary following acute administration of neuroleptics.

An increase was found in the opiate activity of pituitary extracts obtained rom rats injected with the neuroleptic drugs trifluoperazine and sulpiride. The increase of opiate activity, measured by bioassay, was particularly evident 2 h after the administration of sulpiride. Dexamethasone completely prevented the neuroleptic-induced effect. Trifluoperazine and sulpiride may have affected dopaminergic mechanisms regulating endorphin storage in the pituitary.

Are there proliferating neuronal precursors in adult rat dorsal root ganglia?

The origin of new neurons in dorsal root ganglia of adult rat was investigated using an experimental model in which postnatal neurogenesis naturally occurring is enhanced and restricted in a brief period of life. Possible mitotic origin of new neurons was investigated by means of 5-bromo-2-deoxyuridine, anti-NF 200 antibody was used to detect if proliferated cells showed a neuronal phenotype. The results suggest that postnatal neurogenesis in dorsal root ganglia could depend only in part on precursor proliferation and that normally new neurons derive from the late differentiation of postmitotic cells.

Alpha-tocopherol controls cell proliferation in the adult rat dentate gyrus.

The effect of alpha-tocopherol on cell proliferation and proliferated cell survival was investigated in the dentate gyrus of adult rats. Adult rats were supplemented with alpha-tocopherol, injected with 5-bromo-2'-deoxyuridine (BrdU), that is incorporated into DNA during the S-phase, and killed at different time after BrdU injection. The number of newborn cells decreased after alpha-tocopherol supplementation, confirming the hypothesis that alpha-tocopherol is able to depress cell proliferation in vivo. Most newborn cells die within few days; more newborn cells survive in alpha-tocopherol-treated rats, suggesting the hypothesis that alpha-tocopherol decreases cell death.

Spatial learning affects immature granule cell survival in adult rat dentate gyrus.

Neurogenesis occurs throughout life in mammalian dentate gyrus. The effect of learning on newborn cell survival was studied in rat. Rats were trained on a hippocampus-dependent spatial learning task by using Morris water maze. Neurogenesis was evaluated by 5-bromo-2'deoxyuridine administered before learning. Several newborn cells expressed the immature neuron marker TOAD-64. The main findings were as follows: (1) the survival of newborn cells was enhanced by learning at early stage of differentiation; (2) the newborn cells saved by learning were mainly located in the rostral part of external blade of granule cell layer and (3) there was a correlation between the actual individual learning and newborn cell survival.

Anti-leishmanial activity of neolignans from Virola species and synthetic analogues.

Surinamensin, a neolignan isolated from Virola surinamensis, 3,4,5-trimethoxy-8-[2',6'-dimethoxy-4'-(E)-propenylphenoxy]-phenylpropane, a neolignan isolated from Virola pavonis, and 25 of its synthetic analogues or correlated substances with ether linkages and their corresponding C-8 sulphur and nitrogen analogues, were tested for activity against Leishmania donovani amastigotes and promastigotes in vitro. Some were active against L. donovani promastigotes at 30 microM but inactive against intracellular amastigotes. The natural neolignan from V. pavonis was active against promastigotes at 100 microM. The highest selective activity was found in those compounds with sulphur bridges. The beta-ketosulfide (3,4-dimethoxy)-8-(4'-methylthiophenoxy)-propiophenone produced 42% inhibition of L. donovani amastigotes in the liver of BALB/c mice at 100 mg/kg given once daily for five consecutive days (P>0.05).