Visual rehabilitation with mini scleral contact lenses in scarred corneas.

PURPOSE: To present a case series of patients with corneal scars who were successfully fitted with mini scleral contact lenses (mSCL). METHODS: Case series study. RESULTS: Six eyes of six patients with corneal scars were fitted with mSCLs. All scars were situated in the visual axis within the scotopic pupillary zone. The sizes of the scars varied, with the smallest being confined to a central corneal area (case 5) and the largest covering the entire visual axis (case 2). In addition to compromising corneal transparency, these scars also induced significant corneal irregularities, especially in cases 1, 3, and 4. The average corrected distance visual acuity (CDVA) with spectacles was 20/80, with a range of 20/200 to 20/40. With the use of mSCLs, CDVA improved to an average of 20/25, ranging from 20/40 to 20/16. The mean visual acuity improvement observed was five optotype lines, with a range of 3 to 7 lines. CONCLUSION: Corneas with scars often exhibit increased higher-order aberrations (HOA), and affected patients not only experience reduced vision but also suffer from seriously reduced optical quality and optical phenomena such as photophobia. Utilizing mSCLs in such individuals can significantly enhance visual acuity and improve optical side effects resulting from corneal opacity and irregularity.

Particle motion measurements near a rocky shore off Cabo Frio Island.

This paper describes the lessons learned from the experiment BIOCOM'19 carried out in January 2019, in a shallow water bay off the island of Cabo Frio (RJ, Brazil). A dual accelerometer vector sensor hydrophone was deployed for two days, near a rocky shore covered with a significant benthic fauna. The results show that the frequency band above approximately 1.5 kHz is mostly associated with invertebrate biological noise and that the acoustic and the particle motion fields have a similar behavior, following the usual dawn-dusk activity pattern, and a coherent directivity content. At low frequencies, below ∼300 Hz, the acoustic pressure and the particle acceleration fields have significantly different spectral content along time. Many of these differences are due to anthropogenic noise sources related with nearby boating activity, while during quiet periods, they may be attributed to the biological activity from the rocky shore.

Evaluation of the toxic and genotoxic potential of acid mine drainage using physicochemical parameters and bioassays.

Carboniferous activity generates acid mine drainage (AMD) which is capable of unleashing toxic effects on the exposed biota. The aim of this study was to evaluate the toxic and genotoxic potential of untreated-AMD and AMD treated with calcinated sediment, using physicochemical parameters and bioassays. Results revealed that untreated-AMD presented low pH values and elevated concentrations of the metals Fe, Al, Mn, Zn and Cu. High acute toxicity was observed in Artemia sp. and Daphnia magna, and sub-chronic toxicity and genotoxicity in Allium cepa L. as well as scission of plasmid DNA exposed to untreated-AMD. Treatment of AMD with calcinated sediment promoted the reduction of acidity and the removal of metals, as well as a reduction in toxic and genotoxic effects. In conclusion, the calcinated sediment can be used as an alternative AMD treatment.

Neural regulation of the stress response: glucocorticoid feedback mechanisms

The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and to restore homeostasis after the immediate challenge has subsided. Release of glucocorticoids is mediated by the hypothalamo-pituitary-adrenal (HPA) axis, driven by a neural signal originating in the paraventricular nucleus (PVN). Stress levels of glucocorticoids bind to glucocorticoid receptors in multiple body compartments, including the brain, and consequently have wide-reaching actions. For this reason, glucocorticoids serve a vital function in negative feedback inhibition of their own secretion. Negative feedback inhibition is mediated by a diverse collection of mechanisms, including fast, non-genomic feedback at the level of the PVN, stress-shut-off at the level of the limbic system, and attenuation of ascending excitatory input through destabilization of mRNAs encoding neuropeptide drivers of the HPA axis. In addition, there is evidence that glucocorticoids participate in stress activation via feed-forward mechanisms at the level of the amygdala. Feedback deficits are associated with numerous disease states, underscoring the necessity for adequate control of glucocorticoid homeostasis. Thus, rather than having a single, defined feedback ‘switch’, control of the stress response requires a wide-reaching feedback ‘network’ that coordinates HPA activity to suit the overall needs of multiple body systems.

Neural regulation of the stress response: glucocorticoid feedback mechanisms.

The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and to restore homeostasis after the immediate challenge has subsided. Release of glucocorticoids is mediated by the hypothalamo-pituitary-adrenal (HPA) axis, driven by a neural signal originating in the paraventricular nucleus (PVN). Stress levels of glucocorticoids bind to glucocorticoid receptors in multiple body compartments, including the brain, and consequently have wide-reaching actions. For this reason, glucocorticoids serve a vital function in negative feedback inhibition of their own secretion. Negative feedback inhibition is mediated by a diverse collection of mechanisms, including fast, non-genomic feedback at the level of the PVN, stress-shut-off at the level of the limbic system, and attenuation of ascending excitatory input through destabilization of mRNAs encoding neuropeptide drivers of the HPA axis. In addition, there is evidence that glucocorticoids participate in stress activation via feed-forward mechanisms at the level of the amygdala. Feedback deficits are associated with numerous disease states, underscoring the necessity for adequate control of glucocorticoid homeostasis. Thus, rather than having a single, defined feedback 'switch', control of the stress response requires a wide-reaching feedback 'network' that coordinates HPA activity to suit the overall needs of multiple body systems.

Coinfection by HTLV-I/II is associated with an increased risk of strongyloidiasis and delay in starting antiretroviral therapy for AIDS patients.

OBJECTIVE: To compare the clinical characteristics and outcomes of HIV-1-HTLV-1 coinfected patients, in Bahia, Brazil. METHODS: Retrospective, comparative study. RESULTS: Among a total of 123 consecutive HIV infected patients, 20 men (20.6%) and 6 women (23.1%) had detectable antibodies against HTLV-I/II. The major risk factor associated with coinfection by HTLV was intravenous drug use (57.7% of coinfected patient versus 9.2% of HTLV seronegative patients, p < 0.0001). Coinfected patients had higher absolute lymphocyte counts (1,921 + 762 versus 1,587 + 951, p = 0.03). Both groups of patients had similar means of CD4+ and CD8+ cell counts. However, among patients with AIDS CD4+ cell counts were significantly higher among those coinfected with HTLV-I/II (292 ± 92 cells/mm³, versus 140 ± 177 cells/mm³, p = 0.36). The frequency and type of opportunistic infections were similar for both groups, but strongyloidiasis and encephalopathy were more frequently diagnosed in coinfected patients (p < 0.05). On the other hand, patients coinfected with HTLV-I/II received significantly less antiretroviral therapy than singly infected by HIV-1. CONCLUSION: Coinfection by HTLV-I/II is associated with an increased risk of strongyloidiasis for HIV patients. Higher CD4 count may lead to underestimation of immunodeficiency, and delay to initiate antiretroviral therapy.

Amygdalar roles during exposure to a live predator and to a predator-associated context.

The amygdala plays a critical role in determining the emotional significance of sensory stimuli and the production of fear-related responses. Large amygdalar lesions have been shown to practically abolish innate defensiveness to a predator; however, it is not clear how the different amygdalar systems participate in the defensive response to a live predator. Our first aim was to provide a comprehensive analysis of the amygdalar activation pattern during exposure to a live cat and to a predator-associated context. Accordingly, exposure to a live predator up-regulated Fos expression in the medial amygdalar nucleus (MEA) and in the lateral and posterior basomedial nuclei, the former responding to predator-related pheromonal information and the latter two nuclei likely to integrate a wider array of predatory sensory information, ranging from olfactory to non-olfactory ones, such as visual and auditory sensory inputs. Next, we tested how the amygdalar nuclei most responsive to predator exposure (i.e. the medial, posterior basomedial and lateral amygdalar nuclei) and the central amygdalar nucleus (CEA) influence both unconditioned and contextual conditioned anti-predatory defensive behavior. Medial amygdalar nucleus lesions practically abolished defensive responses during cat exposure, whereas lesions of the posterior basomedial or lateral amygdalar nuclei reduced freezing and increased risk assessment displays (i.e. crouch sniff and stretch postures), a pattern of responses compatible with decreased defensiveness to predator stimuli. Moreover, the present findings suggest a role for the posterior basomedial and lateral amygdalar nuclei in the conditioning responses to a predator-related context. We have further shown that the CEA does not seem to be involved in either unconditioned or contextual conditioned anti-predatory responses. Overall, the present results help to clarify the amygdalar systems involved in processing predator-related sensory stimuli and how they influence the expression of unconditioned and contextual conditioned anti-predatory responses.

Reference range for T lymphocytes populations in blood donors from two different regions in Brazil

This study defined the normal variation range for different subsets of T-lymphocyte cells count in two different Brazilian regions. We analysed the T-lymphocytes subpopulations (CD3+, CD4+, CD8+) in blood donors of two Brazilian cities, located in North (Belem, capital state of Para, indian background) and Northeast (Salvador, capital state od Bahia, African background) regions of Brazil. Results were compared according to gender, stress level (sleep time lower than 8 hours/day), smoking, and alcohol intake. Lymphocytes subpopulations were measured by flow cytometry. Five hundred twenty-six blood donors from two Brazilians cities participated in the study: 450 samples from Bahia and 76 samples from Pará. Most (60 percent) were men, 59 percent reported alcohol intake, 12 percent were smokers, and 80 percent slept at least 8 h/day. Donors from Bahia presented with significantly higher counts for all parameters, compared with Para. Women had higher lymphocytes levels, in both states, but only CD4+ cells count was significantly higher than men's values. Smokers had higher CD4+ counts, but sleep time had effect on lymphocytes levels only for Para's donors (higher CD3+ and CD4+ counts). That state had also, a higher proportion of donors reporting sleep time <8 h/day. The values for CD3, CD4 and CD8+ cells count were significantly higher in blood donors from Bahia than among those from Pará. Female gender, alcohol intake, stress level, and smoking were associated with higher lymphocyte counts. The use of a single reference range for normal lymphocytes count is not appropriate for a country with such diversity, like Brazil is.

Reference range for T lymphocytes populations in blood donors from two different regions in Brazil.

This study defined the normal variation range for different subsets of T-lymphocyte cells count in two different Brazilian regions. We analysed the T-lymphocytes subpopulations (CD3+, CD4+, CD8+) in blood donors of two Brazilian cities, located in North (Belem, capital state of Para, indian background) and Northeast (Salvador, capital state od Bahia, African background) regions of Brazil. Results were compared according to gender, stress level (sleep time lower than 8 hours/day), smoking, and alcohol intake. Lymphocytes subpopulations were measured by flow cytometry. Five hundred twenty-six blood donors from two Brazilians cities participated in the study: 450 samples from Bahia and 76 samples from Pará. Most (60%) were men, 59% reported alcohol intake, 12% were smokers, and 80% slept at least 8 h/day. Donors from Bahia presented with significantly higher counts for all parameters, compared with Para. Women had higher lymphocytes levels, in both states, but only CD4+ cells count was significantly higher than men's values. Smokers had higher CD4+ counts, but sleep time had effect on lymphocytes levels only for Para's donors (higher CD3+ and CD4+ counts). That state had also, a higher proportion of donors reporting sleep time <8 h/day. The values for CD3, CD4 and CD8+ cells count were significantly higher in blood donors from Bahia than among those from Pará. Female gender, alcohol intake, stress level, and smoking were associated with higher lymphocyte counts. The use of a single reference range for normal lymphocytes count is not appropriate for a country with such diversity, like Brazil is.

Infra-renal abdominal aorta agenesis: a case report with emphasis on MR angiography findings.

The purpose of this study is to report a case of infra-renal aorta agenesis with emphasis on the MR angiography (MRA) findings. A 66-year-old woman presented with urinary complaints. Pelvic and abdominal ultrasound showed hydronephrosis secondary to ureteral lithiasis; the distal portion of the abdominal aorta was not identified. Abdominal CT showed that the infra-renal portion of the abdominal aorta was apparently absent. MRI and MRA demonstrated that, after the origin of the renal arteries, the abdominal aorta spontaneously terminated in two lumbar hypertrophic arteries. In addition, MRA showed a dilated superior mesenteric artery that formed a vascular loop, which continued posterior and inferiorly towards the posterior pelvic region. In this region, it bifurcated and formed internal iliac branches, which were responsible for the arterial supply of the pelvis. In conclusion, MRA allows for precise evaluation of patients with infra-renal abdominal aorta agenesis. Although it is a rare entity, radiologists should be able to recognize it in ultrasound, CT and MRI studies.

Physical environment modulates the behavioral responses induced by chemical stimulation of dorsal periaqueductal gray in mice.

In order to investigate the relationship between behaviors elicited by chemical stimulation of the dorsal periaqueductal gray (dorsal PAG) and spontaneous defensive behaviors to a predator, the excitatory amino acid D,L-homocysteic acid (5 nmol in 0.1 micro l), was infused into the dorsal PAG and behavioral responses of mice were evaluated in two different situations, a rectangular novel chamber or the Mouse Defense Test Battery (MDTB) apparatus. During a 1-min period following drug infusion, more jumps were made in the chamber than in the MDTB runway but running time and distance traveled were significantly higher in the runway. Animals were subsequently tested using the standard MDTB procedure (anti-predator avoidance, chase and defensive threat/attack). No drug effects on these measures were significant. In a further test in the MDTB apparatus, the pathway of the mouse during peak locomotion response was blocked 3 times by the predator stimulus (anesthetized rat) to determine if the mouse would avoid contact. Ninety percent of D,L-homocysteic treated animals made direct contact with the stimulus (rat), indicating that D,L-homocysteic-induced running is not guided by relevant (here, threat) stimuli. These results indicate that running as opposed to jumping is the primary response in mice injected with D,L-homocysteic into the dorsal PAG when the environment enables flight. However, the lack of responsivity to the predator during peak locomotion suggests that D,L-homocysteic-stimulation into the dorsal PAG does not induce normal antipredator flight.

Tamoxifen down-regulates CaMKII messenger RNA levels in normal human breast tissue.

Tamoxifen was proven to reduce the incidence of breast cancer by 49% in women at increased risk of the disease in the Breast Cancer Prevention Trial. In order to identify potential candidates to explain the preventive effect induced by tamoxifen on breast cancer, normal breast tissue obtained from 42 fibroadenoma patients, randomly assigned to receive placebo or tamoxifen, was analyzed by the reverse Northern blot and RT-PCR techniques. The cDNA fragments used on Northern blot membranes were generated by the Human Cancer Genome Project funded by the Ludwig Institute for Cancer Research and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil). Total RNA was obtained from normal breast tissue from patients with clinical, cytological and ultrasound diagnosis of fibroadenoma. After a 50-day treatment with tamoxifen (10 or 20 mg/day) or placebo, normal breast tissue adjacent to the tumor was collected during lumpectomy with local anesthesia. One differentially expressed gene, Calcium/calmodulin-dependent protein kinase II (CaMKII), was found to be down-regulated during TAM treatment. CaMKII is an ubiquitous serine/threonine protein kinase that has been implicated in the diverse effects of hormones utilizing Ca2+ as a second messenger as well as in c-fos activation. These results indicate that the down-regulation of CaMKII induced by TAM might represent alternative or additional mechanisms of the action of this drug on cell cycle control and response to hormones in normal human breast tissue.

Use of the elevated T-maze to study anxiety in mice.

We have recently suggested that the elevated T-maze (ETM) is not a useful test to study different types of anxiety in mice if a procedure similar to that originally validated for rats is employed. The present study investigated whether procedural (five exposures in the enclosed arm instead of three as originally described for rats) and structural (transparent walls instead of opaque walls) changes to the ETM leads to consistent inhibitory avoidance acquisition (IAA) and low escape latencies in mice. Results showed that five exposures to the ETM provoked consistent IAA, an effect that was independent of the ETM used. However, the ETM with transparent walls (ETMt) seemed to be more suitable for the study of conditioned anxiety (i.e. IAA) and unconditioned fear (escape) in mice, since IAA (low baseline latency with a gradual increase over subsequent exposures) and escape (low latency) profiles rendered it sensitive to the effects of anxiolytic and anxiogenic drugs. In addition to evaluation of drug effects on IAA and escape, the number of line crossings in the apparatus were used to control for locomotor changes. Results showed that whereas diazepam (1.0-2.0 mg/kg) and flumazenil (10-30 mg/kg) impaired IAA, FG 7142 (10-30 mg/kg) did not provoke any behavioral change. Significantly, none of these benzodiazepine (BDZ) receptor ligands modified escape latencies. The 5-HT1A partial receptor agonist buspirone (1.0-2.0 mg/kg) and the 5-HT releaser fenfluramine (0.15-0.30 mg/kg) impaired IAA and facilitated escape, while the full 5-HT1A receptor agonist, 8-OH-DPAT (0.05-0.1 mg/kg) and the 5-HT(2B/2C) receptor antagonist, SER 082 (0.5-2.0 mg/kg) failed to modify either response. mCPP (0.5-2.0 mg/kg), a 5-HT(2B/2C) receptor agonist, facilitated IAA but did not alter escape latency. Neither antidepressant utilized in the current study, imipramine (1.0-5.0 mg/kg) and moclobemide (3.0-10 mg/kg) affected IAA or escape performance in mice. The well-known anxiogenic drugs yohimbine (2.0-8.0 mg/kg) and caffeine (10-30 mg/kg) did not selectively affect IAA, although caffeine did impair escape latencies. Present results suggest the ETMt is useful for the study of conditioned anxiety in mice. However, upon proximal threats (e.g. open arm exposure), mice do not exhibit escape behavior as an immediate defensive strategy, suggesting that latency to leave open arm is not a useful parameter to evaluate unconditioned fear in this species.

Association of acanthosis nigricans with race and metabolic disturbances in obese women

Acanthosis nigricans (AN) has been recognized as a marker of insulin resistance and diabetes mellitus. We have compared frequency of race and metabolic disturbances in obese women with several degrees of AN (AN group, N = 190) to a group without AN (non-AN group, N = 61) from a mixed racial population. The groups were similar regarding age and body mass index. All patients (except the diabetic patients) underwent an oral glucose tolerance test (75 g). The racial distribution of this population was 35.1 percent white, 37.8 percent mulatto and 27.1 percent black and the frequency of AN was 62.5, 82.1 and 83.8 percent, respectively, higher in black versus white (P = 0.003) and mulatto versus white (P = 0.002) women. The frequencies of diabetes mellitus and impaired glucose tolerance were 5.8 and 12.6 percent in the AN group and 1.6 and 8.2 percent in the non-AN group, respectively (P>0.05). Fasting glucose, ß cell function determined by the homeostasis model of assessment (HOMA), fasting insulin and insulin area under the curve were similar for the AN and non-AN groups. A higher HOMA insulin resistance was observed in the AN group compared to the non-AN group (P = 0.02) and in the subgroup of highest degree of AN compared to those with other degrees. The mean lipid levels and the frequency of dyslipidemia were similar for the two groups. AN was strongly associated with the black or mulatto rather than the white race, even after taking into account the effect of age, body mass index and HOMA insulin resistance

Association of acanthosis nigricans with race and metabolic disturbances in obese women.

Acanthosis nigricans (AN) has been recognized as a marker of insulin resistance and diabetes mellitus. We have compared frequency of race and metabolic disturbances in obese women with several degrees of AN (AN group, N = 190) to a group without AN (non-AN group, N = 61) from a mixed racial population. The groups were similar regarding age and body mass index. All patients (except the diabetic patients) underwent an oral glucose tolerance test (75 g). The racial distribution of this population was 35.1% white, 37.8% mulatto and 27.1% black and the frequency of AN was 62.5, 82.1 and 83.8%, respectively, higher in black versus white (P = 0.003) and mulatto versus white (P = 0.002) women. The frequencies of diabetes mellitus and impaired glucose tolerance were 5.8 and 12.6% in the AN group and 1.6 and 8.2% in the non-AN group, respectively (P>0.05). Fasting glucose, beta cell function determined by the homeostasis model of assessment (HOMA), fasting insulin and insulin area under the curve were similar for the AN and non-AN groups. A higher HOMA insulin resistance was observed in the AN group compared to the non-AN group (P = 0.02) and in the subgroup of highest degree of AN compared to those with other degrees. The mean lipid levels and the frequency of dyslipidemia were similar for the two groups. AN was strongly associated with the black or mulatto rather than the white race, even after taking into account the effect of age, body mass index and HOMA insulin resistance.

Successful use of a defined antigen/GM-CSF adjuvant vaccine to treat mucosal Leishmaniasis refractory to antimony: A case report.

Immunotherapy has been proposed as a method to treat mucosal leishmaniasis for many years, but the approach has been hampered by poor definition and variability of antigens used, and results have been inconclusive. We report here a case of antimonial-refractory mucosal leishmaniasis in a 45 year old male who was treated with three single injections (one per month) with a cocktail of four Leishmania recombinant antigens selected after documented hypo-responsiveness of the patient to these antigens, plus 50 microg of GM-CSF as vaccine adjuvant. Three months after treatment, all lesions had resolved completely and the patient remains without relapse after two years. Side effects of the treatment included only moderate erythema and induration at the injection site after the second and third injections. We conclude that carefully selected microbial antigens and cytokine adjuvant can be successful as immunotherapy for patients with antimonial-refractory mucosal leishmaniasis.

Co-infection with HTLV-1 is associated with a shorter survival time for HIV-1-infected patients in Bahia, Brazil.

Co-infection with HTLV-1 reaches 20% among patients infected by HIV-1 in Bahia, Brazil. To evaluate its impact on survival, we conducted a retrospective, case-control study involving 198 patients (63 cases). Co-infection was associated with parenteral exposure (P = 0.0001) and female sex (P = 0.02). Co-infected patients had a shorter mean survival (1849 days) than controls (2430 days, P = 0.001), regardless of sex or baseline CD4 cell count. In Bahia, Brazil, co-infection with HIV-1 and HTLV-1 is associated with a shorter survival time.