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Periodontal disease and oral hygiene in a group of blind and sighted Israeli teenagers (14--17 years of age.

The purpose of the present study was to obtain up-to-date information on periodontal disease and oral hygiene status in Israel among 9th to 12th grade non-blind students and among the inmates of six schools for the blind aged 14--17 years. 460 sighted and 434 blind students participated in the study. The examination was for periodontal status and oral hygiene only. Periodontal status was recorded according to Russell's Periodontal Index (PI). Oral hygiene was assessed according to Greene & Vermillion's Simplified Oral Hygiene Index (OHI-S). Mean PI for the non-blind group was found to be 0.23, and for the blind students 0.79. Partially blind students were found to have a lower mean PI value than the totally blind. PI values did not increase significantly with age. Blind students exhibited a fair-to-poor level of oral hygiene (according to Greene & Vermillion's categorization). Relatively healthier levels of oral hygiene were found in the partially blind as compared with the totally blind. Mean OHI-S did not vary with age in either group.

Adolescent

Pathogenesis of mucosal injury in the blind loop syndrome. Brush border enzyme activity and glycoprotein degradation.

The effect of intestinal bacterial over-growth on brush border hydrolases and brush border glycoproteins was studied in nonoperated control rats, control rats with surgically introduced jejunal self-emptying blind loops, and rats with surgically introduced jejunal self-filling blind loops. Data were analyzed from blind loop segments, segments above and below the blind loops, and three corresponding segments in the nonoperated controls. Rats with self-filling blind loops had significantly greater fat excretion than controls and exhibited significantly lower conjugated:free bile salt ratios in all three segments. Maltase, sucrase, and lactase activities were significantly reduced in homogenates and isolated brush borders from the self-filling blind loop, but alkaline phosphatase was not affected. The relative degradation rate of homogenate and brush border glycoproteins was assessed by a double-isotope technique involving the injection of d-[6-(3)H]glucosamine 3 h and d-[U-(14)C]glucosamine 19 h before sacrifice, and recorded as a (3)H:(14)C ratio. The relative degradation rate in both homogenate and brush border fractions was significantly greater in most segments from rats with self-filling blind loops. In the upper and blind loop segments from rats with self-filling blind loops, the (3)H:(14)C ratios were higher in the brush border membrane than in the corresponding homogenates, indicating that the increased rates of degradation primarily involve membrane glycoproteins. Incorporation of d-[6-(3)H]glucosamine by brush border glycoproteins was not reduced in rats with self-filling blind loops, suggesting that glycoprotein synthesis was not affected. Polyacrylamide gel electrophoresis of brush border glycoproteins from the contaminated segments indicated that the large molecular weight glycoproteins, which include many of the surface hydrolases, were degraded most rapidly. Brush border maltase, isolated by immunoprecipitation, had (3)H:(14)C ratios characteristic of the most rapidly degraded glycoproteins. The results indicate that bacteria enhance the destruction of intestinal surface glycoproteins including disaccharidases. Since alkaline phosphatase, a glycoprotein, is not affected, the destruction is selective and presumably involves only the most exposed membrane components.

Animals

Small intestinal mucosal injury in the experimental blind loop syndrome. Light- and electron-microscopic and histochemical studies.

Microscopic (light and electron) and histochemical abnormalities have been demonstrated in the jejunum of rats with the blind loop syndrome. Three groups of animals were studied: normal control animals, and animals with either self-filling (SF) or self-emptying (SE) blind loops. Vitamin B12 malabsorption and bacterial overgrowth occurred only in those animals with SF blind loops. Three jejunal segments were studied: the blind loop segment and the jejunal segments proximal and distal to the blind loop. In the animals with the blind loop syndrome, those with SF blind loops, the most striking findings occurred in the blind loop itself, with similar but less marked changes in the jejunum distal but not proximal to the blind loop segment. Hypertrophy of both crypts and villi was evident with focal abnormalities of villus architecture. Approximately 10 to 20% of the columnar cells in the upper half of the villi were swollen and vesiculated. By electron microscopy microvilli demonstrated a variety of degeneration changes and the glycocalyx and terminal web were disrupted. Mitochondria and endoplasmic reticulum (ER), both smooth and rough, were swollen. Concentric whorls of parallel membranes and long, curvilinear rough ER were present in the cytoplasm. Histochemically, there was loss of enzymatic activity in the epithelial brush border, mitochondria and ER. Inasmuch as bacterial invasion of the jejunal mucosa was not seen, the etiology of these changes is not known but may involve bacterial "toxins" or products of bacterial metabolism. These morphological observations demonstrate that both brush border and intracellular injury occur in the jejunal epithelial cell of rats with the experimental blind loop syndrome.

Animals

Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers.

Maintaining effective blinding is a major methodological challenge in psychedelic research. This study provides a comprehensive evaluation of blinding integrity in 120 healthy volunteers who received either psilocybin, MDMA, or methylphenidate (active placebo) in a double-blind, randomized controlled trial. Using a multi-level assessment incorporating forced-choice substance guesses, certainty ratings, decision factors, and subjective substance effects, the analyses characterize blinding integrity and its relation to the substance experience. Results indicate that overall blinding was insufficient, with psilocybin showing the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern, with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological substance effects. Prior substance experiences did not influence accuracy of forced-choice substance guesses. These findings provide empirical guidance for the design and reporting of blinding procedures in psychedelic trials and underscore the value of systematic, multi-level assessment of blinding integrity.

Humans

Structural and functional alterations in the mucosa of self-filling intestinal blind loops in rats.

1. Self-filling blind loops of jejunum were constructed in three groups of rats; in the first, blind loops were created without further manipulation; in the second the bile was diverted permanently into the lower ileum below the blind loop, whereas in a third neomycin was added to the drinking water throughout the experiment. Two weeks after the creation of the blind loops, they were used for structural and functional studies. 2. Morphometric and microdissection techniques demonstrated that the surface area of the individual villi of the mucosa of 'ordinary' blind loops had increased fourfold in comparison with corresponding control jejunum, whereas the increase was only twofold in rats with bile diversion or in the series treated with neomycin. There were proportional increases in crypt length and mitotoic activity of the crypts in all three series, which suggest that the alterations in the mucosa were due to hyperplasia in both villus and crypt compartments. 3. Sucrase, succinate dehydrogenase, alkaline phosphatase and non-specific esterase activities, determined biochemically or histochemically, were reduced in the mucosae of all blind loops, though the changes were most pronounced in the 'ordinary' blind loops. The accumulation of L-phenylalanine by mucosal slices in vitro was depressed, although the decrease was less marked in the series treated with neomycin. 4. These results suggest that both bacteria and deconjugated bile acids play a role in the development of the hyperplastic changes of the blind-loop mucosa, but that another factor might also be involved: as a possible candidate, stasis of the intestinal contents was considered. 5. To test this hypothesis, loops of rat colon were transposed into the jejunum. Above the transposed loop, the jejunal mucosa developed hyperplasia of both villus and crypt compartments, with a reduction in its ability to accumulate L-phenylalanine. It is argued that these changes, probably caused by stasis of the intestinal contents, are triggered off by the dilatation of the gut, which may also be implicated in the mucosal alterations in blind loops.

Alkaline Phosphatase

Assessment of blinding in pharmacotherapy and noninvasive neuromodulation randomized controlled trials for neuropathic pain in adults.

In randomized controlled trials (RCTs), study participants and research personnel are often blinded to minimize biases related to knowing treatment allocation. To determine if blinding was effective, participants may be asked which treatment they believe they received ("treatment guess"). This descriptive review characterized blinding assessment (BA) reporting in pharmacotherapy and neuromodulation neuropathic pain RCTs. Of 288 papers, 36 (12.5%) reported a BA. One paper reported the results of 2 studies, so in total 37 studies with a BA were assessed. Of these, 19 were crossover, 17 parallel, and 1 partial crossover in design. All 37 studies assessed participant blinding, and 10 also assessed investigator blinding. Approximately 27% included an "unsure" answer option for treatment guess, and 38% asked the reason for the guess. There were no clear patterns in BA reporting across time nor based on treatment type. Seventeen trials provided sufficient data to calculate Bang Blinding Index (BI) to determine blinding success. Participants remained blinded (BI = 0 &#xb1; 0.2) in 10/17 placebo and 10/17 treatment arms, 6 placebo and 5 treatment arms had a BI > 0.2 suggesting possible unblinding, whereas 1 placebo and 2 treatment arms had a BI < -0.2 suggesting misinformed guessing. Overall, we found that BAs are done in a minority of published neuropathic pain trials and with variable methodology. Given the importance of minimizing risk of bias because of treatment unblinding, future studies should consider including BAs, and further consensus building is necessary to determine if and how BAs should be conducted and interpreted in analgesic clinical trials.

Bias

Mental rotation by the blind: does mental rotation depend on visual imagery?

Congentially blind adventitiously blind, and blindfolded sighted adults made same-different judgments of pairs of tactile forms. Two forms were presented in the same orientation, or one form differed from the other by a clockwise rotation of 30 degrees, 60 degrees, 120 degrees, or 150 degrees. Like the reaction times for the sighted and the adventitiously blind, reaction times for the congenitally blind increased as a linear function of angular discrepancy between stimuli, suggesting that the congentially blind, like the sighted and adventitiously blind, mentally rotated one form into congruence with the other to make judging easier. Corroboration of the mental rotation inference came from subjects' introspective reports. Inasmuch as the congenitally blind presumably do not have the ability to visually represent form, the present results suggest that mental rotation does not depend upon visual imagery. Thus, with respect to current speculation as to whether visual imagery is a necessary component of mental rotation, the present findings suggest that it is not.

Adolescent

Diabetic retinopathy. Review of 82 patients presenting with unilateral blindness.

Of the 82 patients who presented to our clinic with unilateral blindness secondary to diabetic retinopathy, 76% had PDR in the blind eye, 4% had non-proliferative retinopathy, and 20% had macular exudates. The second eye, in most instances, had or developed the same pathology as the first eye. Visual prognosis was poor for the 59 patients who had PDR in the second eye; 24 became blind at an average of 15-7 months after presentation. Those patients who were treated seemed to fare better than those not treated. Only three of the fourteen patients who had pituitary ablations became blind, but the average age of this group was, of course, significantly lower than that of the others. Nine of the 22 patients who received photocoagulation became blind in the second eye. Twelve of the 24 patients who received no treatment became blind in the second eye. Visual prognosis for patients with non-proliferative retinopathy was much better; ten patients maintained useful vision for an average of 4 years follow-up. Of the twelve patients with macular exudates in the second eye, three became blind at an average of 34 months after presentation.

Adult

Some causes of blindness seen at Noor Eye Institute, Afghanistan.

This is a survey of the causes of blindness recorded by three students of The City University during a six-week stay at NOOR Eye Institute in Kabul, Afghanistan. The nature of the sample used makes it unsuitable for direct comparison with surveys from other countries. Nevertheless, broad conclusions can be drawn. Severe eye disease is a considerable problem in Afghanistan, in common with other developing countries. The survey included all new patients seen in the outpatient clinic, blind to the extent of being unable to count fingers at more than three metres, in one eye or both. The sample of patients was examined by an ophthalmologist working with our team. A diagnosis was made and various social and demographic questions were asked with the help of an interpreter. In all, 473 patients were examined and included in our survey sample, a very high proportion of the new patients attending the clinic (40.46 per cent). The main causes of blindness were found to be cataract (31.12 per cent), corneal scarring (19.8 per cent), chorioretinal degenerations (6.79 per cent), glaucoma (6.65 per cent) and aphakia (5.52 per cent). Of the major causes of blindness, about forty per cent of the cases were considered remediable, and about thirty per cent could have been prevented. An outstanding difference between the causes of blindness in developed nations and those seen in Afghanistan was the amount of blindness caused by infection, especially in the younger age groups (up to 30 years). Cataract is a major cause of blindness in the older age groups of both societies. People suffering from ocular disease in Afghanistan wait until their sight is badly impaired or lost completely before seeking treatment. This results from a lack of knowledge of what could be done to conserve sight, the irreversible nature of many eye diseases, the distances involved in travelling to the clinic, and even a lack of knowledge of its existence.

Adolescent

Redefining the real problem in psychedelic trials: Why fighting the Lessebo matters more than blinding integrity.

Imperfect blinding is not specific to psychedelic trials. In randomized trials, treatment allocation is frequently correctly guessed, yet blinding integrity is rarely assessed outside of psychedelic research and is generally not considered a barrier in regulatory evaluation. The intense debate in psychedelics may reflect a broader double standard affecting mental health research, when uncertainties arising from imperfect blinding are confounded by those linked to patient-reported outcome measures. Indeed, people living with mental disorders are often viewed as unreliable reporters, despite well-documented limitations of clinician-rated scales and the absence of robust biological markers of symptomatic change. Importantly, it is the maintenance of reasonable doubt of treatment allocation that sustains internal validity and ethical feasibility of placebo-controlled designs, rather than perfect blinding. Concerns about expectancy bias in psychedelic trials are closely tied to blinding debates. When allocation is inferred, expectations may cluster in the arm perceived as active or in stereotyped experiences and influence outcomes differently in active and control arms, leading to a risk of lessebo, a negative placebo effect due to the negative expectation related to receiving a placebo. However, we argue that an underrecognized mechanism of lessebo is disappointment. This risk may reflect insufficient clinical management of disappointment rather than pre-treatment expectation alone. We therefore propose shifting the emphasis from preserving inevitably imperfect blinding towards mitigating disappointment in both arms. Establishing non-stereotyped expectations prior to treatment through structured psychoeducation, strengthened therapeutic alliance, and realistic preparation would help avoid lessebo effects. Such strategies would enhance ethical rigor, interpretability, and the clinical usefulness of psychedelic trials.

Humans

A psychological perspective for double-blind trials.

Blind breaking is likely to occur in a long-term clinical trial involving subjects at risk. Double-blind conditions require subjects to live with ambiguity regarding their health status. It is unrealistic to expect them to tolerate this ambiguity over an extended period of time. A logical step for a subject is to break the blind and surreptitiously seek the best medical care available. Moreover, the staff assigned to monitor protocol adherence may further contribute to blind breaking because of ambiguity regarding their proper clinical role. Several steps are recommended to manage blind breaking within a trial, including improving the quality of medical care, more rigorous screening procedures, and maintaining a clinical environment that promotes accurate disclosure of blind breaking.

Attitude of Health Personnel

Protein digestion and absorption in the blind loop syndrome.

Protein digestion and absorption was studied in rats with 6-week-old surgically constructed self-filling intestinal blind loops and steatorrhea, ie, blind-loop animals and controls were fed a 14C-labeled protein meal containing a nonabsorbable marker, 51CrCl3, and sacrificed 1 or 2 hr later. Intestinal contents were analyzed for 14C, 51Cr, protein, trypsin, and the products of digestion. At 1 hr, 14C absorption was greater in controls, but at 2 hr there was no difference in absorption between the two groups. Marker studies showed that blind-loop filling resulted in a delay of the progression of intestinal contents distally. Intraluminal trypsin and porteolysis were similar in the two groups. Endogenous protein was greater in the blind-loop animals. The early stages of the blind-loop syndrome may be characterized by delayed protein absorption secondary to blind-loop filling, which is compensated for by the distal gut resulting in an absence of overall protein malabsorption.

Animals

Incidence and causes of blindness among the under 5 age group in Malawi.

The expected incidence of blindness among children under 5 years of age in Malawi is 34 cases per 100 000 children. Direct ocular infections were responsible for the blindness in 32% of the cases (bacterial infections 20% and measles 12%). The instillation of traditional medicine in these cases worsened the ocular condition and induced in all of the cases a "hopeless" situation of total melting of the cornea and protrusion of the uvea. Congenital factors (excluding retinoblastomas) were responsible for 30-8% of the blind cases. Among these, 11 cases of congenital cataracts were successfully treated and will not appear as blind in future. A high incidence (9-3%) of cortical blindness was recorded. Trauma was implicated in 5-3%, while retinoblastoma was found in 8%. It is believed that adequate preventive measures should be able to lower the incidence of blindness among this age group to 5 cases instead of 34 per 100 000 children.

Bacterial Infections

An epidemiological study of blindness in an Indian rural community.

A house-to-house survey of blindness in an Indian rural community covering a population of 20 134 in 12 villages revealed a prevalence rate of 35 blind and 144 partially blind persons per 10 000 population. Blindness was significantly associated with the age, sex, marital status, occupation, and socioeconomic status of the respondents. Caratact, glaucoma, smallpox and trachoma were the main causes of blindness. Preventive measures can reduce the toll of blindness in such a community.

Adolescent

Imagery rating and recall in congenitally blind subjects.

Imagery ratings, incidental free recall, and intentional free recall of a group of young congenitally blind adults living in an institute for the blind and of control group were compared. Words to be rated and recalled belonged to three categories: (a) high-imagery words whose referents can be sensorially experienced also by the blind; (b) high-imagery words whose referents cannot be experienced; and (c) low-imagery words. In the control group, both ratings of imagery and recall were affected by the category to which the word belonged. For the blind group the category of the word affected only the ratings of imagery which still assumed a peculiar form since words in category b received extremely low ratings. It is concluded that the blind can evaluate the imagery value of a word, but that their recall is not affected by the level of its imagery value. Therefore, the imagery value really seems to describe, as Paivio asserts, the susceptibility of an item to being coded in a specific visuo-imaginal way, which is more available for sighted than for blind people.

Adolescent

Factors in adjustment to blindness.

We wished to explore the relationship between certain blinding eye diseases, residual vision and psychosocial adjustment, including acceptance of blindness. One hundred and fourteen patients were grouped according to level of vision, age, type of disease, general physical health and duration of blindness. Psychological symptoms were measured by the Minnesota Multiphasic Personality Inventory (M.M.P.I.) and social function by an adaptation to blindness of the Gunzberg Progress Chart of Social Function. Social adjustment was best and psychological morbidity least in those with non-diabetic retinal disorders, those who had the best vision and those who accepted their blindness. Non-acceptance of blindness was associated with the most psychological distress and the lowest scores in social adjustment. People with glaucoma and diabetic retinal disorders seemed more poorly adjusted. An attempt should be made to identify those most prone to maladjustment so as to assist them in rehabilitation.

Adaptation, Psychological

Brush border peptidases and arylamidases in the experimental blind loop syndrome of the rat.

Peptidase and arylamidase activities were assessed in purified brush borders from jejunum of rats with surgically created blind loops. The blind loop segment and the jejunum proximal and distal to the blind loop were studied. Comparable jejunal segments from control rats were also studied. The blind loop syndrome was documented by presence of macrocytic anemia. Enzyme activities were determined on purified brush borders. In rats with the blind loop syndromes enzymatic activities hydrolizing sucrose, L-Leucyl-beta-naphthylamide, L-lysyl-beta-naphthylamide, alpha-L-glutamyl-beta-naphthylamide, L-phenylalanyl-alanine and L-leucyl-glycine were significantly reduced as compared to controls (P less than 0.001). After a short course of antibiotic therapy enzymatic activities returned to normal. Our findings suggest a reversible intestinal mucosa damage in the rat with blind loop syndrome.

Aminopeptidases

Blindness during remission in two patients with acute lymphoblastic leukemia: a possible complication of multimodality therapy.

Two patients with acute lymphoblastic leukemia treated on the same protocol became blind during complete remission. Therapy consisted of systemic combination chemotherapy, prophylactic central nervous system irradiation and monthly intrathecal cytosine arabinoside. Eight months after CNS irradiation visual acuity in both patients began to decrease. Meningeal leukemia in the area of the chiasm was suspected but despite additional radiotherapy, steroids and continued intrathecal therapy, both patients were blind within 6 months. Numerous lumbar punctures were negative for leukemic cells. Extensive investigation, including craniotomy in one case, failed to reveal the cause of blindness. Biopsy of the optic nerve in one case was compatible with radiation toxicity. We postulate that potentiation of radiation toxicity to the optic nerves and chiasm by systemic chemotherapy, intrathecal chemotherapy, or both, may have led to blindness. The patients continue in complete hemotologic and CNS remission 12 and 29 months after becoming blind.

Acute Disease