Socio-ecological vulnerability and resilience of mountain communities residing in capital-constrained environments.

The study evaluated perceived reactions and counter-actions of Himalayan communities to climate change. The evaluation was conducted through identification and characterization of 62 socio-environment-specific indicators in three altitude zones (< 1200 m asl (zone A), 1200-1800 m asl (zone B), and > 1800 m asl (zone C)) in Pauri district, Uttarakhand, India, using a bottom-up, indicator-based approach. Indicators with higher significance for the local economy, livelihoods, or conservation were selected and assimilated into dimensions of vulnerability and resilience. Finally, these were integrated into a sustainable livelihood framework in an approach intended to calculate vulnerability and resilience jointly. The results indicated that the vulnerability and resilience of the mountain communities studied varied widely along the altitude gradient, due to variations in socioeconomic profile, livelihood requirements, resource availability, accessibility, and utilization pattern, and climate risk. The overall values for vulnerability (exposure + sensitivity-adaptive capacity) and resilience (exposure + sensitivity-restorative capacity) were, respectively, 0.34 and 0.28 in zone A, 0.54 and 0.37 in zone B, and 0.65 and 0.59 in zone C. There was a significant difference in contribution of indicators to vulnerability and resilience along the altitudinal gradient was recorded. Strategies for dealing with site-specific vulnerability are required and should address bottlenecks in accessibility and availability of food, water, and healthcare; sustainable utilization of forest resources; educational attainment and skill enhancement; and migration. These results extend current knowledge among the research community and policymakers on socio-ecological changes affecting mountain communities. To reduce the policy level gap between bottom-up and top-down approaches, we suggest precautionary and ongoing site-specific traditional practices and modern adaptation practices, leading to effective and efficient handling of local issues in the context of climate change.

Assessment of climate change pattern in the Pauri Garhwal of the Western Himalayan Region: based on climate parameters and perceptions of forest-dependent communities.

This study assessed the climate change in Pauri district, Uttarakhand, India, a region highly vulnerable to climate change with potentially high loss of livelihoods and lives. The scale of change in the district's climate was analyzed using meteorological station data (1901-2000) and grid data (1985-2015). Perceptions of climate change among forest-dependent communities in three altitude zones (< 1200 m asl (zone A); 1200-1800 m asl (zone B), and > 1800 m asl (zone C)) in the study region were surveyed with respect to 14 climate-specific indicators. Annual mean, maximum, and minimum temperature of seasonal data indicated increasing trends except monsoon. Percentage cloud cover showed an increase, of approximately 3%, while diurnal temperature displayed decreasing trends. Rainfall in the district showed a decreasing trend, with more than 50% of years 1985-2015 receiving less rainfall than the annual average. More than 90% of respondents in zones A and B, and around 65-70% respondents in zone C, reported changes in climate parameters. These findings confirm the long-term observable changes in climate in the region and demonstrate the utility of station data, grid data, and surveys of local communities' perceptions when analyzing climate change. The analysis provided important clues about the nature of climate changes in the district. The results can be used to reduce the gap between bottom-up understanding and top-down policies and to formulate precautionary and ongoing site-specific adaptation practices for communities in different altitude zones in the study region, leading to effective and efficient mitigation of climate change impacts.

Ras signaling pathway in the chemopreventive action of different ratios of fish oil and corn oil in experimentally induced colon carcinogenesis.

Dietary factors play a significant role in colon cancer. The essential polyunsaturated fatty acids (PUFAs), n-3 PUFAs, and n-6 PUFAs exert inverse effect on cancer. This study was designed to understand the mechanism of chemopreventive action of different ratios of fish oil (FO) and corn oil (CO) in colon carcinoma. Wistar rats were divided into 3 groups: Group 1 received purified diet whereas Groups 2 and 3 received modified diet with FO:CO (1:1) and FO:CO (2.5:1), respectively. The groups were further subdivided into controls receiving ethylenediamine-tetra acetic-acid and treated groups received dimethylhydrazine-dihydrochloride (DMH)/wk for 4 wk. Animals sacrificed 48 h after last injection constituted initiation phase and that sacrificed after 16 wk constituted post-initiation phase. Differential effect of different ratios of FO and CO was analyzed in isolated colonocytes. In both phases, DMH treatment showed an increase in pan Ras, Raf, MEK1/2, extracellular signal regulated kinase (Erk)1/2, and c-fos levels. Akt levels were increased in post-initiation phase only. Treatment with FO + CO (1:1) + DMH decreased pan Ras, MEK1/2 and Erk1/2 levels in post-initiation phase whereas Raf and c-fos were decreased in both phases. Treatment with FO + CO (2.5:1) + DMH decreased Ras, Raf, MEK1/2, Erk1/2, and c-fos levels in both phases. Akt was decreased in post-initiation phase only. The chemo-preventive action of FO and CO may be mediated by time- and dose-dependent effect.

Endodontic management of mandibular central incisor fused to a supernumerary tooth associated with a talon cusp: a case report.

AIM: To report the successful non-surgical endodontic management of a mandibular central incisor fused to a supernumerary tooth associated with a talon cusp. SUMMARY: Fusion and gemination are developmental anomalies of teeth that may require endodontic treatment. In this article, a case of successful endodontic management of a permanent mandibular right central incisor fused to its supernumerary counterpart associated with a talon cusp is reported. The incidence of fusion in mandibular anteriors is rare. A search of the literature failed to reveal any reports on the fusion of a permanent mandibular central incisor with its supernumerary counterpart associated with a talon cusp. Successful non-surgical endodontic management of a case is reported. KEY LEARNING POINTS: • Fused and geminated teeth requiring endodontic treatment present diagnostic and technical challenges. • An exact differentiation between fusion and gemination may not be critically important for treatment. • The use of an operating microscope for detection of additional root canal orifices in complicated cases is recommended.

Alkaptonuria and intramedullary calcification.

Alkaptonuria is a rare disorder of metabolism caused by deficiency of homogentisic acid oxidase enzyme and characterized by triad of homogentisic aciduria (dark urine), relentlessly progressive arthritis and ochronosis. We have documented a case with typical features of alkaptonuria along with intramedullary calcification which has not been reported in the literature before.

Different transitions of multifocal electroretinogram recordings between patients with age-related macular degeneration and polypoidal choroidal vasculopathy after photodynamic therapy.

AIM: To compare and evaluate the transitions in retinal function after photodynamic therapy (PDT) between age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) using multifocal electroretinograms (mfERGs). METHODS: 10 eyes with choroidal neovascularisation (CNV) secondary to AMD and 11 eyes with CNV secondary to PCV were included in the study. mfERGs were recorded before PDT, and 1 week and 3 months after PDT. mfERG recordings were acquired by a Veris system (V.3.1.3) using a 103 hexagon stimulus. The first-order kernel was used to calculate amplitudes and latencies. Mean amplitudes and latencies from two central rings rated 0-4 degrees of visual angle were analysed and compared with each disease. RESULTS: In AMD, the mean first negative peak (N1) amplitudes tended to decrease, and the mean first positive peak (N1P1) amplitudes reduced to significant levels (p = 0.047) 1 week after PDT. 3 months after PDT, there were no significant differences in the mean N1 and N1P1 amplitudes compared with pre-PDT values. In PCV, there were no significant changes in the mean N1 and N1P1 amplitudes 1 week after treatment. However, 3 months after PDT, mean amplitudes showed significant increases in N1 (p = 0.008) and N1P1 (p = 0.006) amplitudes compared with pre-PDT values. CONCLUSIONS: mfERG recording transitions are different between patients with AMD and those with PCV. In patients with AMD, these results may show transient impairments in retinal function 1 week after PDT, but in those with PCV, the efficacy of PDT is superior to the impairment after PDT.

Epidemiology of a new focus of localized cutaneous leishmaniasis in Himachal Pradesh.

A new focus of localised cutaneous leishmaniasis has emerged along the Satluj River valley in the mountainous region of north west Himachal Pradesh. The main endemic region extends from Pooh subdivision of Kinnaur district to Kumarsain subdivision of Shimla district with adjoining Nirmand subdivision of Kullu District comprising 86 villages. The climate of the affected areas varies from temperate to subtropical. A total of 285 cases were recorded from 1988 to January, 2005. The age of these patients varied from 10 months to 75 years, with 63 children (<12Years), and a male to female ratio of 1: 0.9. The duration of disease was 15 days to 48 months with majority (85%) presenting between 1-6 months. The number of lesions varied from 1-8, and were mostly seen on exposed parts of the body. Morphologically, lesions were asymptomatic, dry, nodular or crusted nodulo-ulcerative plaques. Tissue smear positivity for amastigotes was 43%. The characterization of 14 strains of these Leishmania revealed presence of both Leishmania tropica (n=3) and Leishmania donovani (n=11). Identification of the 42 sandflies collected from the peridomestic environment of the patients, revealed Phlebotomus longiductus - 29, P. major 8, P. kandelaki 2, while 2 remained unidentified. The patients were treated with intralesional sodium stibogluconate and majority showed excellent response.

N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine reduces intracellular calcium response to noradrenaline in rat visual cortex.

Using the fluorescent indicator Fura-2, we investigated the effects of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin, on intracellular calcium responses to noradrenaline, N-methyl-D-aspartate, and carbamylcholine chloride in brain slices of the rat visual cortex. Noradrenergic depletion in the visual cortex of young rats was induced by DSP-4, and its selectivity was confirmed by two different methods, i.e., immunostaining with anti-dopamine-beta-hydroxylase antibody and biochemical analysis by high-performance liquid chromatography. The treatment with DSP-4 (25 mg/kg i.p., x2) caused disruption of noradrenergic fibers throughout all cortical layers, and reduced the content of noradrenaline to 6.4% of that in the normal control. In the normal cortex, bath-applied noradrenaline (100 microM) increased the intracellular calcium to 123% of the control in terms of the F(340)/F(380) ratio of Fura-2 fluorescence. Quantitative analysis of the F(340)/F(380) ratio was performed in layers II to IV, since the increase was mainly observed in these layers. The intracellular calcium response to noradrenaline was significantly (P<0.0001) reduced in the DSP-4-treated animals to 63.2% of that in the normal control. The response to N-methyl-D-aspartate (100 microM) was also reduced, whereas the response to carbamylcholine chloride, a muscarinic cholinergic agonist (100 microM), was not affected by the DSP-4 treatment. From these findings we suggest that noradrenergic denervation by DSP-4 reduces the intracellular calcium response to noradrenaline through changes in the intracellular signal transduction.

Effects of subretinal and systemic osmolality on the rate of subretinal fluid resorption.

Small norhegmatogenous retinal detachments (blebs) were made in Dutch rabbit eyes by injecting solution into the subretinal space. There was no difference in resorption time between blebs made with isotonic, hypertonic or hypotonic sodium chloride. However, blebs made with sucrose solution took longer to resorb than those made with Hanks' solution, regardless of whether the sucrose was hypotonic or hypertonic. Intravenous injection of hyperosmotic solution (mannitol) accelerated the resorption of Hanks'-filled blebs but the injection of hypoosmotic solution (water) had no clear effect. The authors conclude that osmotic differences between the subretinal space, and the vitreous and/or choroid, are rapidly equilibrated by the surrounding tissues; but the rate of bleb resorption will be affected by the size and membrane permeability of the molecules within the subretinal space. The effects of increased serum osmolality may involve not only osmotic pressure but an opening of the tight junctions of the RPE.

Ion movement in and out of the vitreous space after vitrectomy. An experimental study on the in vivo eyecup preparation of rabbits.

Osmotic pressure and ion movements in and out of the vitreous space after open-sky vitrectomy were studied in the in vivo eyecup of rabbits. The osmotic pressure of several hypo-osmotic solutions rose over a period of time by the penetration of ions from the surrounding tissue; increases in the concentration of sodium, chloride, potassium, and calcium were documented. Appearance and disappearance of ions were independent of the total osmolarity and depended on the concentration gradient for each ion.

Quantitative estimation of metabolic transport of subretinal fluid.

A new technique to measure the ongoing rate of subretinal fluid resorption inside the living eye is described. Experimental non-rhegmatogenous detachments (blebs) were made in the posterior pole of rabbit eyes by injecting fluid directly into the subretinal space, and the height of these blebs was measured with a YAG laser focusing system utilizing dual He-Ne beams. The resorption rate for Hanks' balanced salt solution was relatively constant during the initial 2.5 hr, and averaged 0.12 +/- 0.04 microliter/mm2/hr. The resorption rate for blebs made with non-ionic solution (isotonic sucrose) was only 0.03 microliter/mm2/hr. The resorption rate for blebs made with Hanks' solution plus 1 mM DNP was 0.04 microliter/mm2/hr. These data support the concept that subretinal fluid is resorbed primarily across the retinal pigment epithelium, and suggests that 70% of this absorption is dependent upon active ionic transport. The remaining 30% is probably driven by the higher oncotic pressure of the choroid.

Mechanisms of subretinal fluid resorption in the cat eye.

Small, non-rhegmatogenous retinal detachments (blebs) were made in cat eyes by injecting fluid into the subretinal space, and the time course of fluid resorption was monitored. Blebs made with Hanks' solution over the pigmented RPE resorbed 22% faster than those over the tapetum. Blebs made with a non-ionic solution (isotonic sucrose) took 43% longer to resorb than those made with Hanks' solution, and blebs containing 3 X 10(-3) M sodium cyanide took 32% longer than controls. These results suggest that active ionic transport is involved in the absorption of subretinal fluid in the cat, as it is in the rabbit. Oncotic pressure in the choroid may also contribute to resorption, because blebs made with autologous serum took roughly 3 times longer to resorb than those made with non-proteinaceous Hanks' solution. The retinal vascular system does not appear to contribute, since the resorption time was similar for Hanks' blebs made under normal retina and those made under ischemic retina (produced by occluding retinal branch arteries with argon laser photocoagulation or endodiathermy).

Comparative study of vitreous oxygen tension in human and rabbit eyes.

For the first time, vitreous oxygen tension in the human vitreous body was measured using a polarographic oxygen electrode during vitreous surgery. The same method was used in a rabbit experimental model. In the human eye, the mean oxygen tensions of the anterior peripheral vitreous body, central vitreous body and posterior vitreous body were 16.7 +/- 3.7 mm Hg (mean +/- 1 SD), 15.9 +/- 2.8 mmHg and 19.9 +/- 4.8 mm Hg, respectively, while the preretinal oxygen tension of the detached retina was 30.0 +/- 4.8 mm Hg. In the rabbit eye, the mean oxygen tensions of the anterior peripheral vitreous body, central vitreous body and posterior vitreous body were 13.9 +/- 4.3 mm Hg, 16.0 +/- 3.5 mm Hg and 22.5 +/- 2.1 mm Hg, respectively. The preretinal oxygen tension of the attached retina in the rabbit eye was 39.5 +/- 3.4 mm Hg, while that of the detached retina decreased to 4.3 mm Hg. When comparing human with rabbit eyes, it appears that the vitreous oxygen tensions are similar, except over the detached retina, even though the ocular circulation differs. We believe that human retinal vasculature plays an important role in perfusing the detached retina with relatively high levels of oxygen.

The resorption of subretinal fluid after diffuse damage to the retinal pigment epithelium.

We studied the role of the retinal pigment epithelium (RPE) in the resorption of different subretinal fluids from under small experimental retinal detachments (blebs) in the rabbit. Damaging the RPE with sodium iodate caused the resorption time, for blebs made with an ionic solution (Hanks'), to decrease from 2-6 hours to only about 30 minutes. Blebs made with sucrose also absorbed much more quickly after iodate. However, blebs made with autologous serum resorbed no faster after iodate. We conclude that iodate destroys the membrane barrier properties of the RPE, allowing subretinal fluid to cross freely according to oncotic pressure. We postulate that in the normal eye, where osmotic fluid movement is low because of the high resistance barrier, the RPE must transport fluid actively to keep the subretinal space dehydrated.

Effects of intraocular pressure and other factors on subretinal fluid resorption.

We observed the effects of intraocular pressure (IOP), vitreous pressure and gravity on the resorption of small retinal detachments (blebs) made with Hanks' solution or autologous serum. Raising the IOP decreased the absorption time moderately and lowering the IOP increased it. These effects were greater when the RPE had been damaged by sodium iodate or laser burns, but we conclude that IOP makes only a small, limited contribution to normal subretinal fluid absorption. Neither liquefaction of the vitreous nor retinal weight had a significant influence on fluid absorption.

Acute changes in RPE apical morphology after retinal detachment in rabbit. A SEM study.

The morphology of the apical surface of rabbit retinal pigment epithelium was studied by scanning electron microscopy from the first minute to several hours after making small nonrhegmatogenous retinal detachments (blebs). From 0 to 5 min, there were only slight changes in the homogeneous, dense mat of filamentous microvilli. From 5 to 30 min, filamentous microvilli retracted exposing larger processes. From 30 to 60 min blunt processes became completely exposed and sheet-like processes disappeared. At about 60 min, cone sheaths were no longer identifiable in most specimens. Between 60 min and the time of retinal reapposition (several hours), the apical surface became highly rounded. Colchicine and cytochalasin-D had no effect on the time required for fluid resorption, but colchicine greatly accelerated and enhanced cell rounding, while cytochalasin-D produced prominent apical tufts.

Lowering the calcium concentration in the subretinal space in vivo loosens retinal adhesion.

Retinal adhesiveness in vitro is reduced by lowering the external calcium (Ca2+) concentration. The effects of lowering subretinal Ca2+ concentration in living rabbit eyes was investigated by making experimental retinal detachments (blebs) filled with Ca(2+)-free disodium edetate solution. Unlike blebs made with Hanks' solution, these low-Ca2+ blebs enlarged progressively after they were formed, and they were surrounded by a wide whitish halo. This halo region had weak adhesion (shown by the rapid spread of fluorescein solution into the halo and by the measurement of local adhesiveness after enucleation). The retinal pigment epithelial microvilli in the halo appeared stretched toward the center of the blebs as if there had been retinal traction or movement. Measurements of retinal adhesiveness in vivo showed it to be decreased to about 30% of normal by use of this solution.

Measurement of retinal adhesive force in the in vivo rabbit eye.

A new method to evaluate the retinal adhesive force, which was defined as the force needed to achieve adhesive failure per unit length, in the in vivo rabbit eye was tested. A small dome-shaped retinal detachment (bleb) was made in the posterior pole by injecting balanced salt solution into the subretinal space. A separate measuring micropipette with a tip diameter of 5 microns was inserted into the subretinal space. The subretinal pressure was measured directly with the resistance servonulling method as the solution was injected repeatedly into the subretinal space. According to Laplace's law, the retinal adhesive force per unit length in normal Dutch rabbits was calculated to be (1.8 +/- 0.2) X 10(2) dyn/cm (n = 87). This value was about five times larger than that reported previously with in vitro peeling methods. The new method will resolve several problems encountered in the previous methods and will allow for the measurement of the retinal adhesive force more physiologically and precisely.

Retinal damage by air infusion during vitrectomy in rabbit eyes.

PURPOSE: Visual field defects after vitrectomy can be seen after any surgery involving fluid-air exchange. To elucidate the effect during surgery of the infused air on the retina, the present study investigated the changes in the morphology of the rabbit retina induced by air infusion and the changes resulting from varying amounts of infused air pressure. METHODS: Eighteen eyes of 18 rabbits were used. A standard three-port vitrectomy with artificial posterior vitreous detachment followed by fluid-air exchange was performed in 12 eyes. During the fluid-air exchange, humidified air was infused with an air pressure of 25 or 40 mm Hg for 30 seconds. As a control, vitrectomy without fluid-air exchange was performed in six eyes. The eyes were enucleated and fixed immediately. Specimens were processed and examined by light and scanning electron microscopy (SEM). RESULTS: With SEM, sharply demarcated retinal lesions were observed at the opposite side from the infusion cannula in all eyes in which a fluid-air exchange was performed. At the lesion, the internal limiting membrane was often detached, and the underlying nerve fiber layer was exposed. Light microscopy revealed that the inner retina was most affected, with concomitant swelling of the inner plexiform layer and the inner granular layer. In addition, the retina was often focally detached with adhesion of some retinal pigment epithelial cells to the photoreceptor cells. Increased infused air pressure was accompanied by a significant increase in the area of retinal damage. In contrast, no morphologic change was observed in the control eyes. CONCLUSIONS: Air infusion during vitrectomy can cause mechanical retinal damage in the rabbit retina. The mechanical damage may result in a visual field defect after vitrectomy.

Lecithin-bound superoxide dismutase in the prevention of neutrophil-induced damage of corneal tissue.

PURPOSE: To evaluate the effects of a lipophilic analog of superoxide dismutase (SOD) in the prevention of polymorphonuclear leukocyte (PMN)-induced damage to corneal epithelial cells in vitro and in bacterial corneal ulcers in vivo. METHODS: Immortalized human corneal epithelial cells (T-HCEC) were cocultured with human PMNs activated with N-formyl-methionyl-leucyl-phenylalanine for 18 hours, after which lactate dehydrogenase (LDH) activity of the supernatant was measured as a marker of cellular damage. The inhibitory effects of lecithin-bound SOD (PC-SOD) and unmodified SOD, as well as PMNs pretreated with anti-CD 18 monoclonal antibody, were compared with untreated control. The retention of each drug on the ocular surface of healthy volunteers was measured by flow cytometry using brush cytology samples. The protective effects of a 0.1% solution of PC-SOD on Pseudomonas aeruginosa corneal infection in guinea pigs were assessed by inflammatory grading scores and histology. RESULTS: Both PC-SOD and SOD effectively suppressed PMN-induced LDH release in T-HCEC in a dose-dependent manner. LDH release was also attenuated when PMNs were pretreated with anti-CD 18 antibodies, suggesting that adhesion molecules were involved in the process. Brush cytology of conjunctival samples showed that PC-SOD was retained longer on the ocular surface compared with unmodified SOD. PC-SOD significantly prevented excessive tissue damage by infiltrating PMNs in P. aeruginosa corneal infection, whereas in control eyes, perforation of the cornea occurred by 6 days. CONCLUSIONS: PC-SOD was effective in attenuating PMN-related tissue damage to corneal tissue both in vitro and in P. aeruginosa infection in guinea pigs.