Endemic goitre in India: Prevalence,etiology, attendant disabilities and control measures

Endemic goitre due to iodine deficiency is a health problem that afflicts, with varying degrees, of severity, an estimated 40 million people throughout the subcontinent. In areas where goitre prevalence is high (more than 50%) major attendant disabilities of endemic goitre such as endemic cretinism, deaf—mutism and feeble mindedness are present in about 4% of the population. Iodisation of salt can be an effective prophylactic measure against goitre. Though, a National Goitre Control Programme was launched 2 decades back, only less than 15% of the known goitrous areas have been covered by the programme (1979–80). The major constraints in this regard seem to be inadequate availability of iodised salt. Urgent implementation of iodine prophylaxis is imperative. Also, the benefits of modern technological advancement for early detection and prompt treatment of thyroid related developmental abnormalities of the brain among the new borns in these areas, should be utilised as an interim measure to prevent further such damages.     

Spectrum and clinical profile of post cataract surgery endophthalmitis in north India

PURPOSE: To determine the spectrum, clinical profile and risk factors for poor visual outcome in patients of post cataract surgery endophthalmitis. METHODS: Data from 124 eyes were analysed. Various clinical and microbiological parameters were evaluated and risk factors for unfavourable outcome identified. RESULTS: The mean age of the patients was 59.50 +/- 13.75 years; 60.5% were males. The median surgery-symptom interval was 7 days (mean 15.81 +/- 24.01) and the medium symptom-presentation interval 7.5 days (mean 14.19 +/- 19.13). Corneal infiltrates were seen in 29%, hypopyon in 62 (50%). Smear positivity was 52.5% and culture positivity 38%. Equivocal microbiological positivity was seen in 22 (18%), bacterial 12 (10%), fungal 27 (21.5%), polymicrobial 8 (6.5%) and negative 55 (44%). 20% eyes had total loss of vision at last follow-up. Poor visual acuity at presentation, presence of intraocular lens, shorter surgery-symptom interval, corneal and surgical wound infiltrates, loss of red reflex, microbiological positivity of the vitreous tap and systemic diabetes mellitus were significant risk factors for unfavourable outcome. CONCLUSION: Our data highlights a low culture positivity and a predominance of fungal pathogens as a cause of post cataract surgery endophthalmitis. The visual outcome in these patients is still dismal and better treatment strategies should be evolved keeping in mind the microbiological spectrum. The risk factors identified may be helpful in prognosticating the outcome in such patients.     

Unilateral lateral rectus muscle recession and medial rectus muscle resection with or without advancement for postoperative consecutive exotropia.

PURPOSE: To evaluate the effectiveness of unilateral lateral rectus muscle recession and medial rectus muscle resection with or without advancement in treating postoperative consecutive exotropia. METHODS: We performed a retrospective review on 31 patients with consecutive exotropia who were treated with unilateral lateral rectus muscle recession and medial rectus muscle resection (17 patients) or unilateral lateral rectus muscle recession and medial rectus muscle partial resection combined with advancement (14 patients). All patients had exotropia with a less than 10 prism diopters (PD) distance near-disparity. The characteristics studied before surgery included type of esotropia surgery, detection of amblyopia, presence of an "A" or "V" pattern, dissociated vertical deviation, limitation of adduction, deviation angle measurement, and forced duction testing. Ocular alignment and status of adduction postoperatively at the last follow-up were recorded. RESULTS: Nineteen patients (61.3%) had amblyopia, 17 patients (54.8%) had limitation of adduction, 8 patients (25.8%) had dissociated vertical deviation, and 5 patients (16.1%) had an "A" or "V" pattern. The mean preoperative exodeviation was 47.3 PD. Overall 21 (67.7%) of 31 patients achieved a successful postoperative result (alignment within 10 PD of orthophoria). There was no significant difference in successful alignment in patients treated with unilateral medial rectus muscle resection compared with those treated with unilateral medial rectus muscle partial resection combined with advancement. There was no influence of amblyopia on the result. Twelve (70.6%) of the 17 patients with limited adduction preoperatively showed normalization of adduction postoperatively. CONCLUSIONS: Unilateral lateral rectus muscle recession and medial rectus muscle resection with or without advancement is an effective alternative for treating postoperative consecutive exotropia.     

From the Cover: High frequency of an otherwise rare phenotype in a small and isolated tiger population

Most endangered species exist today in small populations, many of which are isolated. Evolution in such populations is largely governed by genetic drift. Empirical evidence for drift affecting striking phenotypes based on substantial genetic data are rare. Approximately 37% of tigers (Panthera tigris) in the Similipal Tiger Reserve (in eastern India) are pseudomelanistic, characterized by wide, merged stripes. Camera trap data across the tiger range revealed the presence of pseudomelanistic tigers only in Similipal. We investigated the genetic basis for pseudomelanism and examined the role of drift in driving this phenotype''s frequency. Whole-genome data and pedigree-based association analyses from captive tigers revealed that pseudomelanism cosegregates with a conserved and functionally important coding alteration in Transmembrane Aminopeptidase Q (Taqpep), a gene responsible for similar traits in other felid species. Noninvasive sampling of tigers revealed a high frequency of the Taqpep p.H454Y mutation in Similipal (12 individuals, allele frequency = 0.58) and absence from all other tiger populations (395 individuals). Population genetic analyses confirmed few (minimal number) tigers in Similipal, and its genetic isolation, with poor geneflow. Pairwise F_ST (0.33) at the mutation site was high but not an outlier. Similipal tigers had low diversity at 81 single nucleotide polymorphisms (mean heterozygosity = 0.28, SD = 0.27). Simulations were consistent with founding events and drift as possible drivers for the observed stark difference of allele frequency. Our results highlight the role of stochastic processes in the evolution of rare phenotypes. We highlight an unusual evolutionary trajectory in a small and isolated population of an endangered species.

Several recent studies demonstrate that biodiversity is declining globally (1). Such decline includes carnivores (2) and the charismatic tiger (Panthera tigris) in which four subspecies have become extinct in the last century (3). India is home to two-thirds of the world''s tigers, and protection, conservation, and monitoring suggest conservation gains (4). While tigers may have recovered in India overall, some populations remain small and isolated (5). Small and isolated populations have low genetic variation (6) and a high probability of fixation of deleterious alleles (5, 7, 8) because of inbreeding, demographic stochasticity, and random genetic drift, making them prone to extinction (9, 10).Genetic drift can result in the fixation of a deleterious genetic variant over another neutral or even beneficial allele (11). The evidence for drift comes from differences in allele frequencies between replicate populations (12) or changes in allele frequency over time (13) in small populations. Few genetic studies of small, isolated, and endangered populations characterize differences in frequencies of particular variants, especially those associated with visible phenotypes (12–15). In this paper, we identified a genetic variant that causes a phenotypic change in tigers and quantified its frequency in several wild tiger populations, including one that is potentially small and isolated. We further investigated the role of drift in the observed frequency distribution across the tiger range.Diverse pigmentation phenotypes that vary geographically have been observed in many species, including birds, butterflies, mice, cats, horses, and humans (16–25). Unique pigmentation patterns have also been observed [e.g., erythristic leopards (26), the albino fishing cat (27), the white-phased spirit black bear (28), the leucistic Antarctic fur seal (29), and leucistic dolphins (30)]. Together, these observations suggest that alleles responsible for pigmentation phenotypes should vary geographically and be impacted by gene flow and drift. While some studies have attempted to quantify drift using changes in phenotypic frequencies over time (12, 13), we should ideally investigate geographic variation in the frequency of the underlying genetic variant (18). This is often challenging in natural populations because our ability to link genotype to phenotype in non-model systems remains poor (31). Such studies are also plagued with issues of small sample size (29) and poor accessibility to biological material (29) in endangered species.Tigers have a distinctive dark stripe pattern on a light background, which can appear in several color shades—white, golden, and snow white. Segregation of these color variants in captive tiger populations has permitted their genetic and molecular characterization (32, 33). A rare pattern variant, distinguished by pattern elements that are broadened and fused together, has also been observed in natural and captive tiger populations. Such tigers are sometimes called black tigers (34) (Fig. 1A and SI Appendix, Fig. S1), but the melanistic appearance is a consequence of expanded pattern elements rather than a uniformly darkened color, also referred to as pseudomelanism (35) and a term we use to describe the pattern morph henceforth. In the past, pseudomelanistic tigers have been reported from various places (SI Appendix, Table S1, reviewed in ref. 34). More recently, camera trap images from across global range have identified pseudomelanistic tigers from only one population (36), Similipal Tiger Reserve, Odisha (SI Appendix, Fig. S3), a 2,750-km² protected area in eastern India. In addition to this wild population, pseudomelanistic tigers are present in three captive populations in India: Nandankanan Biological Park, Bhubaneswar (NKB), Arignar Anna Zoological Park, Chennai (AAC), and Bhagwan Birsa Biological Park, Ranchi, where they were born in captivity.Open in a separate windowFig. 1.Identifying the genetic basis of pseudomelanism in captive tigers. (A) Normal tiger (Left) versus pseudomelanistic tiger (Right). An increase in the surface area of the coat covered by darker stripes gives the pseudomelanistic tiger a darker, blotchy appearance. (B) The pedigree of the captive tigers sampled for this study. The individual labels shown in red are for the tigers whose genome was sequenced for this study (NKB17 is not shown in the pedigree). The genotype values are indicated for the individuals sampled and successfully genotyped at the mutation site (+/+ for wild-type homozygote, +/m for heterozygote, m/m for mutant homozygote, and x/x for missing genotype). Squares represent males, and circles represent females. Pseudomelanistic phenotype is represented in solid black shapes. The dashed line shows the presence of the same individual at two spots in the pedigree. (C) Schematic diagram and partial alignment of Taqpep protein showing the HEXXHX₁₈E motif (shaded) evolutionarily conserved among vertebrates. The histidine residue at position 454 is substituted by a tyrosine residue in the pseudomelanistic tigers (shown in red). This Taqpep mutational variant is distinct from the Taqpep causal variants implicated for domestic cat Tabby and King cheetah phenotype reported by Kaelin et al. (38)Distinct processes are involved in establishing and implementing mammalian color patterns (37). The implementation process occurs during recurring hair cycles and involves direct engagement with pigment cells to regulate light or dark pigment production, whereas the establishment process coordinates pattern formation during embryogenesis. Taqpep mutations in the domestic cat (Felis catus) and the cheetah (Acinonyx jubatus) (38) alter pattern formation in a manner that is strikingly similar to pseudomelanistic tigers, implicating Taqpep as a strong candidate for pseudomelanism in tigers (39).In this paper, we confirmed a Taqpep missense mutational variant as the genetic basis for a rare pseudomelanistic phenotype in tigers using whole-genome sequence data and known pedigrees of captive tigers that included pseudomelanistic individuals. We confirm the presence of this mutation only in Simlipal, where it occurred at a high frequency in a sample of wild tigers from across their global range. Finally, we used population genetics analyses to investigate whether genetic drift may be responsible for the observed discordant frequency within and outside Similipal by 1) investigating whether Similipal is a small and isolated population and 2) conducting population genetic simulations to explore how founding bottlenecks and genetic drift may change allele frequencies.