Rubinstein-Taybi syndrome: Clinical profile of 11 patients and review of literature

BACKGROUND:

Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder, characterized by postnatal growth deficiency, typical dysmorphic features, broad thumbs and toes, and mental retardation. Very few cases are reported in literature from developing countries. Diagnosis is often delayed due to non-familiarity with the characteristic features of this syndrome.

AIMS:

To report 11 cases of RSTS and to review the current literature.

SETTINGS AND DESIGN:

Retrospective study conducted in genetic and metabolic unit of a tertiary care teaching hospital in north India over a period of 3½ years.

MATERIALS AND METHODS:

11 patients with diagnosis of RSTS were identified, and their case sheets were reviewed.

RESULTS:

Developmental delay was presenting complaint in 10 patients, and seizure in 1 case. 7 patients had microcephaly (head circumference below −3 SD), and a prominent beaked nose was seen in 9 patients. The intelligence quotient (IQ) varied from 22-62 in 7 patients who had mental retardation. The most notable features in hands were broadness, shortening, and flattening of the distal phalanx of thumbs or great toes. Additionally, we also noted webbing of neck, microphthalmia, and pachygyria (on MRI brain) in 1 patient each.

CONCLUSIONS:

The diagnosis of RSTS is primarily clinical and based on characteristic phenotype that is often combined with a variety of somatic anomalies. An early diagnosis facilitates appropriate genetic counseling and in planning the management.     

Evaluation of productions and economic returns from two brackishwater polyculture systems in tide‐fed ponds

To compare the production and economic performance of two polyculture systems with different species combinations in brackishwater tide‐fed ponds, a 180‐day trial was carried out. In the first combination (T1), mullets (Mugil cephalus, Liza tade and L. parsia at 3 : 1 : 1.3 ratio) and tiger shrimp (Penaeus monodon) and in the second (T2), milkfish (Chanos chanos) and tiger shrimp were stocked keeping the fishes and shrimp at 8000 and 20 000 numbers ha^?1, respectively, in both treatments with duplicate ponds. Since shrimp was an important component of these two systems with open water exchange, the dynamics of heterotrophic bacteria (THB) including Vibrio spp. (TVC) and the occurrence of viral infection agents were studied to understand the disease risks. Among the fishes in T1, M. cephalus attained the highest final weight of 92.29 ± 4.36 g followed by L. tade and L. parsia with 80.40 ± 4.02 and 54.02 ± 2.11 g, respectively. C. chanos in T2 had the highest net weight gain (127.85 g) and daily weight gain (0.71 g day^?1), while M. cephalus in T1 attained the highest specific growth rate (1.60% day^?1). Growth parameters of tiger shrimp were almost similar in both treatments, with no significant differences (P > 0.05). Though total production of fishes and shrimp was lower in T1 (689 kg ha^?1 180 day^?1), it was not significantly different (P > 0.05) from T2 (721 kg ha^?1 180 day^?1). Monthly THB and TVC were not alarming and the absence of viral infections in shrimp indicated no disease risk. Total income from T1 was significantly higher (P < 0.05) than that of T2, but net income and benefit‐cost ratio were insignificantly different between the treatments (P > 0.05). The present findings indicate that upon availability of stocking materials, both polyculture systems would be suitable farming options.     

Altered B cell homeostasis is associated with type I diabetes and carriers of the PTPN22 allelic variant

The PTPN22 genetic variant 1858T, encoding Lyp620W, is associated with multiple autoimmune disorders for which the production of autoantibodies is a common feature, suggesting a loss of B cell tolerance. Lyp620W results in blunted BCR signaling in memory B cells. Because BCR signal strength is tightly coupled to central and peripheral tolerance, we examined whether Lyp620W impacts peripheral B cell homeostasis in healthy individuals heterozygous for the PTPN221858T variant. We found that these subjects display alterations in the composition of the B cell pool that include specific expansion of the transitional and anergic IgD(+)IgM(-)CD27(-) B cell subsets. The PTPN22 1858T variant was further associated with significantly diminished BCR signaling and a resistance to apoptosis in both transitional and naive B cells. Strikingly, parallel changes in both BCR signaling and composition of B cell compartment were observed in type 1 diabetic subjects, irrespective of PTPN22 genotype, revealing a novel immune phenotype and likely shared mechanisms leading to a loss of B cell tolerance. Our combined findings suggest that Lyp620W-mediated effects, due in part to the altered BCR signaling threshold, contribute to breakdown of peripheral tolerance and the entry of autoreactive B cells into the naive B cell compartment.     

Effect of lead, zinc, mercury, and copper with and without estrogen on serum vitellogenin level in Magur fish (Clarias batrachus L.)

Injection(s) of lead, zinc, and mercuric acetate decreased the serum vitellogenin content in Magur fish, while cupric acetate failed to cause any change in the vitellogenin level. Estrogen injections on 7th, 8th and 9th d increased the serum vitellogenin level in normal and copper salt treated fish, but were totally ineffective in altering the reduced vitellogenin content in lead, zinc, and mercury salts treated fish. Vitellogenin level almost restored to normal level at 6 week in lead, zinc, and mercury treated fish, and estrogen injections on 37th, 38th, and 39th d enhanced the serum vitellogenin content in all groups.     

Novel highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulators with pharmacokinetic properties suitable for once-daily oral dosing

Optimization of benzamide PPARδ modulator 1 led to (E)-6-(2-((4-(furan-2-yl)-N-methylbenzamido)methyl)phenoxy)-4-methylhex-4-enoic acid (18), a potent selective PPARδ modulator with significantly improved exposure in multiple species following oral administration.     

Molecular interplay of autophagy and endocytosis in human health and diseases

Autophagy, an evolutionarily conserved process for maintaining the physio‐metabolic equilibrium of cells, shares many common effector proteins with endocytosis. For example, tethering proteins involved in fusion like Ras‐like GTPases (Rabs), soluble N‐ethylmaleimide sensitive factor attachment protein receptors (SNAREs), lysosomal‐associated membrane protein (LAMP), and endosomal sorting complex required for transport (ESCRT) have a dual role in endocytosis and autophagy, and the trafficking routes of these processes converge at lysosomes. These common effectors indicate an association between budding and fusion of membrane‐bound vesicles that may have a substantial role in autophagic lysosome reformation, by sensing cellular stress levels. Therefore, autophagy–endocytosis crosstalk may be significant and implicates a novel endocytic regulatory pathway of autophagy. Moreover, endocytosis has a pivotal role in the intake of signalling molecules, which in turn activates cascades that can result in pathophysiological conditions. This review discusses the basic mechanisms of this crosstalk and its implications in order to identify potential novel therapeutic targets for various human diseases.     

Good Thinking or Gut Feeling? Cognitive Reflection and Intuition in Traders,Bankers and Financial Non-Experts

The current study investigated differences in decision-making style and risk-taking between financial traders, non-trading bank employees, and people not working in finance. Traders scored significantly higher than participants in the other two groups on the cognitive reflection test (CRT) which measures the tendency to inhibit automatic but frequently false responses in reasoning tasks. Scores for traders compared to people outside the banking sector were also higher on a self-rated scale for reflective thinking in decision-making, but there were no differences in self-rated intuitive thinking between groups. Financial risk-taking correlated with cognitive reflection scores and was significantly lower in the non-expert group compared to the other groups working in financial services. Traders in the current study showed no elevated preference to use ‘intuition’ in their decision-making compared to other groups. Overall, these results indicate that compared to non-expert participants financial traders have a higher self-rated tendency for reflective thinking and a greater propensity to inhibit the use of mental shortcuts (heuristics) in decision-making.     

Anthropogenic impact on water quality of Chilika lagoon RAMSAR site: a statistical approach

This paper investigated the spatio-temporal variability of water quality parameters (transparency, salinity, dissolved oxygen, nutrients viz. NH₃-N, NO₂-N, NO₃⁻-N, PO₄³-P, total nitrogen, total phosphorous and chlorophyll-a) in Chilika lagoon during 2001–2003 in order to better understand its ecological characteristics. Marked spatial and seasonal variations were detected with respect to almost all parameters studied. Northern sector of the lagoon is more affected by the anthropogenic stress from the catchments than the southern sector. Addition of nitrogen and phosphorous compounds to the lagoon mainly occurred through the drainage from agricultural lands and river run off during the early months of paddy cultivating seasons. Phytoplankton productivity of the lagoon was nitrogen limited, as suggested by nitrogen to phosphorous ratio. Processes affecting the water quality of the lagoon system included agricultural drainage, sewage intrusion, macrophyte litter fall and exchange of water between lagoon and the sea (Bay of Bengal). Further in depth study pertaining to quantification of exogenous material input and their disposal is recommended to ensure proper management of the lagoon and its resources.