Identification, characterization and rescue of a novel vasopressin-2 receptor mutation causing nephrogenic diabetes insipidus

Objective  X-linked nephrogenic diabetes insipidus (XNDI), caused by mutations in the V2 vasopressin receptor (V2R), is clinically distinguished from central diabetes insipidus (CDI) by elevated serum vasopressin (AVP) levels and unresponsiveness to 1-desamino-8- d -arginine vasopressin (DDAVP). We report two infants with XNDI, and present the characterization and functional rescue of a novel V2R mutation.
Patients  Two male infants presented with poor growth and hypernatraemia. Both patients had measurable pretreatment serum AVP and polyuria that did not respond to DDAVP, suggesting NDI. However, both also had absent posterior pituitary bright spot on MRI, which is a finding more typical of CDI.
Methods  The AVPR2 gene encoding V2R was sequenced. The identified novel missense mutation was re-created by site-directed mutagenesis and expressed in HEK293 cells. V2R activity was assessed by the ability of transfected cells to produce cAMP in response to stimulation with DDAVP. Membrane localization of V2R was assessed by fluorescence microscopy.
Results  Patient 1 had a deletion of AVPR2 ; patient 2 had the novel mutation L57R. In transiently transfected HEK293 cells, DDAVP induced detectable but severely impaired L57R V2R activity compared to cells expressing wild-type V2R. Fluorescence microscopy showed that myc-tagged wild-type V2R localized to the cell membrane while L57R V2R remained intracellular. A nonpeptide V2R chaperone, SR121463, partially rescued L57R V2R function by allowing it to reach the cell membrane.
Conclusions  L57R V2R has impaired in vitro activity that can be partially improved by treatment with a V2R chaperone. The posterior pituitary hyperintensity may be absent in infants with XNDI.     

Differential Risk of Hypertension Among Lean and Nonlean Rural Subjects in Relation to Decadal Changes in Anthropometry

Objective: Assessing risk of hypertension in relation to decadal changes in anthropometry among cohort of young rural Indian men.

Methods: Subjects (n = 140) were measured in 2005 and 2015 for blood pressure, body mass index (BMI), body fat (BF), waist circumference (WC), waist-to-hip ratio (WHR), and additionally for visceral fat (VF) at follow-up.

Results: Decadal changes showed significant (p < 0.001) increase in mean anthropometric measures and in prevalence of overall obesity (BMI ≥25 kg/m²) from 3.6% to 37.1%; adiposity (BF ≥25%) from 5.1% to 40.9%; and central obesity (WHR ≥0.9) from 0.7% to 24.3%. Prevalence of hypertension increased (20.7% to 27.1%) but was not statistically significant. VF correlated significantly (p < 0.001) with decadal changes (Δ) in BMI, BF, WC, and WHR, and the correlations were stronger (r = 0.90, 0.78, 0.84, and 0.56, respectively) for lean (baseline BMI < median) subjects than nonlean (baseline BMI ≥median) subjects (r = 0.68, 0.40, 0.61, and 0.43, respectively). Risk of hypertension was significant (odds ratio [OR] = 11.0, 95% confidence interval [CI]: 2.8–42.8) for subjects with higher ΔBMI (≥4.7 kg/m²) compared with those with lower ΔBMI (<4.7 kg/m²) among lean but was not significant among nonlean subjects. This was also true for change in other adiposity indicators, indicating greater vulnerability of lean subjects. Further, among lean subjects, ORs reduced considerably after adjusting for VF, whereas among nonlean subjects ORs continued to remain nonsignificant but showing independent significance for VF.

Conclusions: For similar level of change in adiposity indicators, lean subjects were at greater risk of hypertension than nonlean subjects, probably due to higher VF deposition.     

Exploring the Efficiency of Native Tree Species Grown at Mine Tailings for Phytoextraction of Lead and Iron

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Four (4) prominently growing tropical tree species were screened for their tolerance to heavy metals and...     

Demonstration of sweat-based circadian diagnostic capability of SLOCK using electrochemical detection modalities

SLOCK is a sweat-based circadian diagnostic platform used for mapping the user''s chronobiology via cortisol and DHEA. In this work, we have demonstrated the detection capabilities of this sweat-based sensing platform using two electrochemical sensing modalities: Electrochemical Impedance Spectroscopy (EIS) and chronoamperometry. Wicking simulations for vertical versus horizontal flow patterns under potential bias were evaluated using COMSOL Multiphysics®. This work also highlights the biorecognition element characterization using Surface Plasmon Resonance (SPR) and FTIR. Sensor platform was evaluated for biomarker concentrations using doses spanning physiological ranges of 8–141 ng ml⁻¹ and 2–131 ng ml⁻¹ for cortisol and DHEA, respectively. Detailed analysis of impedance data is supported with electrochemical fitting of circuit components related to the biosensing process. Finally, human subject-based studies have been performed to understand the effect of sweating rate with respect to gland density on biosensing. Also, on-body mechanical resiliency studies have been performed to highlight the flexibility of this serpentine electrode-based sensing platform. The platform responds sensitively to the amount of circadian relevant biomarkers in the system with a limit of detection of 0.1 ng ml⁻¹ for both cortisol and DHEA. Thus, the SLOCK platform offers to be an attractive vessel for facilitating the electrochemical detection of circadian relevant biomarkers and for self-monitoring of user''s chronobiology.

SLOCK platform offers to be an attractive vessel for facilitating the electrochemical detection of circadian relevant biomarkers and for self-monitoring of user''s chronobiology.     

Novel method of using angioembolization for treating testicular hemorrhage after blunt trauma

Testicular or scrotal trauma is a rare form of trauma in the United States. Blunt trauma to the testicle can lead to testicular tunica albuginea rupture, testicle contusion, testicle hematoma, testicle torsion and epididymal injury. We report a case of a 48-year-old male patient who presented with right sided scrotal swelling and pain from a motorcycle collision. This turned out to be from a testicular rupture and resulting in a hematoma. The patient''s active bleeding from the right testicular artery was controlled by arterial embolization. Most reported cases of testicular artery bleeds are due to iatrogenic hemorrhage or non-traumatic injuries. Here, we report a rare case of testicular artery bleed due to a blunt trauma from a motorcycle collision. In conclusion, the testicular artery bleed was controlled successfully via testicular arterial embolization, making it a potential option for non-operative management for stable hemorrhage of the testicular artery.     

Frontal subcutaneous lipoma associated with large interhemispheric lipoma and corpus callosum agenesis

Intracranial lipomas are extremely rare fat-containing lesions that comprise 0.1%-0.5% of all primary brain tumors. They are congenital lesions that arise due to persistence and maldifferentiation of the meninx primitive (subarachnoid space precursor). We report a case of a 30-year-old woman who presented with seizures due to an intracranial lipoma and no neurological deficits. CT (computerized tomography) imaging findings demonstrated a large interhemispheric partially calcified lipoma that communicated with a large scalp lipoma and was associated with agenesis of the corpus callosum. Compared to the prior CT imaging, the lipoma increased in size from 3.4 cm to 4.1 cm transversely. A recent CT angiogram done due to suspicion of an aneurysm showed the lipoma now measuring 6 cm by 4.7 cm. Most cases of intracranial lipoma have been reported in the pediatric age group. Here, we report a rare case of interhemispheric intracranial lipoma in the adult age group. This case also demonstrates the importance of imaging modalities for detecting intracranial lipoma without performing invasive brain biopsy.