Retinopathy of prematurity—promising newer modalities of treatment

Retinopathy of prematurity (ROP) is a disorder of neonatal retinal vascularization. The incidence is increasing in developing countries like India in view of the rising numbers of preterm deliveries and improved neonatal care. Traditional modalities of treatment included cryotherapy and laser therapy, which were laborious and required special training. Hence, research is on way to find novel treatment modalities directed at various levels of pathogenesis for this blinding disease. We reviewed the published and unpublished literature on newer methods of ROP management. The pathogenesis of ROP has been studied with respect to the mediators of angiogenesis. Anti vascular endothelial growth factor (Anti-VEGF) therapy has been extensively studied and the studies have demonstrated its promising role early stages of ROP. The role of Insulin like growth factor (IGF), Granulocyte colony stimulating factor (GCSF), and June kinases (JNK) inhibitors are being studied by various researchers across the world. Gene therapy holds promise in the reversal of ROP changes.     

A dose comparison study between XVI and OBI CBCT systems

The purpose of this study is to establish a comprehensive set of dose measurements data obtained from the X-ray Volumetric Imager (XVI, Elekta Oncology Systems) and the On-Board Imager (OBI, Varian Medical Systems) cone-beam CT (CBCT) systems. To this end, two uniform-density cylindrical acrylic phantoms with diameters of 18 cm (head phantom) and 30 cm (body phantom) were used for all measurements. Both phantoms included ion chamber placement holes in the center and at periphery (2 cm below surface). For the XVI unit, the four standard manufacturer-supplied protocols were measured. For the OBI unit, the full bow tie and half bow tie (and no bow tie) filters were used in combination with the two scanning modes; namely, full-fan and half-fan. The total milliampere x seconds (mA s) setting was also varied for each protocol to establish the linear relationship between the dose deposited and the mA s used (with all other factors being held constant). Half-value layers in aluminum (Al) were also measured for beam characteristic determination. For the XVI unit, the average dose ranged from 0.1 to 3.5 cGy with the highest dose measured using the "prostate" protocol with the body phantom. For the OBI unit, the average dose ranged from 1.1 to 8.3 cGy with the highest dose measured using the full-fan protocol with the head phantom. The measured doses were highly linear as a function of mA s, for both units, where the measurement points followed a linear relationship very closely with R2 > 0.99 for all cases. Half-value layers were between 4.6- and 7.0-mm-Al for the two CBCT units where XVI generally had more penetrating beams at the similar kVp settings. In conclusion, a comprehensive series of dose measurements were performed on the XVI and the OBI CBCT units. In the process, many of the important similarities and differences between the two systems were observed and summarized in this work.     

Electroporation delivery of DNA vaccines: prospects for success

A number of noteworthy technology advances in DNA vaccines research and development over the past few years have led to the resurgence of this field as a viable vaccine modality. Notably, these include--optimization of DNA constructs; development of new DNA manufacturing processes and formulations; augmentation of immune responses with novel encoded molecular adjuvants; and the improvement in new in vivo delivery strategies including electroporation (EP). Of these, EP mediated delivery has generated considerable enthusiasm and appears to have had a great impact in vaccine immunogenicity and efficacy by increasing antigen delivery upto a 1000 fold over naked DNA delivery alone. This increased delivery has resulted in an improved in vivo immune response magnitude as well as response rates relative to DNA delivery by direct injection alone. Indeed the immune responses and protection from pathogen challenge observed following DNA administration via EP in many cases are comparable or superior to other well studied vaccine platforms including viral vectors and live/attenuated/inactivated virus vaccines. Significantly, the early promise of EP delivery shown in numerous pre-clinical animal models of many different infectious diseases and cancer are now translating into equally enhanced immune responses in human clinical trials making the prospects for this vaccine approach to impact diverse disease targets tangible.     

TLR7 and TLR9 trigger distinct neuroinflammatory responses in the CNS

Toll-like receptors (TLRs) 7 and 9 recognize nucleic acid determinants from viruses and bacteria and elicit the production of type I interferons and proinflammatory cytokines. TLR7 and TLR9 are similar regarding localization and signal transduction mechanisms. However, stimulation of these receptors has differing effects in modulating viral pathogenesis and in direct toxicity in the central nervous system (CNS). In the present study, we examined the potential of the TLR7 agonist imiquimod and the TLR9 agonist cytosine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) to induce neuroinflammation after intracerebroventricular inoculation. CpG-ODN induced a more robust inflammatory response than did imiquimod after inoculation into the CNS, with higher levels of several proinflammatory cytokines and chemokines. The increase in cytokines and chemokines correlated with breakdown of the blood-cerebrospinal fluid barrier and recruitment of peripheral cells to the CNS in CpG-ODN-inoculated mice. In contrast, TLR7 agonists induced a strong interferon β response in the CNS but only low levels of other cytokines. The difference in response to these agonists was not due to differences in distribution or longevity of the agonists but rather was correlated with cytokine production by choroid plexus cells. These results indicate that despite the high similarity of TLR7 and TLR9 in binding nucleic acids and inducing similar downstream signaling, the neuroinflammation response induced by these receptors differs dramatically due, at least in part, to activation of cells in the choroid plexus.     

Impact of the RHANI Wives intervention on marital conflict and sexual coercion

Objective

To assess the effects of the RHANI (Reducing HIV among Non-Infected) Wives intervention on marital conflict and intimate partner violence (IPV) in urban India.

Methods

A 2-armed cluster-randomized controlled trial (7 intervention, 6 control clusters) of the RHANI Wives intervention was conducted with 220 women contending with a history of IPV and/or husband’s drunken behavior. Participants were surveyed at baseline and 4.5-month follow-up. Outcome measures included marital conflict (arguments with husband in past 3 months), marital IPV (physical or sexual violence from husband in past 3 months), and marital sexual coercion (husband forcing sex at last sex). Intention-to-treat logistic generalized linear mixed models were used to determine intervention impact.

Results

One-third (35.0%) of participants reported physical or sexual abuse from their husband in the past 3 months, and 58.6% reported that their husband was drunk in the past 30 days. Intention-to-treat analyses indicated time × treatment reductions in marital conflict (risk ratio [RR] 0.4; 90% confidence interval [CI], 0.1–0.9; P = 0.06) and marital sexual coercion (RR 0.2; 90% CI, 0.05–0.9; P = 0.08), but not IPV.

Conclusion

The findings suggest the potential utility of this intervention in reducing marital conflict and sexual coercion among women in urban India.ClinicalTrials.gov: NCT01592994.     

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study

Background:

Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world.

Objectives:

The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years.

Materials and Methods:

In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded.

Results:

The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI.

Conclusions:

Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.     

Cerebral blood flow, cross-brain oxygen extraction, and fontanelle pressure after hypoxic-ischemic injury in newborn infants

The relationship between mean arterial pressure, intracranial pressure, cerebral blood flow, cross-brain oxygen extraction, cerebral metabolic rate, and outcome was studied during therapy in nine neonates on 3 consecutive days after severe hypoxic-ischemic cerebral injury. Cross-brain oxygen extraction was significantly higher (5.06 +/- 0.5 vs 2.05 +/- 0.8 ml/dl; p = 0.012) in the five neonates who survived with normal neurologic outcome than in the four who died or sustained severe brain damage. In contrast, global cerebral blood flow in the five neonates with normal neurologic outcome was significantly lower (25.6 +/- 8.2 vs 83.2 +/- 44.9 ml/100 gm brain/min; p less than 0.05) during the study period. The differences in cross-brain oxygen extraction and global cerebral blood flow between infants who had neurologic recovery and those who died or sustained brain damage occurred in the presence of acceptable values for intracranial pressure, mean arterial pressure, and cerebral perfusion pressure. Our preliminary data suggest that cross-brain oxygen extraction and possibly global cerebral blood flow may be important variables associated with severe neuronal injury and death after hypoxic-ischemic cerebral injury.     

Relationship of cross-brain oxygen content difference, cerebral blood flow, and metabolic rate to neurologic outcome after near-drowning.

We evaluated the relationship of global cerebral blood flow, cross-brain oxygen content difference, cerebral metabolic rate for oxygen, intracranial pressure, and cerebral perfusion pressure to functional neurologic outcome in 12 comatose children on 2 consecutive days after near-drowning. Five children survived with functional neurologic outcome; five died and two survived with severe neurologic damage. Children who survived with functional neurologic outcome had a significantly higher cross-brain oxygen content difference (7.89 +/- 2.62 vs 3.91 +/- 1.59 ml/dl; p = 0.028) at 24 hours and a higher cerebral metabolic rate for oxygen 48 hours after admission (3.19 +/- 2.86 vs 0.96 +/- 0.45 ml/100 gm per minute; p = 0.030) compared with those who died or survived in a damaged state. There were no significant differences in global cerebral blood flow, intracranial pressure, and cerebral perfusion pressure between groups at either 24 or 48 hours. Our preliminary data suggest that a higher cross-brain content difference value is an important early variable associated with functional neurologic recovery after near-drowning. However, a single cross-brain oxygen content difference value must be interpreted with caution because considerable variability may occur among patient groups.