Deconvoluting lung evolution using functional/comparative genomics

Parathyroid Hormone-related Protein (PTHrP) is a highly evolutionarily conserved, stretch-regulated gene that is necessary for the embryonic transition from branching morphogenesis to alveolization of the lung. It is expressed throughout vertebrate phylogeny, beginning with its expression in the fish swim bladder as an adaptation to gravity; microgravity downregulates the expression of PTHrP by alveolar type II cells, and by bones from rats exposed to 0 x g, suggesting that PTHrP signaling has been exploited for adaptation to 1 x g. PTHrP/PTHrP receptor signaling is upregulated by stretching alveolar type II cells and intersitial lung fibroblasts, whereas overdistension downregulates PTHrP and PTHrP receptor mRNA, further suggesting an evolutionary adaptation. Both surfactant homeostasis and alveolar capillary perfusion are under PTHrP control, indicating that alveolization and ventilation/perfusion matching may have evolved under the influence of PTHrP signaling. Phylogenetic analysis of lung evolution reflects the concomitant increases in alveolar surface area and surfactant production by "amplifying" the PTHrP pathway signal. This mechanism is discussed as a function of increased evolutionary respiratory demand to keep up with the increased metabolic demand for oxygen, and the role of the PTHrP signaling mechanism in leveraging this process.     

Online health communities,contributions to caregivers and resilience of older adults

The aim of this paper is twofold. Firstly, to investigate the potential benefits of online health communities (OHCs) for informal caregivers by conducting a systematic literature review. Secondly, to identify the relationship between the potential benefits of OHCs and resilience factors of older adults. Performing a thematic analysis, we identified the potential benefits of OHCs for informal caregivers of older adults, including two salient themes: (a) caregivers sharing and receiving social support and (b) self and moral empowerment of caregivers. Then, we uncovered how these potential benefits can support resilience of older adults. Our findings show that sharing and receiving of social support by informal caregivers, and self and moral empowerment of informal caregivers in OHCs, can support four resilience factors among older adults, including self-care, independence, altruism and external connections. This review enables a better understanding of OHCs and Gerontology, and our outcomes also challenge the way healthcare and aged-care service providers view caregivers and older adults. Furthermore, the identified gap and opportunities would provide avenues for further research in OHCs.     

Concurrent cisplatin and radiotherapy in advanced head and neck cancer

Management of Head and Neck Cancers poses a challenge inspite of several advances because of poor success in terms of response rate, survival and reduced morbidity of the patients. In the present study 30 untreated histologically proven cases of head and neck cancers were subjected to weekly radiotherapy with adjuvant chemotherapy (cisplatin 30 mg/m² intravenously). This study group was compared with a group of 30 patients who were given only radiotherapy. Results have shown that combination of chemotherapy with radiotherapy gives a significantly better results in tumour as well as nodal response with minimal toxicities.     

Multi-Objective Optimization of Process Parameters during Micro-Milling of Nickel-Based Alloy Inconel 718 Using Taguchi-Grey Relation Integrated Approach

This research investigates the machinability of Inconel 718 under conventional machining speeds using three different tool coatings in comparison with uncoated tool during milling operation. Cutting speed, feed rate and depth of cut were selected as variable machining parameters to analyze output responses including surface roughness, burr formation and tool wear. It was found that uncoated and AlTiN coated tools resulted in lower tool wear than nACo and TiSiN coated tools. On the other hand, TiSiN coated tools resulted in highest surface roughness and burr formation. Among the three machining parameters, feed was identified as the most influential parameter affecting burr formation. Grey relational analysis identified the most optimal experimental run with a speed of 14 m/min, feed of 1 μm/tooth, and depth of cut of 70 μm using an AlTiN coated tool. ANOVA of the regression model identified the tool coating parameter as most effective, with a contribution ratio of 41.64%, whereas cutting speed and depth of cut were found to have contribution ratios of 18.82% and 8.10%, respectively. Experimental run at response surface optimized conditions resulted in reduced surface roughness and tool wear by 18% and 20%, respectively.     

Platelet inhibition by aspirin 81 and 325 mg/day in men versus women without clinically apparent cardiovascular disease

Compared with men, women have greater platelet aggregation before and after low-dose aspirin. It is not known whether high-dose aspirin therapy brings residual platelet aggregation in women closer to that in men. Our objective was to compare inhibition of platelet aggregation in women and men after low- and high-dose aspirin. We enrolled healthy subjects (n=106) in a trial of 14 days of aspirin 81 mg/day followed by 14 days of 325 mg/day. Platelet function was measured at baseline and after the 2 aspirin doses. Women had greater baseline platelet activation measurements. After the 2 aspirin doses, men and women had near complete suppression of platelet aggregation to arachidonic acid in whole blood and in platelet-rich plasma (PRP), the direct cyclo-oxygenase-1 pathway affected by aspirin. For indirect pathways, women had significantly greater residual platelet activation to collagen and adenosine diphosphate (ADP) in whole blood after the 2 aspirin doses and in response to collagen and ADP in PRP after aspirin 325 mg/day only. After aspirin 325 mg/day, women continued to have greater residual platelet aggregation compared with men after aspirin 81 mg/day in response to collagen (p=0.016 in whole blood, p=0.037 in PRP), ADP (p<0.001 in whole blood, p=0.012 in PRP), and epinephrine (p=0.03 in PRP). Excretion of urinary thromboxane metabolite (urinary 11-dehydrothromboxane B2) decreased after aspirin to a similar extent in men and women. In conclusion, women continue to have greater residual platelet activity after high-dose aspirin compared with men treated with a lower dose of aspirin.     

Comparison of Aqueous Humour Concentration after Single High Dose Versus Multiple Administration of Topical Moxifloxacin in Rabbits

For the prevention of postoperative ocular infections prophylactic topical antibiotics are routinely used. Studies evaluating comparative difference between single dose versus multiple dose administration on aqueous humour concentration of moxifloxacin are lacking. This study compared the aqueous humour concentration of moxifloxacin following its topical administration in rabbit eyes with two dose regimens. Twelve albino rabbits were divided into two groups. In group-1, two drops were administered thrice (total six drops) at 2 min intervals, in both the eyes; in group-2, two drops of moxifloxacin were administered three times a day for three days and also two h before aqueous humour collection i.e. on fourth day. Mean aqueous humour concentrations were calculated and compared using Student''s ‘t’ test and P<0.05 was considered significant. Moxifloxacin concentration in aqueous humour in group-1 was 23.79 μg/ml and in group-2 was 42.08 μg/ml. Both dosing regimens produced substantially higher aqueous concentrations than the known minimum inhibitory concentration for most bacteria. Moxifloxacin concentration in aqueous humour with multiple instillations is significantly higher than single instillation (P<0.05), which is adequate to cover ciprofloxacin-resistant gram-negative bacteria. Repeated topical moxifloxacin administration achieved significantly higher aqueous humour concentrations than single administration.     

Conjoint bicondylar Hoffa fracture in an adult

Conjoint bicondylar Hoffa fracture is an extremely rare injury. Only one case has been reported previously in the pediatric age group. We describe this injury in a 17-year-old male who presented following a fall with direct impact on his semiflexed right knee. Plain radiographs were inadequate to define the exact pattern of injury. Computed tomographic (CT) scans demonstrated the coronal fracture involving both the femoral condyles which were joined by a bridge of intact bone. The patient was treated with open reduction and internal fixation using swashbuckler (modified anterior) approach. Union occurred within 3 months and at final followup (at 18 months) the patient had a good clinical outcome. The possible mechanism of injury is discussed.