Growth hormone therapy is associated with improved uterine dimensions in girls with Turner syndrome prior to oestrogen replacement.

BACKGROUND: Adult women with Turner syndrome (TS) have high rates of miscarriage, presumably due to the abnormal size and shape of the uterus. There is a paucity of data regarding the determinants of uterine volume (UtVol) in young girls with TS before the initiation of oestrogen replacement therapy (ERT). METHODS: We performed a cross-sectional study on premenarchal girls with TS, aged 5-15 years, pubertal stage B1-B3, not having received ERT (n = 73) and 50 age-matched healthy controls. Anthropometric parameters and a history of growth hormone (GH) therapy (≥1 year) were noted. Uterine length (UtL), UtVol, and mean-ovarian-volume (MOV) standard-deviation scores (SDS) were determined from transabdominal ultrasonography data. RESULTS: Girls with TS had lower median UtVol-SDS (-1.07 vs. 0.86; p < .001), UtL-SDS (-3.72 vs. -0.41; p < .001) and MOV-SDS (-5.53 vs. 1.96; p < .001) compared to age-matched controls. Among TS girls, recipients of GH (n = 38) had higher UtVol-SDS (-0.63 vs. -1.39; p = .0001), UtL-SDS (-1.73 vs. -6.49; p < .0001) but similar MOV-SDS compared to nonrecipients (n = 35). Those with normal uterine volume for age (NUVA, n = 29) had earlier initiation (7.8 vs. 9.3 years; p = .03) and a longer duration of GH (3.71 vs. 2.14 years; p = .002) than those with low UtVol for age (n = 44). UtVol-SDS correlated with duration of GH (ρ = 0.411, p = .01) and negatively with age at GH initiation (ρ = -0.479, p = .003). In a model adjusted for pubertal status, karyotype and height-SDS, GH use could independently predict having NUVA (odds ratio: 5.09, confidence interval: 1.63-15.94, p = .005). CONCLUSION: GH therapy has a stimulatory effect on uterine dimensions in pre-and peripubertal girls with TS. Earlier initiation and longer duration of GH is important in TS girls before ERT.

3-Substituted 1-Naphthamidomethyl-C-galactosyls Interact with Two Unique Sub-sites for High-Affinity and High-Selectivity Inhibition of Galectin-3.

The galectins are a family of galactose-binding proteins playing key roles in inflammatory processes and cancer. However, they are structurally very closely related, and discovery of highly selective inhibitors is challenging. In this work, we report the design of novel inhibitors binding to a subsite unique to galectin-3, which confers both high selectivity and affinity towards galectin-3. Olefin cross metathesis between allyl ß-C-galactopyranosyl and 1-vinylnaphthalenes or acylation of aminomethyl ß-C-galactopyranosyl with 1-naphthoic acid derivatives gave C-galactopyranosyls carrying 1-naphthamide structural elements that interacted favorably with a galectin-3 unique subsite according to molecular modeling and X-ray structural analysis of two inhibitor-galectin-3 complexes. Affinities were down to sub-µM and selectivities over galectin-1, 2, 4 N-terminal domain, 4 C-terminal domain, 7, 8 N-terminal domain, 9 N-terminal domain, and 9 C-terminal domain were high. These results show that high affinity and selectivity for a single galectin can be achieved by targeting unique subsites, which holds promise for further development of small and selective galectin inhibitors.

New Strategy for in Vitro Determination of Carbonic Anhydrase Activity from Analysis of Oxygen-18 Isotopes of CO2.

The oxygen-18 isotopic (18O) composition in CO2 provides an important insight into the variation of rate in isotopic fractionation reaction regulated by carbonic anydrase (CA) metalloenzyme. This work aims to employ an 18O-isotope ratio-based analytical method for quantitative estimation of CA activity in erythrocytes for clinical testing purposes. Here, a new method has been developed that contains the measurements of 18O/16O isotope ratios during oxygen-18 isotopic exchange between 12C16O16O and H218O of an in vitro biochemical reaction controlled by erythrocytes CA and estimation of enzymatic activity of CA from the isotopic composition of CO2. We studied the enrichments of 18O-isotope of CO2 with increments of CA activities during isotopic fractionation reaction. To check the influence of subject-specific body temperature, pH, H218O, and cellular produced CO2 on this reaction, we performed the in vitro experiments in closed containers with variations of those parameters. Finally, we mimicked the exchange reaction at 5% [CO2], 5‰ [H218O], pH of 7.4, and temperature of 37 °C to create the physiological environment equivalent to that of the human body and monitored the exchange kinetics with variations of CA activities, and subsequently, we derived the quantitative relation between the 18O-isotope of CO2 and CA activity in erythrocytes. This assay may be applicable for rapid and simple quantification of carbonic anhydrase activity which is very important to prevent the carbonic-anhydrase-associated disorders in human.

High-resolution spectral analysis of ammonia near 6.2 µm using a cw EC-QCL coupled with cavity ring-down spectroscopy.

We report on the development of a mid-infrared cavity ring-down spectrometer (CRDS) coupled with a continuous wave (cw) external cavity quantum cascade laser (EC-QCL), operating between 6.0 µm and 6.3 µm, for high-resolution spectroscopic studies of ammonia (NH3) which served as a bench-mark molecule in this spectral region. We characterized the EC-QCL based CRDS system in detail and achieved a noise-equivalent absorption (NEA) coefficient of 2.11 × 10-9 cm-1 Hz-1/2 for a 100 Hz data acquisition rate. We thereafter exploited the system for high-resolution spectroscopic analysis of interference-free 10 transition lines of the ν4 fundamental vibrational band of NH3 centred at ∼6.2 µm. We probed the strongest interference-free absorption line RQ(4,3) of ν4, centred at 1613.370 cm-1 for highly-sensitive trace detection of NH3 and subsequently achieved a minimum detection sensitivity (1σ) of 2.78 × 109 molecules per cm3 which translated into the detection limit of 740 parts-per-trillion by volume (pptv/10-12) at a pressure of 115 Torr for an integration time of ∼167 seconds. To demonstrate the efficacy of the present system in real-life applications, we finally measured the mixing ratios of NH3 present in ambient air and human exhaled breath with high sensitivity and molecular specificity.

Bottom-Up Elucidation of Glycosidic Bond Stereochemistry.

The lack of robust, high-throughput, and sensitive analytical strategies that can conclusively map the structure of glycans has significantly hampered progress in fundamental and applied aspects of glycoscience. Resolution of the anomeric α/ß glycan linkage within oligosaccharides remains a particular challenge. Here, we show that "memory" of anomeric configuration is retained following gas-phase glycosidic bond fragmentation during tandem mass spectrometry (MS2). These findings allow for integration of MS2 with ion mobility spectrometry (IM-MS2) and lead to a strategy to distinguish α- and ß-linkages within natural underivatized carbohydrates. We have applied this fragment-based hyphenated MS technology to oligosaccharide standards and to de novo sequencing of purified plant metabolite glycoconjugates, showing that the anomeric signature is also observable in fragments derived from larger glycans. The discovery of the unexpected anomeric memory effect is further supported by IR-MS action spectroscopy and ab initio calculations. Quantum mechanical calculations provide candidate geometries for the distinct anomeric fragment ions, in turn shedding light on gas-phase dissociation mechanisms of glycosidic linkages.

Label-Free Discovery Array Platform for the Characterization of Glycan Binding Proteins and Glycoproteins.

The identification of carbohydrate-protein interactions is central to our understanding of the roles of cell-surface carbohydrates (the glycocalyx), fundamental for cell-recognition events. Therefore, there is a need for fast high-throughput biochemical tools to capture the complexity of these biological interactions. Here, we describe a rapid method for qualitative label-free detection of carbohydrate-protein interactions on arrays of simple synthetic glycans, more complex natural glycosaminoglycans (GAG), and lectins/carbohydrate binding proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The platform can unequivocally identify proteins that are captured from either purified or complex sample mixtures, including biofluids. Identification of proteins bound to the functionalized array is achieved by analyzing either the intact protein mass or, after on-chip proteolytic digestion, the peptide mass fingerprint and/or tandem mass spectrometry of selected peptides, which can yield highly diagnostic sequence information. The platform described here should be a valuable addition to the limited analytical toolbox that is currently available for glycomics.

Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition.

Discovery of glycan-competitive galectin-3-binding compounds that attenuate lung fibrosis in a murine model and that block intracellular galectin-3 accumulation at damaged vesicles, hence revealing galectin-3-glycan interactions involved in fibrosis progression and in intracellular galectin-3 activities, is reported. 3,3'-Bis-(4-aryltriazol-1-yl)thiodigalactosides were synthesized and evaluated as antagonists of galectin-1, -2, -3, and -4 N-terminal, -4 C-terminal, -7 and -8 N-terminal, -9 N-terminal, and -9 C-terminal domains. Compounds displaying low-nanomolar affinities for galectins-1 and -3 were identified in a competitive fluorescence anisotropy assay. X-ray structural analysis of selected compounds in complex with galectin-3, together with galectin-3 mutant binding experiments, revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectin-3. The most potent galectin-3 antagonist was demonstrated to act in an assay monitoring galectin-3 accumulation upon amitriptyline-induced vesicle damage, visualizing a biochemically/medically relevant intracellular lectin-carbohydrate binding event and that it can be blocked by a small molecule. The same antagonist administered intratracheally attenuated bleomycin-induced pulmonary fibrosis in a mouse model with a dose/response profile comparing favorably with that of oral administration of the marketed antifibrotic compound pirfenidone.

ChatGPT: Literate or intelligent about UN sustainable development goals?

Generative AI tools, such as ChatGPT, are progressively transforming numerous sectors, demonstrating a capacity to impact human life dramatically. This research seeks to evaluate the UN Sustainable Development Goals (SDGs) literacy of ChatGPT, which is crucial for diverse stakeholders involved in SDG-related policies. Experimental outcomes from two widely used Sustainability Assessment tests-the UN SDG Fitness Test and Sustainability Literacy Test (SULITEST) - suggest that ChatGPT exhibits high SDG literacy, yet its comprehensive SDG intelligence needs further exploration. The Fitness Test gauges eight vital competencies across introductory, intermediate, and advanced levels. Accurate mapping of these to the test questions is essential for partial evaluation of SDG intelligence. To assess SDG intelligence, the questions from both tests were mapped to 17 SDGs and eight cross-cutting SDG core competencies, but both test questionnaires were found to be insufficient. SULITEST could satisfactorily map only 5 out of 8 competencies, whereas the Fitness Test managed to map 6 out of 8. Regarding the coverage of the Fitness Test and SULITEST, their mapping to the 17 SDGs, both tests fell short. Most SDGs were underrepresented in both instruments, with certain SDGs not represented at all. Consequently, both tools proved ineffective in assessing SDG intelligence through SDG coverage. The study recommends future versions of ChatGPT to enhance competencies such as collaboration, critical thinking, systems thinking, and others to achieve the SDGs. It concludes that while AI models like ChatGPT hold considerable potential in sustainable development, their usage must be approached carefully, considering current limitations and ethical implications.

Effects of the multiscale porosity of decellularized platelet-rich fibrin-loaded zinc-doped magnesium phosphate scaffolds in bone regeneration.

In recent years, metallic ion-doped magnesium phosphate (MgP)-based degradable bioceramics have emerged as alternative bone substitute materials owing to their excellent biocompatibility, bone-forming ability, bioactivity, and controlled degradability. Conversely, incorporating a biomolecule such as decellularized platelet-rich fibrin (d-PRF) on scaffolds has certain advantages for bone tissue regeneration, particularly in enhanced osteogenesis and angiogenesis. The present study focuses on the impact of d-PRF-loaded multiscale porous zinc-doped magnesium phosphate (Zn-MgP) scaffolds on biodegradability, biocompatibility, and bone regeneration. Scaffolds were fabricated through the powder-metallurgy route utilizing naphthalene as a porogen (porosity = 5-43%). With the inclusion of a higher porogen, a higher fraction of macro-porosity (>20 µm) and pore interconnectivity were observed. X-ray diffraction (XRD) studies confirmed the formation of the farringtonite phase. The developed scaffolds exhibited a minimum ultimate compressive strength (UCS) of 8.5 MPa (for 40 Naph), which lies within the range of UCS of the cancellous bone of humans (2-12 MPa). The in vitro assessment via immersion in physiological fluid yielded a higher deposition of the calcium phosphate (CaP) compound in response to increased macro-porosity and interconnectivity (40 Naph). Cytocompatibility assessed using MC3T3-E1 cells showed that the incorporation of d-PRF coupled with increased porosity resulted the highest cell attachment, proliferation, and viability. For further evaluation, the developed scaffolds were implanted in in vivo rabbit femur condylar defects. Radiography, SEM, OTC labelling, and histology analysis after 2 months of implantation revealed the better invasion of mature osteoblastic cells into the scaffolds with enhanced angiogenesis and superior and accelerated healing of bone defects in d-PRF-incorporated higher porosity scaffolds (40 Naph). Finally, it is hypothesized that the combination of d-PRF incorporation with multiscale porosity and increased interconnectivity facilitated better bone-forming ability, good biocompatibility, and controlled degradability within and around the Zn-doped MgP scaffolds.

Synergistic Improvement of Antibacterial and Osteogenic Differentiation of Thermomechanically Processed Mg-Zr-Sr-Ce Alloy: Insights into the Role of Precipitate Evolution Supported by AIMD Simulation Study.

In the present study, we have discussed the influence of forging temperature (623 K (FT623), 723 K (FT723) and 823 K (FT823)) on microstructure and texture evolution and its implication on mechanical behavior, in vitro-in vivo biocorrosion, antibacterial response, and cytocompatibility of microalloyed Mg-Zr-Sr-Ce alloy. Phase analysis, SEM, and TEM characterization confirm the presence of Mg12Ce precipitate, and its stability was further validated by performing ab initio molecular dynamic simulation study. FT723 exhibits strengthened basal texture, higher fraction of second phases, and particle-stimulated nucleation-assisted DRX grains compared to other two specimens, resulting in superior strength with comparable ductility. FT723 also exhibits superior corrosion resistance mainly due to the strengthened basal texture and lower dislocation density. All the specimens exhibit excellent antibacterial behavior with Gram-negative E. coli, Gram-positive Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. 100% reduction of bacterial growth is observed within 24 h of culture of the specimens. Cytocompatibility was determined by challenging specimen extracts with the MC3T3-E1 cell lines. FT723 specimen exhibits the highest cell proliferation and alkaline phosphatase activity (ALP) because of its superior corrosion resistance. The ability of the specimens to be used in orthopedic implant application was evaluated by in vivo study in rabbit femur. Neither tissue-related infection nor the detrimental effect surrounding the implant was confirmed from histological analysis. Significant higher bone regeneration surrounding the FT723 specimen was observed in SEM analysis and fluorochrome labeling. After 60 days, the FT723 specimen exhibits the highest bone formation, suggesting it is a suitable candidate for orthopedic implant application.

Real-world outcomes and complications of different surgical approaches for significant submacular haemorrhages.

Purpose: To evaluate the outcomes and complications after different surgical management of cases with significant sumacular hemorrhage (SMH) of size more than 4 disc diameter (DD). Methods: It was a retrospective interventional study. All consecutive 103 cases of significant SMHs were treated by vitrectomy and divided into three groups. In Group A (<4 weeks, confined to the macula or extending inferiorly, n = 62), vitrectomy, subretinal cocktail of tissue plasminogen activator (tPA), antivascular endothelial growth factor, and air with SF6 gas; in Group B (4-8 weeks, extending beyond macula, n = 31), subretinal tPA followed by SMH drainage either by retinotomy (Group B-1, n = 17) or by temporal 180-degree retinectomy (Group B-2, n = 14) with silicone oil (SO) tamponade; and in Group C (>8 weeks, extending beyond macula, n = 10), SMH removal with autologous retinal pigment epithelium (RPE)-Choroid patch graft transplantations with SO tamponade were performed. Parameters evaluated were best corrected visual acuity (BCVA), Optos, optical computerized tomography, and ultrasonography as required. Results: Significant visual improvement was seen from mean preoperative to mean postoperative BCVA in Group A (P < 0.001), Group B (P < 0.001), and Group C (P < 0.001). Postoperative complications were recurrent SMH (4.84% vs 12.90% vs 10%), vitreous hemorrhage (6.45%, GroupA), hyphema (4.84% vs 12.90% vs 10%), hypotony (nil vs 3.23% vs 20%), macular hole formation (6.45%, Group A), epiretinal membrane (16.13%, Group B), and retinal detachment (3.23%, Group A and 10%, Group C). Conclusion: Surgical approaches for significant submacular hemorrhage are visually awarding, though certain specific complications may arise.

In vitro and in vivo assessment of decellularized platelet-rich fibrin-loaded strontium doped porous magnesium phosphate scaffolds in bone regeneration.

The present work reports the effect of decellularized platelet-rich fibrin (dPRF) loaded strontium (Sr) doped porous magnesium phosphate (MgP) bioceramics on biocompatibility, biodegradability, and bone regeneration. Sustained release of growth factors from dPRF is a major objective here, which conformed to the availability of dPRF on the scaffold surface even after 7 days of in vitro degradation. dPRF-incorporated MgP scaffolds were implanted in the rabbit femoral bone defect and bone rejuvenation was confirmed by radiological examination, histological examination, fluorochrome labeling study, and micro-CT. µ-CT examination of the regained bone samples exhibited that invasion of mature bone in the pores of the MgP2Sr-dPRF sample was higher than the MgP2Sr which indicated better bone maturation capability of this composition. Quantifiable assessment using oxytetracycline labeling showed 73.55 ± 1.12% new osseous tissue regeneration for MgP2Sr-dPRF samples in contrast to 65.47 ± 1.16% for pure MgP2Sr samples, after 3 months of implantation. Histological analysis depicted the presence of abundant osteoblastic and osteoclastic cells in dPRF-loaded Sr-doped MgP samples as compared to other samples. Radiological studies also mimicked similar results in the MgP2Sr-dPRF group with intact periosteal lining and significant bridging callus formation. The present results indicated that dPRF-loaded Sr-doped magnesium phosphate bioceramics have good biocompatibility, bone-forming ability, and suitable biodegradability in bone regeneration.

Controlled nano Cu precipitation through age treatment: A method to enhance the biodegradation, mechanical, antimicrobial properties and biocompatibility of Fe-20Mn-3Cu alloys.

Iron-manganese (Fe-Mn) based degradable biomaterials have been proven as a suitable substitute to permanent internal fracture-fixation devices. However, lower degradation and bacterial infection are still major concerns. To overcome these limitations, in this work, we have incorporated copper (Cu) in Fe-Mn system. The objective is to produce Cu nano-precipitates and refined microstructure through suitable combination of cold-rolling and age-treatment, so that degradation is improved eventually. High resolution transmission electron microscope (TEM) and scanning transmission electron microscope (STEM) confirmed the Cu rich composition of the nano-precipitates. Number of precipitates increased as aging time increased. Three-dimensional visualization of Fe, Mn and Cu atomic distributions using atom probe tomography (APT), indicated that Cu precipitates were in 15-50 nm range. Large number of nano-precipitates along with lower dislocation density led to highest strength (1078 MPa) and ductility (37 %) for the 6 h age-treated sample. On the other hand, nano-precipitates and refined microstructure resulted highest degradation for the 12 h of age treated sample (0.091 mmpy). When E.Coli bacteria was cultured with the sample extract, significantly higher antibacterial efficacy was observed for the sample having higher nano-precipitates. Higher degradation rate did not cause cyto-toxicity, rather promoted statistically higher cell proliferation (1.5 times within 24 h) in in vitro cell-material interaction studies. In vivo biocompatibility of the alloy containing large nano-precipitates was confirmed from higher new bone regeneration (60%) in rabbit femur model. Overall study suggested that the optimization of the thermo-mechanical processes can effectively tailor the Fe-Mn-Cu alloys for successful internal fracture fixation. STATEMENT OF SIGNIFICANCE: In the present work, we have reported a noble thermo-mechanical approach to simultaneously achieve Cu nano-precipitates and grain refinement in Fe-20Mn-3Cu alloy.

Synergistic Effects of Cerium and Hot Forging on Biodegradation, Antibacterial Properties, and In Vivo Biocompatibility of Microalloyed Mg-Zr-Sr Alloys.

Biodegradable magnesium (Mg)-based alloys are potential candidates for orthopedic applications. In the present study, we have discussed the effect of cerium (Ce) addition and hot forging on mechanical properties, in vitro-in vivo corrosion, antibacterial activity, and cytocompatibility of microalloyed Mg-0.2Zr-0.1Sr-xCe (x = 0 [MZS], 0.5 wt % [MZS-Ce]) alloys. Addition of 0.5 wt % Ce to forged MZS alloys leads to strengthening of the basal texture as well as formation of a higher fraction of dynamic recrystallized (DRX) grains. Hot forging and addition of cerium to the MZS alloy improve both the yield strength and ultimate tensile strength of the forged MZS-Ce alloy by 1.39 and 1.21 times, respectively, compared to those of the forged MZS alloy. The potentiodynamic polarization test in Hank's solution indicates that the corrosion resistance of the forged MZS alloy improves with addition of 0.5 wt % Ce. Uniform distribution of Mg12Ce precipitates, a higher DRX fraction, strengthened texture, and formation of a compact CeO2 passive layer result in 1.68 times reduction in the immersion corrosion rate of the forged MZS-Ce alloy compared to that of the forged MZS alloy. Addition of Ce to the MZS alloy shows excellent antibacterial activity. The forged MZS-Ce alloy exhibited the highest antibacterial efficacy (76.73%). All the alloys show favorable cytocompatibility and alkaline phosphatase (ALP) activity with MC3T3-E1 cells. The improved corrosion resistance of the forged MZS-Ce alloy (95%) leads to higher cell viability compared to that of the forged MZS alloy (85%). In vivo biodegradation and the ability to generate new bones were analyzed by implanting cylindrical samples in the rabbit femur. Histological analysis showed no adverse effects around the implants. Gradual degradation of the implants and higher new bone formation around the forged MZS-Ce sample were confirmed by micro-CT analysis. Bone regeneration around the implants (58.21%) was validated by flurochrome labeling. After 60 days, the forged MZS-Ce alloy showed controlled corrosion and better bone-implant integration, presenting it as a potential candidate for internal fracture fixation materials.

In Vitro and In Vivo Bone Regeneration Assessment of Titanium-Doped Waste Eggshell-Derived Hydroxyapatite in the Animal Model.

In this work, a titanium-doped hydroxyapatite (HAp) scaffold was produced from two different sources (natural eggshell and laboratory-grade reagents) to compare the efficacy of natural and synthetic resources of HAp materials on new bone regeneration. This comparative study also reports the effect of Ti doping on the physical, mechanical, and in vitro as well as in vivo biological properties of the HAp scaffold. Pellets were prepared in the conventional powder metallurgy route, compacted, and sintered at 900 °C, showing sufficient porosity for bony ingrowth. The physical-mechanical characterizations were performed by density, porosity evaluation, XRD, FTIR, SEM analysis, and hardness measurement. In vitro interactions were evaluated by bactericidal assay, hemolysis, MTT assay, and interaction with simulated body fluid. All categories of pellets showed absolute nonhemolytic and nontoxic character. Furthermore, significant apatite formation was observed on the Ti-doped HAp samples in the simulated body fluid immersion study. The developed porous pellets were implanted to assess the bone defect healing in the femoral condyle of healthy rabbits. A 2 month study after implantation showed no marked inflammatory reaction for any samples. Radiological analysis, histological analysis, SEM analysis, and oxytetracycline labeling studies depicted better invasion of mature osseous tissue in the pores of doped eggshell-derived HAp scaffolds as compared to the undoped HAp, and laboratory-made samples. Quantification using oxytetracycline labeling depicted 59.31 ± 1.89% new bone formation for Ti-doped eggshell HAp as compared to Ti-doped pure HAp (54.41 ± 1.93) and other undoped samples. Histological studies showed the presence of abundant osteoblastic and osteoclastic cells in Ti-doped eggshell HAp in contrast to other samples. Radiological and SEM data also showed similar results. The results indicated that Ti-doped biosourced HAp samples have good biocompatibility, new bone-forming ability, and could be used as a bone grafting material in orthopedic surgery.

Effects of multiscale porosity and pore interconnectivity on in vitro and in vivo degradation and biocompatibility of Fe-Mn-Cu scaffolds.

Iron (Fe) based scaffolds are promising candidates as degradable metallic scaffolds. High strength and ability to control the degradation with tailormade composition and porosity are specific advantages of these scaffolds. In this research work, iron-manganese-copper (Fe-Mn-Cu) based scaffolds, with multiscale porosity, are developed through a powder metallurgy route using naphthalene as a spacer material. The porosity in the scaffolds ranged from 42-76%, where the majority of the macro-pores (≥20 µm) form an interconnected channel network. XRD analysis confirms the presence of MRI compatible and antiferromagnetic austenite as a major phase in all the scaffolds. The developed scaffolds in this study have a minimum ultimate compressive strength of 7.21 MPa (for 30Naph), which lies within the range of the human cancellous bone UCS (2-12 MPa). The degradation rates of the scaffolds are determined from static immersion tests, where the scaffold with the highest porosity (76%) shows a highest degradation rate of 2.71 mmpy when immersed in Hank's balanced salt solution (HBSS) at 37 °C for 30 days. The increased degradation rate of the scaffolds has no cytotoxic effects on MG63 cells as studied by alamar blue assay and live/dead imaging. When implanted in a rabbit femur, the scaffold with higher porosity showed enhanced osteogenesis, as evident through micro-CT and histological analysis. It is hypothesized that the presence of multiscale porosity with a high degree of interconnectivity facilitated better bone regeneration within and around the Fe-Mn-Cu scaffolds.

Isotope-specific breath analysis to track the end-stage renal disease during hemodialysis.

The underlying mechanisms towards the progression of end-stage renal disease (ESRD) in chronic kidney disease (CKD) are poorly understood and it still remains a major clinical stumbling block for early detection of CKD. Most patients with CKD pass through ESRD with the necessity of frequent hemodialysis (HD) treatment. At present, plasma urea and creatinine levels are examined in most CKD patients to monitor their health status after dialysis. But it is impossible to get immediate feedback on the patients' health as the conventional tests involve the collection of blood samples, laboratory processing for a prolonged period of time and, finally, analysis of those samples. However, the test results are very important in deciding the treatment plan for those ESRD patients. Here, we show that the enzymatic activity of carbonic anhydrase in erythrocytes is distinctly altered in ESRD subjects under HD. This, in turn, leads to the isotopic enrichments of oxygen-18 (18O) and carbon-13 (13C) of CO2 during respiration in HD treatment. High-resolution cavity-enhanced absorption spectroscopic measurements show that 18O and 13C-isotopic fractionations of breath CO2 are correlated with Kt/V values, suggesting a novel unifying strategy for ESRD patients that can be used as an isotope-specific methodology for non-invasive assessment of dialysis adequacy and hence 12C18O16O and 13C16O16O could be used as novel markers for tracking the physiological parameters of ESRD individuals. Our findings suggest that the monitoring of 18O and 13C isotopes of breath CO2 may facilitate the proper management of advanced CKD patients. The primary advantage of this isotopic breath test is that it may reduce the valuable time lag between the completion of dialysis and obtaining the clinical report on the status of patients' health.

Double Posterior Based Flap Technique in Primary Endoscopic Dacryocystorhinostomy With and Without Using Powered Instrument.

To demonstrate the surgical technique and outcomes of double posterior based flap technique in primary endoscopic dacryocystorhinostomy (DCR) with and without use of powered instrument. 28 patients of nasolacrimal duct obstruction were included in the study from September 2012 to February 2015. All underwent endoscopic dacryocystorhinostomy with double posterior based nasal and lacrimal flap technique. In patients of group A (14 patients), bone removal was done with the help of Smith-Kerrison punch forceps and in patients of group B (14 patients), powered drill has been used for the same. Patients were visited the endoscopic clinic at 1, 3, 6 months and 1 year after the surgery for post operative evaluation. Of 28 patients, 26(92.85%) were found free of symptoms at the end of 1, 3 and at 6 months. One from each group had recurrence of symptoms. At the end of 12 months of 25 patients, 3(12%) patients were found to have recurrence of symptoms of which 1(8.33%) patients was from group A and 2(15.38%) were from group B and failures were because of granulation tissue and stomal stenosis. Patients assisted with powered drill had more postoperative complications compared to cold instrument. Double posterior based flap technique in primary endoscopic DCR without the assistance of powered drill could be an effective surgical option for the patients of chronic nasolacrimal duct obstruction enabling early epithelisation by preventing peristomal granulation tissue resulting in encouraging surgical outcome with least postoperative complication.

13C isotopic abundances in natural nutrients: a newly formulated test meal for non-invasive diagnosis of type 2 diabetes.

A new method to replace commercially prepared 13C-labelled glucose with naturally available 13C-enriched substrates could result in promotion of the clinical applicability of the isotopic breath test for detection of type 2 diabetes (T2D). Variation of the carbon-13 isotope in human breath depends on the 13C enrichment in the diet taken by subjects. Here, we formulated a new test meal comprising naturally available 13C-enriched foods and subsequently administered it to non-diabetic control (NDC) subjects and those with T2D. We found that the new test meal-derived 13C enrichment of breath CO2 was significantly lower in T2D compared with NDC. Furthermore, from our observations T2D exhibited higher isotopic enrichment of oxygen-18 (18O) in breath CO2 compared with NDC following ingestion of the new meal. We determined the optimal diagnostic cut-off values of 13C (i.e. δ 13C‰ = 7.5‰) and 18O (i.e. Î´ 18O‰ = 3.5‰) isotopes in breath CO2 for precise classification of T2D and NDC. Our new method involving the administration of naturally 13C-abundant nutrients showed a typical diagnostic sensitivity and specificity of about 95%, suggesting a valid and potentially robust global method devoid of any synthetically manufactured commercial 13C-enriched glucose which thus may serve as an alternative diagnostic tool for routine clinical applications.

Bifidobacteria-Insight into clinical outcomes and mechanisms of its probiotic action.

The invasion of pathogens causes a disruption of the gut homeostasis. Innate immune responses and those triggered by endogenous microbiota form the first line of defence in our body. Pathogens often successfully overcome the resistances offered, calling for therapeutic intervention. Conventional strategy involving antibiotics might eradicate pathogens, but often leave the gut uncolonised and susceptible to recurrences. Probiotic supplements are useful alternatives. Bifidobacterium is one of widely studied probiotic genus, effective in restoring gut homeostasis. Mechanisms of probiotic action of bifidobacteria are several, often with strain-specificity. Analysis of streamlined literature reports reveal that although most studies report the probiotic aspect of bifidobacteria, sporadic documented contradictory results exist, challenging its therapeutic application and prompting studies to unambiguously establish the strain-associated probiotic activity and negate adverse effects prior to its clinical administration. Multi-strain/combinatorial therapy possibly relies on a combination of underlying operating mechanisms, each contributing towards enhanced probiotic efficacy, understanding which could help in developing customised formulations against targeted pathogens. Bifidogenic activity is also mediated by surface-associated structural components such as exopolysaccharides, lipoteichoic acids along with metabolites and bifidocins. This highlights scope for developing advanced structural therapeutic strategy which might be pivotal in replacing intact cell probiotics therapy.