Catalytic Activity of the Archetype from Group 4 of the FTR-like Ferredoxin:Thioredoxin Reductase Family Is Regulated by Unique S = 7/2 and S = 1/2 [4Fe-4S] Clusters.

Thioredoxin reductases (TrxR) activate thioredoxins (Trx) that regulate the activity of diverse target proteins essential to prokaryotic and eukaryotic life. However, very little is understood of TrxR/Trx systems and redox control in methanogenic microbes from the domain Archaea (methanogens), for which genomes are abundant with annotations for ferredoxin:thioredoxin reductases [Fdx/thioredoxin reductase (FTR)] from group 4 of the widespread FTR-like family. Only two from the FTR-like family are characterized: the plant-type FTR from group 1 and FDR from group 6. Herein, the group 4 archetype (AFTR) from Methanosarcina acetivorans was characterized to advance understanding of the family and TrxR/Trx systems in methanogens. The modeled structure of AFTR, together with EPR and Mössbauer spectroscopies, supports a catalytic mechanism similar to plant-type FTR and FDR, albeit with important exceptions. EPR spectroscopy of reduced AFTR identified a transient [4Fe-4S]1+ cluster exhibiting a mixture of S = 7/2 and typical S = 1/2 signals, although rare for proteins containing [4Fe-4S] clusters, it is most likely the on-pathway intermediate in the disulfide reduction. Furthermore, an active site histidine equivalent to residues essential for the activity of plant-type FTR and FDR was found dispensable for AFTR. Finally, a unique thioredoxin system was reconstituted from AFTR, ferredoxin, and Trx2 from M. acetivorans, for which specialized target proteins were identified that are essential for growth and other diverse metabolisms.

Regulating Microvascular Free Flaps Reconstruction in "Schobinger Stage 4" Arteriovenous Malformations of Face.

Objectives Arteriovenous malformations (AVMs) are high-flow, aggressive lesions that cause systemic effects and may pose a risk to life. These lesions are difficult to treat as they have a tendency to recur aggressively after excision or embolization. So, it requires a regulating free flap with robust vascular flow averting the postexcisional ischemia-induced collateralization, parasitization, and recruitment of neovessels from the surrounding mesenchyme-a phenomenon precipitating and perpetuating the recurrence of AVM. Materials and Methods Sixteen patients (12 males and 4 females) with AVMs Schobinger type 4 involving face were treated from March 2015 to March 2021 with various free flaps: three free rectus abdominis flaps, one free radial forearm flap, and twelve free anterolateral thigh flaps were used for reconstruction following the wide local excision of Schobinger type 4 facial AVM. The records of these patients were analyzed retrospectively. The average follow-up period was 18.5 months. The functional and aesthetic outcomes were analyzed with institutional assessment scores. Results The average size of the flap harvested was 113.43 cm 2 . Fourteen patients (87.5%) had good-to-excellent score ( p = 0.035) with institutional aesthetic and functional assessment system. The remaining two patients (12.5%) had only fair results. There was no recurrence (0%) in the free flap group versus 64% recurrence in the pedicled flap and skin grafting groups ( p = 0.035). Conclusion Free flaps with their robust and homogenized blood supply provide a good avenue for void filling and an excellent regulating effect in inhibiting any locoregional recurrences of AVMs.

Reconfiguration of Amorphous Complex Oxides: A Route to a Broad Range of Assembly Phenomena, Hybrid Materials, and Novel Functionalities.

Reconfiguration of amorphous complex oxides provides a readily controllable source of stress that can be leveraged in nanoscale assembly to access a broad range of 3D geometries and hybrid materials. An amorphous SrTiO3 layer on a Si:B/Si1- x Gex :B heterostructure is reconfigured at the atomic scale upon heating, exhibiting a change in volume of ≈2% and accompanying biaxial stress. The Si:B/Si1- x Gex :B bilayer is fabricated by molecular beam epitaxy, followed by sputter deposition of SrTiO3 at room temperature. The processes yield a hybrid oxide/semiconductor nanomembrane. Upon release from the substrate, the nanomembrane rolls up and has a curvature determined by the stress in the epitaxially grown Si:B/Si1- x Gex :B heterostructure. Heating to 600 °C leads to a decrease of the radius of curvature consistent with the development of a large compressive biaxial stress during the reconfiguration of SrTiO3 . The control of stresses via post-deposition processing provides a new route to the assembly of complex-oxide-based heterostructures in 3D geometry. The reconfiguration of metastable mechanical stressors enables i) synthesis of various types of strained superlattice structures that cannot be fabricated by direct growth and ii) technologies based on strain engineering of complex oxides via highly scalable lithographic processes and on large-area semiconductor substrates.

Structure and function of an unusual flavodoxin from the domain Archaea.

Flavodoxins, electron transfer proteins essential for diverse metabolisms in microbes from the domain Bacteria, are extensively characterized. Remarkably, although genomic annotations of flavodoxins are widespread in microbes from the domain Archaea, none have been isolated and characterized. Herein is described the structural, biochemical, and physiological characterization of an unusual flavodoxin (FldA) from Methanosarcina acetivorans, an acetate-utilizing methane-producing microbe of the domain Archaea In contrast to all flavodoxins, FldA is homodimeric, markedly less acidic, and stabilizes an anionic semiquinone. The crystal structure reveals an flavin mononucleotide (FMN) binding site unique from all other flavodoxins that provides a rationale for stabilization of the anionic semiquinone and a remarkably low reduction potentials for both the oxidized/semiquinone (-301 mV) and semiquinone/hydroquinone couples (-464 mV). FldA is up-regulated in acetate-grown versus methanol-grown cells and shown here to substitute for ferredoxin in mediating the transfer of low potential electrons from the carbonyl of acetate to the membrane-bound electron transport chain that generates ion gradients driving ATP synthesis. FldA offers potential advantages over ferredoxin by (i) sparing iron for abundant iron-sulfur proteins essential for acetotrophic growth and (ii) resilience to oxidative damage.

Function-Preserving Neurotized Lateral Arm Free Flap in the Reconstruction of Hemiglossectomy Defects.

Introduction and Methods The glabrous, thin, and pliable texture of lateral arm flap with no loss of any axial vessel of the limb renders it a good choice for hemiglossectomy defect reconstruction. The main caveat of this flap harvest is the loss of sensation in the distribution of posterior antebrachial cutaneous nerve (PABCN). In this article, we present two strategic sites and techniques to preserve the integrity of PABCN and at the same time harvesting lateral arm flap with a lengthy lower lateral cutaneous nerve of arm for the neurotization. The outcome of this function-preserving neurotized lateral arm free flap in the reconstruction of hemiglossectomy defects is analyzed and presented in this article. Results Ninety percent of the patients attained grade 3 score in objective assessment, leading to a significant p -value of 0.02 with this technique. All had preservation of sensation in the distribution of PABCN. Conclusion Our technique of harvest and neurotization has brought good functional recovery of the oral cavity with preservation of PABCN.

Methanosarcina acetivorans contains a functional ISC system for iron-sulfur cluster biogenesis.

BACKGROUND: The production of methane by methanogens is dependent on numerous iron-sulfur (Fe-S) cluster proteins; yet, the machinery involved in Fe-S cluster biogenesis in methanogens remains largely unknown. Methanogen genomes encode uncharacterized homologs of the core components of the ISC (IscS and IscU) and SUF (SufBC) Fe-S cluster biogenesis systems found in bacteria and eukaryotes. Methanosarcina acetivorans contains three iscSU and two sufCB gene clusters. Here, we report genetic and biochemical characterization of M. acetivorans iscSU2. RESULTS: Purified IscS2 exhibited pyridoxal 5'- phosphate-dependent release of sulfur from L-cysteine. Incubation of purified IscU2 with IscS2, cysteine, and iron (Fe2+) resulted in the formation of [4Fe-4S] clusters in IscU2. IscU2 transferred a [4Fe-4S] cluster to purified M. acetivorans apo-aconitase. IscU2 also restored the aconitase activity in air-exposed M. acetivorans cell lysate. These biochemical results demonstrate that IscS2 is a cysteine desulfurase and that IscU2 is a Fe-S cluster scaffold. M. acetivorans strain DJL60 deleted of iscSU2 was generated to ascertain the in vivo importance of IscSU2. Strain DJL60 had Fe-S cluster content and growth similar to the parent strain but lower cysteine desulfurase activity. Strain DJL60 also had lower intracellular persulfide content compared to the parent strain when cysteine was an exogenous sulfur source, linking IscSU2 to sulfur metabolism. CONCLUSIONS: This study establishes that M. acetivorans contains functional IscS and IscU, the core components of the ISC Fe-S cluster biogenesis system and provides the first evidence that ISC operates in methanogens.

Toward a mechanistic and physiological understanding of a ferredoxin:disulfide reductase from the domains Archaea and Bacteria.

Disulfide reductases reduce other proteins and are critically important for cellular redox signaling and homeostasis. Methanosarcina acetivorans is a methane-producing microbe from the domain Archaea that produces a ferredoxin:disulfide reductase (FDR) for which the crystal structure has been reported, yet its biochemical mechanism and physiological substrates are unknown. FDR and the extensively characterized plant-type ferredoxin:thioredoxin reductase (FTR) belong to a distinct class of disulfide reductases that contain a unique active-site [4Fe-4S] cluster. The results reported here support a mechanism for FDR similar to that reported for FTR with notable exceptions. Unlike FTR, FDR contains a rubredoxin [1Fe-0S] center postulated to mediate electron transfer from ferredoxin to the active-site [4Fe-4S] cluster. UV-visible, EPR, and Mössbauer spectroscopic data indicated that two-electron reduction of the active-site disulfide in FDR involves a one-electron-reduced [4Fe-4S]1+ intermediate previously hypothesized for FTR. Our results support a role for an active-site tyrosine in FDR that occupies the equivalent position of an essential histidine in the active site of FTR. Of note, one of seven Trxs encoded in the genome (Trx5) and methanoredoxin, a glutaredoxin-like enzyme from M. acetivorans, were reduced by FDR, advancing the physiological understanding of FDR's role in the redox metabolism of methanoarchaea. Finally, bioinformatics analyses show that FDR homologs are widespread in diverse microbes from the domain Bacteria.

Mode of action uncovered for the specific reduction of methane emissions from ruminants by the small molecule 3-nitrooxypropanol.

Ruminants, such as cows, sheep, and goats, predominantly ferment in their rumen plant material to acetate, propionate, butyrate, CO2, and methane. Whereas the short fatty acids are absorbed and metabolized by the animals, the greenhouse gas methane escapes via eructation and breathing of the animals into the atmosphere. Along with the methane, up to 12% of the gross energy content of the feedstock is lost. Therefore, our recent report has raised interest in 3-nitrooxypropanol (3-NOP), which when added to the feed of ruminants in milligram amounts persistently reduces enteric methane emissions from livestock without apparent negative side effects [Hristov AN, et al. (2015) Proc Natl Acad Sci USA 112(34):10663-10668]. We now show with the aid of in silico, in vitro, and in vivo experiments that 3-NOP specifically targets methyl-coenzyme M reductase (MCR). The nickel enzyme, which is only active when its Ni ion is in the +1 oxidation state, catalyzes the methane-forming step in the rumen fermentation. Molecular docking suggested that 3-NOP preferably binds into the active site of MCR in a pose that places its reducible nitrate group in electron transfer distance to Ni(I). With purified MCR, we found that 3-NOP indeed inactivates MCR at micromolar concentrations by oxidation of its active site Ni(I). Concomitantly, the nitrate ester is reduced to nitrite, which also inactivates MCR at micromolar concentrations by oxidation of Ni(I). Using pure cultures, 3-NOP is demonstrated to inhibit growth of methanogenic archaea at concentrations that do not affect the growth of nonmethanogenic bacteria in the rumen.

Non-variceal gastrointestinal bleed in children: surgical experience with emphasis on management challenges.

PURPOSE: This exclusively surgical series on pediatric non-variceal gastrointestinal bleed (NVGIB) defines three levels of bleed site and describes etiology, bleed severity, diagnostic algorithm, and surgical management for each bleed site. Management challenges are detailed. METHODS: Patients aged ≤ 18 years treated surgically for NVGIB were analysed. RESULTS: Bleed site (n = 87) was classified as: upper gastrointestinal bleed (UGIB; n = 11); small bowel bleed (SBB: n = 52); and lower GIB (n = 24). Four etiology-based groups were identified: lesions with ectopic gastric mucosa (EGM; n = 33), tumours (n = 23), ulcers (n = 21), and vascular pathology (n = 8). Bleed severity spectrum was: acute severe bleed (n = 12); subacute overt bleed (n = 59); and occult GIB (n = 16). Preoperative diagnosis was obtained in all UGIB and LGIB lesions. Eighty-two percent of surgical SB lesions were diagnosed preoperatively on Tc99m pertechnetate scan, computed tomography enterography-angiography, and capsule endoscopy; remaining 18% were diagnosed at laparotomy with intra-operative enteroscopy (IOE). Surgical management was tailored to bleed site, severity, and etiology. Indications of IOE and approach to management challenges are detailed. CONCLUSIONS: The commonest site-specific bleed etiologies were duodenal ulcers for UGIB, EGM lesions for SBB, and tumours for LGIB. SBB presented diagnostic challenge. Diagnostic algorithm was tailored to bleed site, age-specific etiology, bleed severity, and associated abdominal/systemic symptoms. Management challenges were acute severe bleed, occult GIB, SBB, obscure GIB, and rare etiologies. IOE has a useful role in SBB management.

Structural and Biochemical Characterizations of Methanoredoxin from Methanosarcina acetivorans, a Glutaredoxin-Like Enzyme with Coenzyme M-Dependent Protein Disulfide Reductase Activity.

Glutaredoxins (GRXs) are thiol-disulfide oxidoreductases abundant in prokaryotes, although little is understood of these enzymes from the domain Archaea. The numerous characterized GRXs from the domain Bacteria utilize a diversity of low-molecular-weight thiols in addition to glutathione as reductants. We report here the biochemical and structural properties of a GRX-like protein named methanoredoxin (MRX) from Methanosarcina acetivorans of the domain Archaea. MRX utilizes coenzyme M (CoMSH) as reductant for insulin disulfide reductase activity, which adds to the diversity of thiol protectants in prokaryotes. Cell-free extracts of M. acetivorans displayed CoMS-SCoM reductase activity that complements the CoMSH-dependent activity of MRX. The crystal structure exhibits a classic thioredoxin-glutaredoxin fold comprising three α-helices surrounding four antiparallel ß-sheets. A pocket on the surface contains a CVWC motif, identifying the active site with architecture similar to GRXs. Although it is a monomer in solution, the crystal lattice has four monomers in a dimer of dimers arrangement. A cadmium ion is found within the active site of each monomer. Two such ions stabilize the N-terminal tails and dimer interfaces. Our modeling studies indicate that CoMSH and glutathione (GSH) bind to the active site of MRX similar to the binding of GSH in GRXs, although there are differences in the amino acid composition of the binding motifs. The results, combined with our bioinformatic analyses, show that MRX represents a class of GRX-like enzymes present in a diversity of methane-producing Archaea.

A Ferredoxin Disulfide Reductase Delivers Electrons to the Methanosarcina barkeri Class III Ribonucleotide Reductase.

Two subtypes of class III anaerobic ribonucleotide reductases (RNRs) studied so far couple the reduction of ribonucleotides to the oxidation of formate, or the oxidation of NADPH via thioredoxin and thioredoxin reductase. Certain methanogenic archaea contain a phylogenetically distinct third subtype of class III RNR, with distinct active-site residues. Here we report the cloning and recombinant expression of the Methanosarcina barkeri class III RNR and show that the electrons required for ribonucleotide reduction can be delivered by a [4Fe-4S] protein ferredoxin disulfide reductase, and a conserved thioredoxin-like protein NrdH present in the RNR operon. The diversity of class III RNRs reflects the diversity of electron carriers used in anaerobic metabolism.

Intercomparison of Aerosol Optical Thickness Derived from MODIS and in Situ Ground Datasets over Jaipur, a Semi-arid Zone in India.

The first detailed seasonal validation has been carried out for the Moderate Resolution Imaging Spectroradiometer (MODIS) Terra and Aqua satellites Level 2.0 Collection Version 5.1 AOT (τMODIS) with Aerosol Robotic Network (AERONET) Level 2.0 AOT (τAERONET) for the years 2009-2012 over semi-arid region Jaipur, northwestern India. The correlation between τMODIS versus τAERONET at 550 nm is determined with different spatial and temporal size windows. The τMODIS overestimates τAERONET within a range of +0.06 ± 0.24 during the pre-monsoon (April-June) season, while it underestimates the τAERONET with -0.04 ± 0.12 and -0.05 ± 0.18 during dry (December-March) and post-monsoon (October-November) seasons, respectively. Correlation without (with) error envelope has been found for pre-monsoon at 0.71 (0.89), post-monsoon at 0.76 (0.94), and dry season at 0.78 (0.95). τMODIS is compared to τAERONET at three more ground AERONET stations in India, i.e., Kanpur, Gual Pahari, and Pune. Furthermore, the performance of MODIS Deep Blue and Aqua AOT550 nm (τDB550 nm and τAqua550 nm) with τAERONET is also evaluated for all considered sites over India along with a U.S. desert site at White Sand, Tularosa Basin, NM. The statistical results reveal that τAqua550 nm performs better over Kanpur and Pune, whereas τDB550 nm performs better over Jaipur, Gual Pahari, and White Sand High Energy Laser Systems Test Facility (HELSTF) (U.S. site).

Elucidating the process of activation of methyl-coenzyme M reductase.

Methyl-coenzyme M reductase (MCR) catalyzes the reversible reduction of methyl-coenzyme M (CH3-S-CoM) and coenzyme B (HS-CoB) to methane and heterodisulfide CoM-S-S-CoB (HDS). MCR contains the hydroporphinoid nickel complex coenzyme F430 in its active site, and the Ni center has to be in its Ni(I) valence state for the enzyme to be active. Until now, no in vitro method that fully converted the inactive MCRsilent-Ni(II) form to the active MCRred1-Ni(I) form has been described. With the potential use of recombinant MCR in the production of biofuels and the need to better understand this enzyme and its activation process, we studied its activation under nonturnover conditions and achieved full MCR activation in the presence of dithiothreitol and protein components A2, an ATP carrier, and A3a. It was found that the presence of HDS promotes the inactivation of MCRred1, which makes it essential that the activation process is isolated from the methane formation assay, which tends to result in minimal activation rates. Component A3a is a multienzyme complex that includes the mcrC gene product, an Fe-protein homolog, an iron-sulfur flavoprotein, and protein components involved in electron bifurcation. A hypothetical model for the cellular activation process of MCR is presented.

Usability of mobile technology to screen for drug-drug interactions in kidney transplant patients.

BACKGROUND AND OBJECTIVES: Kidney transplant recipients are at increased risk for adverse safety events related to reduced renal function and polypharmacy. Health information technology tools have a precautionary role in improving safety in patients with kidney transplants who are at risk of drug-drug interactions. MATERIALS AND METHODS: Usability testing of a drug-drug interaction inquiry system on a convenience sample of kidney transplant patients and their family members was conducted between January and April 2013 by a single interviewer. Each participant was provided with 35 tasks to complete on a cell phone with a manual keypad. The tasks were classified according to how it was completed: easily completed, noncritical error, or critical error (where a participant was unable to complete the given task without intervention by the interviewer). The final task was timed using a stop watch. RESULTS: Out of a total of 16 volunteers, 15 completed the testing. The median time to complete the final task was 4 min (range: 2-9). In a cumulative total of 525 tasks, 33 critical errors were noted. Twelve participants had one or more critical errors. The most frequent critical errors were related to typing and spelling mistakes. Twelve out 15 participants were able to complete the final task without any critical errors. CONCLUSIONS: Understanding transplant patients' preference in technology use and adapting applications to a variety of technological portals will ensure the most effective use of targeted interventions in patient safety, particularly when applied to preventing drug-drug interactions.

Biosynthesis of colloidal gold nanoparticles by Streptomyces sp. NK52 and its anti-lipid peroxidation activity.

Gold nanoparticles (Au-NPs) were synthesized from chloroauric acid using cell free supernatant of Streptomyces sp. NK52 grown in nutrient broth. These nanoparticles were synthesized by varying pH and temperature of the reaction mixture and chloroauric acid concentration. The nanoparticles were characterized by spectrometry, X-ray diffraction, Scanning electron microscopy and energy dispersive spectrometry. Au-NP ranged from 10-100 nm in size and exhibited a polydispersive nature with various shapes like rods, hexagons, triangles, spheres. The diffraction peaks at 2theta = 38.1 degrees and 44.5 degrees could be assigned to the (1 1 1) and (2 0 0) planes of a faced centre cubic (fcc) lattice of gold. Au-NP showed 47% inhibition of lipid peroxidation in vitro. To the best of our knowledge, this is the first report on the rapid biosynthesis of Au-NP using cell free supernatant of Streptomyces sp. and its evaluation for anti-lipid peroxidation.

Dust events and their influence on aerosol optical properties over Jaipur in Northwestern India.

In this study, we systematically document the link between dust episodes and local scale regional aerosol optical properties over Jaipur located in the vicinity of Thar Desert in the northwestern state of Rajasthan. The seasonal variation of AOT(500 nm) (aerosol optical thickness) shows high values (0.51 ± 0.18) during pre-monsoon (dust dominant) season while low values (0.36 ± 0.14) are exhibited during winter. The Ångström wavelength exponent has been found to exhibit low value (<0.25) indicating relative dominance of coarse-mode particles during pre-monsoon season. The AOT increased from 0.36 (Aprilmean) to 0.575 (May-June(mean)). Consequently, volume concentration range increases from April through May-June followed by a sharp decline in July during the first active phase of the monsoon. Significantly high dust storms were observed over Jaipur as indicated by high values of single scattering albedo (SSA(440 nm) = 0.89, SSA(675 nm) = 0.95, SSA870 nm = 0.97, SSA(1,020 nm) = 0.976) than the previously reported values over IGP region sites. The larger SSA values (more scattering aerosol), especially at longer wavelengths, is due to the abundant dust loading, and is attributed to the measurement site's proximity to the Thar Desert. The mean and standard deviation in SSA and asymmetry parameter during pre-monsoon season over Jaipur is 0.938 ± 0.023 and 0.712 ± 0.017 at 675 nm wavelength, respectively. Back-trajectory air mass simulations suggest Thar Desert in northwestern India as the primary source of high aerosols dust loading over Jaipur region as well as contribution by long-range transport from the Arabian Peninsula and Middle East gulf regions, during pre-monsoon season.

BVPaP-3, a T7-like lytic phage of Pseudomonas aeruginosa: its isolation and characterisation.

The increasing emergence of antibiotic-resistant bacteria has produced a growing interest among scientists in bacteriophages as alternative antimicrobial agents. This article reports a lytic phage against an antibiotic-resistant strain of Pseudomonas aeruginosa. Phage BVPaP-3 is a member of the Podoviridae family and morphologically similar to the T7-like phage gh-1. The phage has a hexagonal head of 58-59 nm in diameter and a short tail of 10 × 8 nm. It is stable at a wide range of pH (6-10) and temperatures (4-40°C). Its optimal growth temperature is 37°C and the adsorption rate constant is 1.19 × 10(-9). Latent and eclipse periods are 20 and 15 min, respectively, and the burst size is 44 after 35 min at 37°C. The phage has a DNA size of 41.31 kb and a proteome of 11 proteins. The major protein is 33 kDa in size.

Anatomic placement of the acetabular implant in cementless total hip arthroplasty does not adversely affect the implant survival and patient satisfaction.

Objective: This study aimed to evaluate if the acetabulum's conservative reaming with preservation of the medial acetabular bone and anatomic placement of the acetabular implant in cementless total hip arthroplasty (THA) has any adverse effect on the radiological outcome, long term implant survival and patient satisfaction. Methods: 106 consecutive patients were identified from a single surgeon practice who underwent cementless THA from 2005 to 2010. Twenty-one were lost to follow up, and five patients died unrelated to THA. Eighty patients were available for the study. The mean follow-up was 8.6 years (range 5.7-11.6). The mean age was 61.9 years. Immediate pre- and postoperative radiographs were reviewed to calculate combined offset (Acetabular offset - AO, plus Femoral offset - FO). Implant failure, aseptic loosening, revision surgery, patient satisfaction and complications were assessed on long-term follow-up. Results: Acetabular component survival was 100% with no aseptic failure. None of the patients had revision surgery for any cause. The mean difference in the acetabular offset and combined offset postoperatively was within 3 mm. One patient had a dislocation, and one had a prosthetic joint infection (PJI). 95% of the patients in this series would recommend the hip replacement procedure to others, with a mean satisfaction score of 8.7 (range; 1-10). Conclusion: Conservative acetabular reaming with preservation of medial acetabulum bone with the anatomic placement of the acetabular implant in cementless THA is safe with no adverse effects on implant survival and patient satisfaction. It offers the advantage of preserving the patient's bone stock, which would potentially be of significant advantage to the patient and the surgeon in case of revision arthroplasty.

Strategies to overcome vaccine hesitancy: a systematic review.

BACKGROUND: Vaccination, albeit a necessity in the prevention of infectious diseases, requires appropriate strategies for addressing vaccine hesitancy at an individual and community level. However, there remains a glaring scarcity of available literature in that regard. Therefore, this review aims to scrutinize globally tested interventions to increase the vaccination uptake by addressing vaccine hesitancy at various stages of these interventions across the globe and help policy makers in implementing appropriate strategies to address the issue. METHODS: A systematic review of descriptive and analytic studies was conducted using specific key word searches to identify literature containing information about interventions directed at vaccine hesitancy. The search was done using PubMed, Global Health, and Science Direct databases. Data extraction was based on study characteristics such as author details; study design; and type, duration, and outcome of an intervention. RESULTS: A total of 105 studies were identified of which 33 studies were included in the final review. Community-based interventions, monetary incentives, and technology-based health literacy demonstrated significant improvement in the utilization of immunization services. On the other hand, media-based intervention studies did not bring about a desired change in overcoming vaccine hesitancy. CONCLUSION: This study indicates that the strategies should be based on the need and reasons for vaccine hesitancy for the targeted population. A multidimensional approach involving community members, families, and individuals is required to address this challenging issue.

A comprehensive review on metallic implant biomaterials and their subtractive manufacturing.

There is a tremendous increase in the demand for converting biomaterials into high-quality industrially manufactured human body parts, also known as medical implants. Drug delivery systems, bone plates, screws, cranial, and dental devices are the popular examples of these implants - the potential alternatives for human life survival. However, the processing techniques of an engineered implant largely determine its preciseness, surface characteristics, and interactive ability with the adjacent tissue(s) in a particular biological environment. Moreover, the high cost-effective manufacturing of an implant under tight tolerances remains a challenge. In this regard, several subtractive or additive manufacturing techniques are employed to manufacture patient-specific implants, depending primarily on the required biocompatibility, bioactivity, surface integrity, and fatigue strength. The present paper reviews numerous non-degradable and degradable metallic implant biomaterials such as stainless steel (SS), titanium (Ti)-based, cobalt (Co)-based, nickel-titanium (NiTi), and magnesium (Mg)-based alloys, followed by their processing via traditional turning, drilling, and milling including the high-speed multi-axis CNC machining, and non-traditional  abrasive water jet machining (AWJM), laser beam machining (LBM), ultrasonic machining (USM), and electric discharge machining (EDM) types of subtractive manufacturing techniques. However, the review further funnels down its primary focus on Mg, NiTi, and Ti-based alloys on the basis of the increasing trend of their implant applications in the last decade due to some of their outstanding properties. In the recent years, the incorporation of cryogenic coolant-assisted traditional subtraction of biomaterials has gained researchers' attention due to its sustainability, environment-friendly nature, performance, and superior biocompatible and functional outcomes fitting for medical applications. However, some of the latest studies reported that the medical implant manufacturing requirements could be more remarkably met using the non-traditional subtractive manufacturing approaches. Altogether, cryogenic  machining among the traditional routes and EDM among the non-traditional means along with their variants, were identified as some of the most effective subtractive manufacturing techniques for achieving the dimensionally accurate and biocompatible metallic medical implants with significantly modified surfaces.