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To determine if a reduced secondary operation rate offsets higher implant charges when utilizing suture button fixation for syndesmotic injuries.Retrospective cohort study.Single, urban, Level 1 trauma center.Three-hundred twenty-seven (N=327) skeletally mature patients with rotational ankle fractures (OTA/AO type 44) necessitating concurrent syndesmotic fixation.Suture button or solid 3.5mm screw syndesmotic fixation.To compare implant charges with secondary operation charges based on differential implant removal rates between screws and suture buttons.Patients undergoing screw fixation were older (48.8 vs 39.6 years, p0.01), had more ground level fall mechanisms (59.3% vs 51.1%, p =0.026), and sustained fewer 44C type injuries (34.7% vs 56.8%, p=0.01). Implant removal occurred at a higher rate in the screw fixation group (17.6% vs 5.7%, p=0.005). Binomial logistic regression identified non-smoker status (B=1.03, p=0.04) and implant type (B=1.41, p=0.008) as factors associated with implant removal. Adjusting for age, the NNT with a suture button construct to prevent one implant removal operation was 9, with mean resulting additional implant charges of $9747 ($1083/case). Backwards calculations using data from previous large studies estimated secondary operation charges at approximately $14220, suggesting a potential 31.5% cost savings for suture buttons when considering reduced secondary operation rates.A reduced secondary operation rate may offset increased implant charges for suture button syndesmotic fixation when considering institutional implant removal rates for operations occurring in tertiary care settings. Given these offsetting charges, surgeons should utilize the syndesmotic fixation strategy they deem most appropriate in their practice setting.Economic Level III. See Instructions for Authors for a complete description of levels of evidence.

To determine whether immediate weight bearing after intramedullary fixation of extra-articular proximal tibia fractures (OTA/AO 41A) results in change of alignment before union.Retrospective Review.Level I and Level II Trauma Center.Thirty-seven patients with 37 proximal tibial fractures, all whom could bear weight as tolerated postoperatively. Eighteen fractures were OTA/AO 41-A2, and 19 were OTA/AO 41-A3.Intramedullary nailing of extra-articular proximal tibia fractures.Change in fracture alignment or loss of reduction.The average change in coronal alignment at the final follow-up was 1.22 ± 1.28 degrees of valgus and 1.03 ± 1.05 degrees of extension in the sagittal plane. Twenty-five patients demonstrated excellent initial alignment, 10 patients demonstrated acceptable initial alignment, and 2 patients demonstrated poor initial alignment. Five patients demonstrated a change in alignment from excellent to acceptable at the final follow-up. No patient went from excellent or acceptable initial alignment to poor final alignment. Five patients required unplanned secondary surgical procedures. Two patients required return to the operating room for soft-tissue coverage procedures, 2 patients required surgical debridement of a postoperative infection, and 1 patient underwent debridement and exchange nailing of an infected nonunion. No patient underwent revision for implant failure or loss of reduction.Immediate weight bearing after intramedullary fixation of extra-articular proximal tibia fractures (OTA/AO 41A) led to minimal change in alignment at final postoperative radiographs.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

To determine whether there is a difference in orthopaedic trauma patient medication satisfaction and adherence using an oral versus subcutaneous injectable anticoagulant for venous thromboembolism chemoprophylaxis.Randomized controlled trial.Single academic Level 1 trauma center.One hundred twenty adult orthopaedic trauma patients with operative pelvic or lower extremity fractures were randomized and completed the study.Three weeks of either the service standard 40 mg once daily enoxaparin versus trial medication 10 mg once daily rivaroxaban postoperatively.Patient satisfaction as measured by the Treatment Satisfaction Questionnaire for Medication (TSQM-9). Medication adherence as measured by the Morisky Medication Adherence Scale (MMAS-8).Medication adherence was similar in both groups. Medication satisfaction was significantly higher in the oral rivaroxaban group based on the TSQM-9 and patient-reported data. Secondary outcomes found no significant difference in the incidence of bleeding events or clinically relevant venous thromboembolism. The enoxaparin group experienced more adverse medication-related events. The rivaroxaban medication regimen costs 7.5-10× less out of pocket for uninsured patients.The results of this randomized controlled trial demonstrate that patients with surgical orthopaedic trauma prefer an oral anticoagulant for postoperative venous thromboembolism chemoprophylaxis and suggest that rivaroxaban may be a viable option. Furthermore, large-scale studies are needed to confirm safety and efficacy for rivaroxaban in this population as a potential alternative to enoxaparin and aspirin.Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The aim of this investigation was to develop and analyze a tacrolimus and thymoquinone co-loaded nanostructured lipid carriers (TAC-THQ-NLCs)-based nanogel as a new combinatorial approach for the treatment of psoriasis. The NLCs were formulated by an emulsification-solvent-evaporation technique using glyceryl monostearate, Capryol 90 (oil), and a mixture of Tween 80 and Span 20 as a solid lipid, liquid lipid, and surfactant, respectively. Their combination was optimized using a three-factor and three-level Box–Behnken design (33-BBD). The optimized TAC-THQ-NLCs were observed to be smooth and spherical with a particle size of 144.95 ± 2.80 nm, a polydispersity index of 0.160 ± 0.021, a zeta potential of −29.47 ± 1.9 mV, and an entrapment efficiency of >70% for both drugs. DSC and PXRD studies demonstrated the amorphous state of TAC and THQ in the lipid matrix of the NLCs. An FTIR analysis demonstrated the excellent compatibility of the drugs with the excipients without interactions. The TAC-THQ-NLC-based nanogel (abbreviated as TAC-THQ-NG) exhibited a good texture profile and good spreadability. The in vitro release study demonstrated a sustained drug release for 24 h from the TAC-THQ-NG that followed the Korsmeyer–Peppas kinetic model with a Fickian diffusion mechanism. Moreover, the TAC-THQ-NG revealed significantly higher dose-dependent toxicity against an HaCaT cell line compared to a TAC-THQ suspension gel (abbreviated as TAC-THQ-SG). Furthermore, the developed formulations demonstrated antioxidant activity comparable to free THQ. Confocal microscopy revealed improved permeation depth of the dye-loaded nanogel in the skin compared to the suspension gel. Based on these findings, it was concluded that TAC-THQ-NG is a promising combinatorial treatment approach for psoriasis.

A patient's mental health can have a significant impact on their orthopaedic trauma outcome. It is important for orthopaedic surgeons to identify patients at risk for a poor outcome based on their mental health, to include the presence of post-traumatic stress disorder, depression, and anxiety, among others. Although some behaviors such as catastrophizing have been associated with worse outcomes, others, such as possessing greater self-efficacy have been associated with improved outcomes. Because of the high prevalence of mental health conditions that can have a detrimental effect on outcome, screening should be routinely conducted and at-risk patients referred to appropriate resources in an effort to optimize outcomes.

Plants varyingly serve as control agents for heavy metal loads in environmental compartments, including soils, by accumulating and partitioning most heavy metals in their organs. However, by doing this wonderful job, the plant health and productivity get affected because of the elevated cellular heavy metals. Therefore, exploration of approaches for strengthening plant’s tolerance to cellular heavy metals is very imperative. As an indispensable macronutrient in plants, sulfur (S) is widely known to assist numerous plant functions and is also argued as vital element for various plant metabolic processes both in normal and stressed conditions. However, the discussion on the heavy metal-specific roles of S-containing compounds in plants have been considered least. In this paper, the aspects discussed included the following: (1) heavy metals and their relation with plants; and nutrient-management and S in control of metal stress-impacts in plants are introduced; (2) major insights into S-assimilation and -assimilatory products are overviewed; (3) important roles of assimilatory products in plant tolerance to common heavy metals are highlighted, and (4) metal-specific influence on assimilatory products in plants are discussed.

Black pepper (Piper nigrum L.) is a climbing perennial plant in the Piperaceae family. Pepper has been known since antiquity for its use both as a medicine and a spice. It is particularly valued for its pungency attributed to its principal constituent - piperine. This review summarizes the information on the biological source of piperine, its extraction and isolation strategies, physicochemical properties, and pharmacological activity - analgesic, immunomodulatory, anti-depressive, anti-diarrheal, hepatoprotective, etc. The effect of piperine on biotransformation of co-administered drugs is also presented in this review, along with the mechanisms involved in its bioavailability-enhancing effect. Its important medicinal uses, including anti-hepatotoxic, anti-diarrheal, anti-depressive, analgesic, and immunomodulatory effects, besides many other traditional uses, are compiled. Based on an exhaustive review of literature, it may be concluded that piperine is a very promising alkaloid found in members of the Piperaceae family.

To determine the effectiveness of various types of antibiotic-coated intramedullary implants in the treatment of septic long bone nonunion.Retrospective chart review.Level 1 trauma center.Forty-one patients with septic long bone nonunion treated with an antibiotic cement-coated intramedullary implant.Surgical debridement and placement of a type of antibiotic-coated intramedullary implant.Union and need for reoperation.At an average 27-month follow-up (6-104), 27 patients (66%) had a modified radiographic union score of the tibia of 11.5 or greater, 12 patients (29%) a score lower than 11.5, and 2 patients (5%) underwent subsequent amputation. Six patients underwent no further surgical procedures after the index operation. Patients treated with a rigid, locked antibiotic nail achieved earlier weight-bearing (P = 0.001), less frequently required autograft (P = 0.005), and underwent fewer subsequent procedures (average 0.38 vs. 3.60, P = 0.004) than those treated with flexible core antibiotic rods.Antibiotic-coated intramedullary implants are successful in the treatment of septic nonunions in long bones. In our cohort, rigid, statically locked nails allowed faster rehabilitation, decreased the need for autograft, and decreased the number of additional surgical procedures. Further study is needed to confirm these findings.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host’s body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.

Tuberculosis (TB) is still one of the deadliest disease across the globe caused by Mycobacterium tuberculosis (Mtb). Mtb invades host macrophages and other immune cells, modifies their lysosome trafficking proteins, prevents phagolysosomes formation, and inhibits the TNF receptor-dependent apoptosis in macrophages and monocytes. Tuberculosis (TB) killed 1.4 million people worldwide in the year 2019. Despite the advancements in tuberculosis (TB) treatments, multidrugresistant tuberculosis (MDR-TB) remains a severe threat to human health. The complications are further compounded by the emergence of MDR/XDR strains and the failure of conventional drug regimens to eradicate the resistant bacterial strains. Thus, new therapeutic approaches aim to ensure cure without relapse, to prevent the occurrence of deaths and emergence of drug-resistant strains. In this context, this review article summarises the essential nanotechnology-related research outcomes in the treatment of tuberculosis (TB), including drug-susceptible and drug-resistant strains of Mtb. The novel anti-tuberculosis drug delivery systems are also being detailed. This article highlights recent advances in tuberculosis (TB) treatments, including the use of novel drug delivery technologies such as solid lipid nanoparticles, liposomes, polymeric micelles, nano-suspensions, nano-emulsion, niosomes, liposomes, polymeric nanoparticles and microparticles for the delivery of anti-TB drugs and hence eradication and control of both drug-susceptible as well as drug-resistant strains of Mtb.

Aims Physician burnout and its consequences have been recognized as increasingly prevalent and important issues for both organizations and individuals involved in healthcare delivery. The purpose of this study was to describe and compare the patterns of self-reported wellness in orthopaedic surgeons and trainees from multiple nations with varying health systems. Methods A cross-sectional survey of 774 orthopaedic surgeons and trainees in five countries (Australia, Canada, New Zealand, UK, and USA) was conducted in 2019. Respondents were asked to complete the Mayo Clinic Well-Being Index and the Stanford Professional Fulfillment Index in addition to 31 personal/demographic questions and 27 employment-related questions via an anonymous online survey. Results A total of 684 participants from five countries (Australia (n = 74), Canada (n = 90), New Zealand (n = 69), UK (n = 105), and USA (n = 346)) completed both of the risk assessment questionnaires (Mayo and Stanford). Of these, 42.8% (n = 293) were trainees and 57.2% (n = 391) were attending surgeons. On the Mayo Clinic Well-Being Index, 58.6% of the overall sample reported feeling burned out (n = 401). Significant differences were found between nations with regards to the proportion categorized as being at risk for poor outcomes (27.5% for New Zealand (19/69) vs 54.4% for Canada (49/90) ; p = 0.001). On the Stanford Professional Fulfillment Index, 38.9% of the respondents were classified as being burned out (266/684). Prevalence of burnout ranged from 27% for Australia (20/74 up to 47.8% for Canadian respondents (43/90; p = 0.010). Younger age groups (20 to 29: RR 2.52 (95% confidence interval (CI) 1.39 to 4.58; p = 0.002); 30 to 39: RR 2.40 (95% CI 1.36 to 4.24; p = 0.003); 40 to 49: RR 2.30 (95% CI 1.35 to 3.9; p = 0.002)) and trainee status (RR 1.53 (95% CI 1.15 to 2.03 p = 0.004)) were independently associated with increased relative risk of having a ‘at-risk’ or ‘burnout’ score. Conclusions The rate of self-reported burnout and risk for poor outcomes among orthopaedic surgeons and trainees varies between countries but remains unacceptably high throughout. Both individual and health system characteristics contribute to physician wellness and should be considered in the development of strategies to improve surgeon wellbeing. Level of Evidence: III Cite this article: Bone Jt Open 2021;2(11):932–939.

Vincristine, one of the major vinca alkaloid of Catharanthus roseus (L.) G. Don. (Apocynaceae), was enhanced under in vitro callus culture of C. roseus using fungal extract of an endophyte Alternaria sesami isolated from the surface-sterilized root cuttings of C. roseus. Vindoline, a precursor molecule for vincristine production, was detected for the first time in the fungal endophyte A. sesami which was used as a biotic elicitor in this study to enhance vincristine content in the C. roseus callus. It was identified using high-performance liquid chromatography and mass spectroscopy techniques by matching retention time and mass data with reference molecule. Supplementing the heat sterilized A. sesami endophytic fungal culture extract into the callus culture medium of C. roseus resulted in the enhancement of vincristine content in C. roseus callus by 21.717% after 105-day culture.

OBJECTIVES To review a large, multicenter experience to identify the current salvage and amputation rates of these combined injuries and, where possible, the variables that predict amputation. DESIGN Retrospective. SETTING Nine trauma centers. PATIENTS This study involved 199 patients presenting to 9 trauma centers with orthopaedic and vascular injuries resulting in ischemic limbs for whom the orthopaedic service was involved with the decision for salvage versus amputation. RESULTS We reviewed 199 patients, 17-85 years of age. One hundred seventy-two of the injuries were open. Thirty-eight patients (19%) were treated with amputation upon admission as they were deemed to be unsalvageable. Of the remaining 161 patients who had attempted salvage, 36 (30%) required late amputation. Closed injuries were successfully salvaged in 25 of 27 cases (93%). The highest rate of amputation was in tibia fractures with a combined amputation rate of 62%. In those attempted to be salvaged, 21 of 48 (44%) required amputation. The ischemia time for successful salvage was significantly less, P = 0.03. One hundred twenty-four patients had their definitive vascular repair before the bony reconstruction. There were 15 vascular complications, of which 13 (86%) had the definitive vascular repair performed before the definitive osseous repair, although this was not statistically significant. CONCLUSIONS In this series of combined orthopaedic and vascular injuries, we found a high rate of acute and late amputations. It is possible that other protocols, such as shunting and stabilizing the osseous injury, before vascular repair may benefit limb salvage, although this needs more study. LEVEL OF EVIDENCE Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Objectives To evaluate a large series of open fractures of the forearm following gunshot wounds in order to determine complication rates and factors that may lead to infection, nonunion, or compartment syndrome. Design Multi-center retrospective review. Setting Nine Level 1 Trauma CentersPatients/Participants: 168 patients had 198 radius and ulna fractures due to firearm injuries. All patients were adults, had a fracture due to a firearm injury and at least one year clinical follow-up or follow-up until union. Average follow-up was 831 days. Intervention Most patients (91%) received antibiotics. Formal irrigation and debridement in the operating room was performed in 75% of cases along with either internal fixation (75%), external fixation (6%), or I&D without fixation (19%). Main outcome measures Complications including neurovascular injuries, compartment syndrome, infection and nonunion. Results Twenty-one percent of patients had arterial injuries and 40% had nerve injuries. Nine patients (5%) developed compartment syndrome. Seventeen patients (10%) developed infections, all in comminuted or segmental fractures. Antibiotics were not associated with a decreased risk of infection. Infections in the ulna were more common in fractures with retained bullet fragments and bone loss. Twenty patients (12%) developed a nonunion. Nonunions were associated with high velocity firearms and bone defect size. Conclusions Open fractures of the forearm from gunshot wounds are serious injuries that carry high rates of nonunion and infection. Fractures with significant bone defects are at increased risk of nonunion and should be treated with stable fixation and proper soft tissue handling. Ulna fractures are at particularly high risk for deep infection and septic nonunion and should be treated aggressively. Forearm fractures from gunshot wounds should be followed until union to identify long term complications. Level of evidence Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

This study aimed to test the role of hydrogen sulfide (H2S) in the responses regarding the nitric oxide- (NO) and sulfur (S)-mediated improvement in photosynthesis and growth under cadmium (Cd) stress in mustard (Brassica juncea L. cv. Giriraj), and integrate the mechanisms of S, nitrogen (N), and antioxidant metabolism. The plants grown with Cd (200 mg Cd kg−1 soil) exhibited reduced assimilation of S and N and diminished photosynthetic performance, which was associated with higher Cd accumulation-induced excess reactive oxygen species (ROS) production. The application of 100 μM of sodium nitroprusside (SNP, a NO donor) together with a more prominent concentration of S resulted in increased photosynthetic S- and N-use efficiency, production of non-protein thiols and phytochelatins, efficiency of enzymatic (superoxide dismutase, ascorbate peroxidase, and glutathione reductase), non-enzymatic antioxidants (ascorbate and glutathione) limiting Cd accumulation and, thus, reduced oxidative stress (superoxide radical, hydrogen peroxide, and thiobarbituric acid reactive species content). The benefit of NO together with S was manifested through a modulation in H2S production. The use of 100 μM of hypotaurine (HT; H2S scavenger) or 100 μM of cPTIO (2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) in plants treated with NO plus S reversed the action of NO plus S, with a higher reduction in photosynthesis and growth with the use of HT, suggesting that H2S plays a significant role in the NO- and S-mediated alleviation of Cd stress. The interplay of NO and ES with H2S may be used in augmenting the photosynthesis and growth of Cd-grown mustard plants.

Phytohormones have a role in stress adaptation. The major mechanism underlying the role of exogenously-sourced nitric oxide (NO; as sodium nitroprusside, SNP: 50.0 µM) and salicylic acid (SA; 0.5 mM) in the presence of 2.0 mM SO4−2 was assessed in heat stress (HS; 40 °C for 6 h daily for 15 days) tolerance in wheat (Triticum aestivum L. cv. HD-3226). The cultivar HD-3226 possessed high photosynthetic sulfur use efficiency (p-SUE) among the six cultivars screened. Plants grown under HS exhibited an increased content of reactive oxygen species (ROS; including superoxide radical and hydrogen peroxide) and extent of lipid peroxidation with a consequent reduction in photosynthesis and growth. However, both NO and SA were found to be protective against HS via enhanced S assimilation. Their application reduced oxidative stress and increased the activity of antioxidant enzymes. NO or SA supplementation along with S under HS recovered the losses and improved photosynthesis and growth. The use of SA inhibitor (2-aminoindane-2-phosphonic acid; AIP) and NO scavenger (cPTIO) confirmed that the mitigating effects of SA and NO involved induction in S assimilation.

The involvement of melatonin in the regulation of salt stress acclimation has been shown in plants in this present work. We found that the GOAL cultivar of wheat (Triticum aestivum L.) was the most salt-tolerant among the investigated cultivars, GOAL, HD-2967, PBW-17, PBW-343, PBW-550, and WH-1105 when screened for tolerance to 100 mM NaCl. The application of 100 μM melatonin maximally reduced oxidative stress and improved photosynthesis in the cv. GOAL. Melatonin supplementation reduced salt stress-induced oxidative stress by upregulating the activity of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR), and reduced the glutathione (GSH) production. This resulted in increased membrane stability, photosynthetic-N use efficiency and photosynthesis in plants. The application of 50 μM of the ethylene biosynthesis inhibitor aminoethoxyvinylglycine (AVG) in the presence of melatonin and salt stress increased H