Antimony precipitation and removal by antimony hyper resistant strain Achromobacter sp. 25-M.

Microbes have been confirmed to play key role in biogeochemistry of antimony. However, the impact of indigenous bacteria (from active mines) on the behavior of dissolved antimony remained poorly understood. In current study, the hyper antimony-resistant strain, Achromobacter sp. 25-M, isolated from the world largest antimony deposit, Xikuangshan antimony deposit, was evaluated for its role in dissolved Sb(V) and Sb(III) precipitation and removal. Despite of the high resistance to Sb(III) (up to 50 mM), the facultative alkaliphile, 25-M was not capable of Sb(III) oxidation. Meanwhile 25-M can produce high amount of exopolymeric substance (EPS) with the presence of Sb, which prompted us to investigate the potential role of EPS in the precipitation and removal of Sb. To this end, 2 mM of Sb(III) and Sb(V) were added into the experimental systems with and without 25-M to discern the interaction mechanism between microbe and antimony. After 96 hrs' incubation, 88% [1.73 mM (210 mg/L)] of dissolved Sb(V) and 80% [1.57 mM (190 mg/L)] of dissolved Sb(III) were removed. X-ray diffraction and energy dispersive spectroscopy analysis confirmed the formation of valentinite (Sb2O3) in Sb(III) amended system and a solitary Sb(V) mineral mopungite [NaSb(OH)6] in Sb(V) amended group with microbes. Conversely, no precipitate was detected in abiotic systems. Morphologically valentinite was bowtie and mopungite was pseudo-cubic as indicated by scanning electronic microscopy. EPS was subjected to fourier transform infrared (FT-IR) analysis. FT-IR analysis suggested that -OH and -COO groups were responsible for the complexation and ligand exchange with Sb(III) and Sb(V), respectively. Additionally, the C-H group and N-H group could be involved in π-π interaction and chelation with Sb species. All these interactions between Sb and functional groups in EPS may subsequently favore the formation of valentinite and mopungite. Collectively, current results suggested that EPS play fundamental role in bioprecipitation of Sb, which offered a new strategy in Sb bioremediation.

Activating Organic Electrode via Trace Dissolved Organic Molecules.

Organic electrode materials have gained attention for their tunable structures and sustainability, but their low electronic conductivity requires the use of large amounts of carbon additives (30 wt %) and low mass loadings (<2 mg cm-2) in electrodes. Here, we synthesize dibenzo[b,i]phenazine-5,7,12,14-tetrone (DPT) as a cathode active material for an aqueous Zn battery and find that Zn2+ storage dominates the cathode reaction. This battery demonstrates high capacity (367 mAh g-1), high-rate performance, and superlong life (12000 cycles). Remarkably, despite DPT's insulative nature, even with a high mass loading (10 mg cm-2) and only 10 wt % carbon additives, the DPT-based cathode exhibits promising performance due to trace dissolved discharge product (DPTx-). During discharge, the DPT is reduced to trace amounts of dissolved DPTx- at the cathode surface, which in turn reduces the remaining solid DPT as a redox mediator. Furthermore, dissolution-redeposition results in the reduction of DPT size and the formation of pores, further activating the electrode.

Characterization of anti-CD79b/CD3 bispecific antibody, a potential therapy for B cell malignancies.

High rates of relapse and poor prognosis confer an urgent need for novel therapeutic agents for B cell non-Hodgkin lymphomas (B-NHLs). Herein, we describe a human IgG-like anti-CD79b/CD3 bispecific antibody (IBI38D9-L) that selectively depletes antigen-positive malignant B cells as an alternative treatment option for relapsed or refractory NHL patients. The antitumor activity and mechanism of action of IBI38D9-L were investigated in vitro using B-NHL cell lines and human primary effector cells and in vivo using xenograft models reconstituted with human PBMCs (peripheral blood mononuclear cells). Pharmacokinetic (PK) properties and preclinical toxicology were evaluated in cynomolgus monkeys and HSC-NPG mice. IBI38D9-L exerted potent B cell killing as well as T cell activation and proliferation in a tumor cell-dependent manner in vitro and was active against B-NHL cell lines with various CD79b expression levels. Subcutaneous xenograft tumors in NOG mice engrafted with human PBMCs were eradicated by IBI38D9-L treatment. Moreover, IBI38D9-L-treated mice showed a strong infiltration of activated T cells. In HSC-NPG mice, IBI38D9-L resulted in potent B cell depletion in peripheral blood and induced only slight body weight loss and cytokine release syndrome without significant toxicological findings. In cynomolgus monkeys, IBI38D9-L was well tolerated with good pharmacokinetic profiles. Collectively, these preclinical efficacy and safety data provide strong scientific rationales for using anti-CD79b/CD3 bispecific antibody as a promising therapeutic agent for B cell malignancies.

The effect of arteriosclerosis on new-onset renal damage in diabetic patients.

The aim of this study was to investigate the effect of arteriosclerosis on new-onset renal damage in a Chinese community population with diabetes. Patients with diabetes who had attended at least one physical examination after the Brachial-ankle pulse wave velocity (BaPWV) test from 2010 to 2018 were selected as subjects. A total of 4,462 patients were included in the study cohort. BaPWV levels <1,400 cm/s, 1,400-1,799 cm/s, and ≥1,800 cm/s were applied to divide the subjects into a normal arterial stiffness group, borderline atherosclerosis group and atherosclerosis group. Renal damage was defined by isolated proteinuria, isolated eGFR <60 mL/min/1.73 m2, proteinuria and eGFR <60 mL/min/1.73 m2. A Cox proportional risk model was used to analyze the effect of different groups on new-onset renal damage. After a median follow-up of 2.85 (1.88-4.90) years, Cox proportional risk models showed that after adjusting for risk factors, compared with the normal group, the HR and 95% CI of the risk of new-onset renal damage were 1.29 (95% CI: 0.95-1.76) and 1.59 (95% CI: 1.14-2.22) in the borderline atherosclerosis group and the atherosclerosis group, respectively. Atherosclerosis is a risk factor for new-onset renal damage, especially new-onset proteinuria, in diabetic patients.

Boosting Zn Anode Utilization by Trace Iodine Ions in Organic-Water Hybrid Electrolytes through Formation of Anion-rich Adsorbing Layers.

Aqueous Zn batteries are attracting extensive attentions, but their application is still hindered by H2 O-induced Zn-corrosion and hydrogen evolution reactions. Addition of organic solvents into aqueous electrolytes to limit the H2 O activity is a promising solution, but at the cost of greatly reduced Zn anode kinetics. Here we propose a simple strategy for this challenge by adding 50 mM iodine ions into an organic-water (1,2-dimethoxyethane (DME)+water) hybrid electrolyte, which enables the electrolyte simultaneously owns the advantages of low H2 O activity and accelerated Zn kinetics. We demonstrate that the DME breaks the H2 O hydrogen-bond network and exclude H2 O from Zn2+ solvation shell. And the I- is firmly adsorbed on the Zn anode, reducing the Zn2+ de-solvation barrier from 74.33 kJ mol-1 to 32.26 kJ mol-1 and inducing homogeneous nucleation behavior. With such electrolyte, the Zn//Zn symmetric cell exhibits a record high cycling lifetime (14.5 months) and achieves high Zn anode utilization (75.5 %). In particular, the Zn//VS2 @SS full cell with the optimized electrolyte stably cycles for 170 cycles at a low N : P ratio (3.64). Even with the cathode mass-loading of 16.7 mg cm-2 , the full cell maintains the areal capacity of 0.96 mAh cm-2 after 1600 cycles.

Conjugated and Non-conjugated Polymers Containing Two-Electron Redox Dihydrophenazines for Lithium-Organic Batteries.

Organic p-type cathode materials have recently attracted increasing attention due to their higher redox potentials and rate capabilities in comparison to n-type cathodes. However, most of the p-type cathodes based on one-electron redox still suffer from limited stability and low specific capacity (<150 mAh g-1 ). Herein, two polymers, conjugated poly(diethyldihydrophenazine vinylene) (CPP) and non-conjugated poly(diethyldihydrophenazine ethylidene) (NCPP) containing two-electron redox dihydrophenazine, have been developed as p-type cathode materials. It is experimentally and theoretically found that the conjugated linkage among the redox centers in polymer CPP is more favorable for the effective charge delocalization on the conjugated polymer backbone and the sufficient oxidation in the higher potential region (3.3-4.2 V vs. Li/Li+ ). Consequently, the CPP cathode displays a higher reversible specific capacity of 184 mAh g-1 with excellent cycling stability.

Molecular Tailoring of p-type Organics for Zinc Batteries with High Energy Density.

P-type organic electrode materials are known for their high redox voltages and fast kinetics. However, single-electron p-type organic materials generally exhibit low capacity despite high operating voltage and stability, while some multi-electron p-type organic materials have high theoretical capacity but low stability. To address this challenge, we explore the possibility of combining single-electron and multi-electron units to create high-capacity and stable p-type organic electrodes. We demonstrate the design of a new molecule, 4,4'-(10H-phenothiazine-3,7-diyl) bis (N,N-diphenylaniline) (PTZAN), which is created by coupling the triphenylamine molecule and the phenothiazine molecule. The resulting PTZAN||Zn battery shows excellent stability (2000 cycles), high voltage (1.3 V), high capacity (145 mAh g-1 ), and energy density of 187.2 Wh kg-1 . Theoretical calculations and in/ex situ analysis reveal that the charge storage of the PTZAN electrode is mainly driven by the redox of phenothiazine heterocycles and triphenylamine unit, accompanied by the combination/release of anions and Zn2+ .

Predicting the Spatial-Temporal Distribution of Human Brucellosis in Europe Based on Convolutional Long Short-Term Memory Network.

Brucellosis is a chronic infectious disease caused by brucellae or other bacteria directly invading human body. Brucellosis presents the aggregation characteristics and periodic law of infectious diseases in temporal and spatial distribution. Taking major European countries as an example, this study established the temporal and spatial distribution sequence of brucellosis, analyzed the temporal and spatial distribution characteristics of brucellosis, and quantitatively predicted its epidemic law by using different traditional or machine learning models. This paper indicates that the epidemic of brucellosis in major European countries has statistical periodic characteristics, and in the same cycle, brucellosis has the characteristics of piecewise trend. Through the comparison of the prediction results of the three models, it is found that the prediction effect of long short-term memory and convolutional long short-term memory models is better than autoregressive integrated moving average model. The first mock exam using Conv layer and data vectorizations predicted that the convolutional long short-term memory model outperformed the traditional long short-term memory model. Compared with the monthly scale, the prediction of the trend stage of brucellosis can achieve better results under the single model prediction. These findings will help understand the development trend and liquidity characteristics of brucellosis, provide corresponding scientific basis and decision support for potential risk assessment and brucellosis epidemic prevention and control, and reduce the loss of life and property.

Antimony transformation and mobilization from stibnite by an antimonite oxidizing bacterium Bosea sp. AS-1.

Soils and waters are heavily contaminated by antimony in Xikuangshan (XKS) mine area. It is widely accepted that oxidative dissolution of sulfide minerals and aqueous dissolution are the most prevalent geochemical mechanisms for the release of Sb to the environment. Bosea sp. AS-1 is an antimonite-oxidizer isolated from the mine slag in Xikuangshan Sb mine. Whole genome sequencing revealed the presence of multiple sulfur-oxidizing genes, antimony (Sb) metabolism genes and carbon fixation genes in AS-1's genome. We therefore hypothesized that under oxic conditions, AS-1 could mediate the oxidation of sulfide and Sb(III) in stibnite (Sb2S3) and lead to the release of Sb. Indeed, strain AS-1 was discovered as an autotrophic Sb(III)-oxidizer. Antimony mobilization studies conducted with strain AS-1 showed significantly enhanced mobilization of Sb, and complete oxidation of released Sb and sulfur to Sb(V) and sulfate. In addition, AS-1 induced a faster release of Sb under heterotrophic condition, and new acicular minerals might form. These findings support the hypothesis that microorganisms play an important role in the mobilization and transformation of Sb in XKS mine area and may contribute to our further understanding of the Sb biogeochemical redox cycle in natural environment.

Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity.

CD47, an immune checkpoint receptor frequently unregulated in various blood and solid tumors, interacts with ligand SIPRα on innate immune cells, and conveys a "do not eat me" signal to inhibit macrophage-mediated tumor phagocytosis. This makes CD47 a valuable target for cancer immunotherapy. However, the therapeutic utility of CD47-SIRPα blockade monoclonal antibodies is largely compromised due to significant red blood cell (RBCs) toxicities and fast target-mediated clearance as a result of extensive expression of CD47 on normal cells. To overcome these limitations and further improve therapeutic efficacy, we designed IBI322, a CD47/PD-L1 bispecific antibody which attenuated CD47 activity in monovalent binding and blocked PD-L1 activity in bivalent binding. IBI322 selectively bound to CD47+PD-L1+ tumor cells, effectively inhibited CD47-SIRPα signal and triggered strong tumor cell phagocytosis in vitro, but only with minimal impact on CD47 single positive cells such as human RBCs. In addition, as a dual blocker of innate and adaptive immune checkpoints, IBI322 effectively accumulated in PD-L1-positive tumors and demonstrated synergistic activity in inducing complete tumor regression in vivo. Furthermore, IBI322 showed only marginal RBCs depletion and was well tolerated in non-human primates (NHP) after repeated weekly injections, suggesting a sufficient therapeutic window in future clinical development of IBI322 for cancer treatment.

Postoperative Inflammatory Marker Surveillance in Colorectal Peritoneal Carcinomatosis.

BACKGROUND: The prognostic significance of inflammatory markers in solid cancers is well-established, albeit with considerable heterogeneity. This study sought to investigate the postoperative inflammatory marker trend in peritoneal carcinomatosis (PC), with a focus on colorectal PC (CPC), and to propose optimal surveillance periods and cutoffs. METHODS: Data were collected from a prospectively maintained database of PC patients treated at the authors' institution from April 2001 to March 2019. The platelet-lymphocyte ratio (PLR), the neutrophil-lymphocyte ratio (NLR), and the lymphocyte-monocyte ratio (LMR) were collected preoperatively and on postoperative days 0, 1 to 3, 4 to 7, 8 to 21, 22 to 56, and 57 to 90 as averages. Optimal surveillance periods and cutoffs for each marker were determined by maximally selected rank statistics. The Kaplan-Meier method and Cox proportional hazard regression models were used to investigate the association of inflammatory markers with 1-year overall survival (OS) and recurrence-free survival (RFS) using clinicopathologic parameters. RESULTS: The postoperative inflammatory marker trend and levels did not differ between the patients with and those without hyperthermic intraperitoneal chemotherapy (HIPEC). Low postoperative LMR (days 4-7), high postoperative NLR (days 8-21), and high postoperative PLR (days 22-56) were optimal for prognosticating poor 1-year OS, whereas high postoperative PLR and NLR (days 57-90) and low postoperative LMR (days 8-21) were associated with poor 1-year RFS. A composite score of these three markers was prognostic for OS in CPC. CONCLUSIONS: The reported cutoffs should be validated in a larger population of CPC patients. Future studies should account for the inflammatory response profile when selecting appropriate surveillance periods.

Towards High-Performance Zinc-Based Hybrid Supercapacitors via Macropores-Based Charge Storage in Organic Electrolytes.

Zn-based aqueous supercapacitors are attracting extensive attention. However, most of the reported long-life and high-power performances are achieved with low Zn-utilization (<0.6 %) and low mass loading in cathode (<2 mg cm-2 ). And, many obtained high energy densities are generally evaluated without considering the mass of Zn-anode. Herein, we propose a Zn-based hybrid supercapacitor, involving a metal organic framework derived porous carbon cathode, a Zn-anode and an N, N-dimethylformamide (DMF)-based electrolyte containing Zn2+ . We demonstrate that the charge storage of cathode mainly occurs in macropores, showing high rate performance at high mass loading (40 mg cm-2 ). Furthermore, the aprotic nature of electrolyte and formation of Zn2+ -DMF complex avoid the Zn-corrosion and dendrite formation. Therefore, the supercapacitor shows a long-life (9,000 cycles) with a high Zn-utilization (2.2 %). When calculated with the total mass of cathode (40 mg cm-2 ) and Zn-anode, the energy density reaches 25.9 Wh kg-1 .

Molecular Tailoring of an n/p-type Phenothiazine Organic Scaffold for Zinc Batteries.

The p-type or n-type redox reactions of organics are being used as the reversible electrodes to build the next-generation rechargeable batteries with sustainable and tunable characteristics. However, the n-type organics that store cations generally exhibit low potential (<0.8 V vs. Zn/Zn2+ ), while the p-type organics that store anions suffer from limited capacity (<100 mAh g-1 ). Herein, we demonstrate that bis(phenylamino)phenothiazin-5-ium iodide (PTD-1) containing both n-type and p-type redox moieties exhibits a hybrid charge storage mechanism (n/p-type at low potential, p-type at high potential). Such a hybrid mechanism combines the advantages of n- and p-type reactions and compensates for the associated drawbacks of each. Accordingly, the aqueous Zn//PTD-1 full cell shows a high voltage (1.8 Vmaximum or 1.1 Vaverage ), a high capacity 188.24 mAh gPTD-1 -1 (achieved at 40 mA g-1 ), a long-life and a supercapacitor-like high power. These results shed new light on the design of advanced organic electrodes.

A High-Voltage Zn-Organic Battery Using a Nonflammable Organic Electrolyte.

Owing to undesired Zn corrosion and the formation of Zn dendrites in aqueous electrolytes, most of the examples of aqueous Zn batteries with reported excellent performance are achieved with low Zn-utilization (<0.6 %) in the anode and low mass-loading (<3 mg cm-2 ) in the cathode. Herein, we propose a new organic electrolyte for Zn batteries, which contains a zinc trifluoromethanesulfonate (Zn-TFMS) salt and a mixed solvent consisting of propylene carbonate (PC) and triethyl phosphate (TEP). We demonstrate that this electrolyte with an optimized PC/TEP ratio not only exhibits high ionic conductivity and a wide stable potential window, but also facilitates dendrite-free Zn plating/stripping. In particular, the TEP solvent makes the electrolyte nonflammable. Finally, a 2 V Zn//polytriphenylamine composite (PTPAn) battery is fabricated with the optimized electrolyte; it shows a high rate and a long lifetime (2400 cycles) even with a high mass-loading (16 mg cm-2 ) of PTPAn in the cathode and with a high Zn-utilization (3.5 %).

Development and characterization of a novel anti-OX40 antibody for potent immune activation.

With the great success of anti-CTLA-4 and anti-PD-1 therapeutics in cancer immunotherapy, tumor necrosis factor receptor superfamily members have been recognized as ideal targets to provide co-stimulatory signals in combination with immune checkpoint blocking antibodies. Among these is OX40 (CD134), a co-stimulatory molecule expressed by activated immune cells. Recently, several anti-OX40 agonistic monoclonal antibodies, pogalizumab as the most advanced, have entered early phase clinical trials. Using a yeast platform and multiple screening methods, we identified a fully human anti-OX40 antibody (IBI101) with distinct modes of action. Unlike pogalizumab, IBI101 partially blocks the binding of OX40 to its ligand OX40L and exhibits both FcγR-dependent and independent agonistic activities in NF-κB luciferase reporter assays. IBI101 also promotes T cell activation and proliferation in vitro. These unique properties partially explain the more potent anti-tumor activity of IBI101 than that of pogalizumab in humanized NOG mice bearing LoVo tumors. In addition, IBI101 shows efficacious anti-tumor activity in mice when administrated alone or in combination with anti-PD-1 antibodies. In human OX40 knock-in mice bearing MC38 colon carcinoma, IBI101 treatment induces tumor antigen-specific CD8+ T-cell responses, decreases immunosuppressive regulatory T cells in tumor, and enhances the immune response to PD-1 inhibition. Preclinical studies of IBI101 in non-human primates demonstrate typical pharmacokinetic characteristics of an IgG antibody and no drug-related toxicity. Collectively, IBI101 has desirable preclinical attributes which support its clinical development for cancer treatment.

Topographical profiles of macula and optic nerve head in concomitant strabismus patients as measured using OCT and CSLO.

PURPOSE: Investigate morphological changes of macula and optic nerve head (ONH) in concomitant strabismic patients using optical coherence tomography (OCT) and confocal scanning laser ophthalmoscopy (CSLO). METHODS: A cross-sectional study conducted from April 2017 to February 2018 at the Zhongshan Ophthalmic Center, Sun Yat-sen University. Spectral-domain (SD)-OCT and CSLO were used to observe morphological changes of macula and ONH in concomitant strabismic patients with normal vision and healthy controls. In each subject, a 6-mm diameter zone centered at the fovea was scanned and topographical images of the ONH and peripapillary retina were generated. Fundus parameters were recorded and analyzed. RESULTS: A total of 138 cases, including 29 patients with concomitant esotropia (ET), 38 constant exotropia (XT), 42 intermittent exotropia (IXT), and 29 healthy controls, were recruited. Compared with controls, OCT revealed that the thickness of nasal intraretinal layers (IRLs) in ET patients was significantly increased, particularly in ganglion cell layer (GCL) and inner nuclear layer (INL). In XT patients, the temporal half of outer retinal layers (ORLs) showed significant increases in thickness. CSLO findings revealed significant changes in the ONH of ET patients consisting of a thinner retinal nerve fiber layer (RNFL) and a decreased RNFL cross-sectional area, height variation contour, maximum contour depression, and contour line modulation (CLM) temporal-superior area. The nasal-superior cup area and rim volume in XT patients were significantly increased. CONCLUSION: Topographical profiles of the macula and ONH in concomitant strabismic patients with normal vision present with specific regularities.

[Using the FOCUS Family Intervention for Family-Centered Care in a Premature Infant With Grade IV Intraventricular Hemorrhage].

Preterm infants face increased rates of mortality and developmental complications, which are a burden on children's parents (and caregivers), who suffer from exhaustion and situational uncertainty. This case focused on an extremely-low-birth-weight (908 gm) premature infant with initial unstable vital signs complicated by a grade 4 intraventricular hemorrhage (IVH) that led to partial brain atrophy and enlarged brain ventricles. A poor neurological outcome was expected due to the high risk of cerebral palsy and impaired cognitive abilities. Long-term healthcare for this critical infant was causing tremendous physical, emotional, and financial strains on the family. The parents suffered from worries over the poor prognosis, resulting in stress, sleep disorders, and relationship difficulties with the healthcare professionals. Considering the poor prognosis of the infant, the parents faced a medical dilemma between choosing aggressive treatment and withdrawal of treatment, which led to stress and sleep disorders. Differences between the parents and health professionals regarding disease severity perception and treatment opinions further strained their mutual relationship. To ameliorate this issue, the author implemented family-centered care (the FOCUS family intervention) to help the patient and his family. This intervention is designed to increase family involvement, foster an optimistic attitude and effective stress coping techniques, and reduce uncertainty and negative emotions. For the patient, we provided symptom-relief management to improve abnormal muscle tone and development delay. Our intervention ameliorated the negative emotions, insomnia symptoms, and imbalanced family relationships and improved the life quality of the caregivers. Furthermore, the intervention enhanced the patient's autoregulatory ability, and both physical and neurological development. This case study is expected to provide experience in critical care for premature infants with a poor prognosis and their family using a FOCUS family intervention as well as to improve the quality of healthcare delivery in intensive clinical settings.

Zinc-Organic Battery with a Wide Operation-Temperature Window from -70 to 150 °C.

Aqueous zinc (Zn) batteries have been considered as promising candidates for grid-scale energy storage. However, their cycle stability is generally limited by the structure collapse of cathode materials and dendrite formation coupled with undesired hydrogen evolution on the Zn anode. Herein we propose a zinc-organic battery with a phenanthrenequinone macrocyclic trimer (PQ-MCT) cathode, a zinc-foil anode, and a non-aqueous electrolyte of a N,N-dimethylformamide (DMF) solution containing Zn2+ . The non-aqueous nature of the system and the formation of a Zn2+ -DMF complex can efficiently eliminate undesired hydrogen evolution and dendrite growth on the Zn anode, respectively. Furthermore, the organic cathode can store Zn2+ ions through a reversible coordination reaction with fast kinetics. Therefore, this battery can be cycled 20 000 times with negligible capacity fading. Surprisingly, this battery can even be operated in a wide temperature range from -70 to 150 °C.

Cost-Effectiveness Analysis of Humanitarian Hand Surgery Trips According to WHO-CHOICE Thresholds.

PURPOSE: Hand surgery outreach programs to low- and middle-income countries (LMICs) provide much-needed surgical care to the underserved populations and education to local providers for improved care. The cost-effectiveness of these surgical trips has not been studied despite a long history of such efforts. This study aimed to examine the economic impact of hand surgery trips to LMICs using data from the Touching Hands Project and ReSurge International. We hypothesized that hand surgery outreach would be cost-effective in LMICs. METHODS: We analyzed data on the cost of each trip and the surgical procedures performed. Using methods from the World Health Organization (WHO-Choosing Interventions That Are Cost-Effective [WHO-CHOICE]), we determined whether the procedures performed during the outreach trips would be cost-effective. RESULTS: For the 14 hand surgery trips, 378 patients received surgical treatment. Trips varied in the country where interventions were provided, the number of patients served, the severity of the conditions, and the total cost. The cost per disability-adjusted life-year averted ranged from United States (US)$222 to $1,525, all of which were very cost-effective according to WHO-CHOICE thresholds. The cost-effectiveness of global hand surgery was comparable to that of other medical interventions such as multidrug-resistant tuberculosis treatment in similar regions. We also identified a lack of standardized record keeping for these surgical trips. CONCLUSIONS: Hand surgeries performed in LMICs are cost-effective based on WHO-CHOICE criteria. However, a standardized record-keeping method is needed for future research and longitudinal comparison. Understanding the economic impact of hand surgery global outreach is important to the success and sustainability of these efforts, both to allocate resources effectively and to identify areas for improvement. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analysis III.

[6]-Shogaol/ß-CDs inclusion complex: preparation, characterisation, in vivo pharmacokinetics, and in situ intestinal perfusion study.

Aims: The aim was to improve the absorption and bioavailability of [6]-shogaol with ß-cyclodextrin (ß-CD) prior to in vitro and in vivo evaluation. Methods: [6]-Shogaol/ß-CDs inclusion complexes (6-S-ß-CDs) were developed using saturated aqueous solution method and characterised with appropriate techniques. The absorption and bioavailability potential of [6]-shogaol was evaluated via in vivo pharmacokinetics and in situ intestinal perfusion. Results: The results of characterisation showed that 6-S-ß-CDs (drug loading, 7.15%) were successfully formulated. In vitro release study indicated significantly improved [6]-shogaol release. Pharmacokinetic parameters such as Cmax, AUC0-36 h, and oral relative bioavailability (about 685.36%) were substantially enhanced. The in situ intestinal perfusion study revealed that [6]-shogaol was markedly absorbed via passive diffusion in the intestinal segments, and duodenum followed by ileum and jejunum. Conclusions: Cyclodextrin inclusion technology could enhance the intestinal absorption and oral bioavailability of hydrophobic drugs like [6]-shogaol.