Accuracy of the Application of 3-Dimensional Printing Models in Orbital Blowout Fractures-A Preliminary Study.

BACKGROUND: Application of 3-dimensional (3D) printing technology has grown in the medical field over the past 2 decades. In managing orbital blowout fractures, 3D printed models can be used as intraoperative navigators and could shorten the operational time by facilitating prebending or shaping of the mesh preoperatively. However, a comparison of the accuracy of computed tomography (CT) images and printed 3D models is lacking. MATERIAL AND METHODS: This is a single-center retrospective study. Patients with unilateral orbital blowout fracture and signed up for customized 3D printing model were included. Reference points for the 2D distance were defined (intersupraorbital notch distance, transverse horizontal, sagittal vertical, and anteroposterior axes for orbital cavity) and measured directly on 3D printing models and on corresponding CT images. The difference and correlation analysis were conducted. RESULTS: In total, 9 patients were reviewed from June 2017 to December 2020. The mean difference in the intersupraorbital notch measurement between the 2 modules was -0.14 mm (P = 0.67). The mean difference in the distance measured from the modules in the horizontal, vertical, and anteroposterior axes of the traumatic orbits was 0.06 mm (P = 0.85), -0.23 mm (P = 0.47), and 0.51 mm (P = 0.32), whereas that of the unaffected orbits was 0.16 mm (P = 0.44), 0.34 mm (P = 0.24), and 0.1 mm (P = 0.88), respectively. Although 2D parameter differences (<1 mm) between 3D printing models and CT images were discovered, they were not statistically significant. CONCLUSIONS: Three-dimensional printing models showed high identity and correlation to CT image. Therefore, personalized models might be a reliable tool of virtual surgery or as a guide in realistic surgical scenarios for orbital blowout fractures.

Printing a Three-Dimensional Patient-Specific Safety Device for Reducing the Potential Risk of Mental Nerve Injury During Transoral Thyroidectomy.

BACKGROUND: Thyroidectomy transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe and cosmetically appealing alternative for well-selected patients undergoing thyroidectomy. However, during TOETVA, placement of the two lateral trocars and/or manipulation of the surgical instruments through the trocars may potentially injure and/or compress the mental nerve (MN) because the actual location of the nerve foramen may vary among individuals. The MN injury rate was reported to be as high as 75% in the initial period of robotic-assisted TOETVA. To reduce the potential risk of MN injury, we implemented a three-dimensional printing technology to develop a safety device for TOETVA. METHODS: The patient-specific safety device (PSSD) was a brace with an exact fit to the lower teeth and two safety markers on each side to indicate the location of the mental foramen. For patient in whom the brace would not be applicable, a 3D mandibular model was printed as a PSSD instead. We analyzed 66 patients undergoing TOETVA at our institution from March 2017 to March 2019. The preoperative details and complication profiles were also analyzed. RESULTS: With incorporation of the PSSD into our TOETVA procedure, there have been no cases of MN injury. CONCLUSIONS: Our own TOETVA series has demonstrated that the implementation of the PSSD has been successful in preoperatively identifying and preventing the potential risk of MN injury. Although the additional requirements of preoperative CT and time for fabricating the device impose limitations, the influence of the PSSD in TOETVA is positive.

Sphingosine-1-phosphate in Endothelial Cell Recellularization Improves Patency and Endothelialization of Decellularized Vascular Grafts In Vivo.

BACKGROUND: S1P has been shown to improve the endothelialization of decellularized vascular grafts in vitro. Here, we evaluated the potential of tissue-engineered vascular grafts (TEVGs) constructed by ECs and S1P on decellularized vascular scaffolds in a rat model. METHODS: Rat aorta was decellularized mainly by 0.1% SDS and characterized by histology. Rat ECs, were seeded onto decellularized scaffolds, and the viability of the ECs was evaluated by biochemical assays. Then, we investigated the in vivo patency rate and endothelialization for five groups of decellularized vascular grafts (each n = 6) in a rat abdominal aorta model for 14 days. The five groups included (1) rat allogenic aorta (RAA); (2) decellularized RAA (DRAA); (3) DRAA with S1P (DRAA/S1P); (4) DRAA with EC recellularization (DRAA/EC); and (5) DRAA with S1P and EC recellularization (DRAA/EC/S1P). RESULTS: In vitro, ECs were identified by the uptake of Dil-Ac-LDL. S1P enhanced the expression of syndecan-1 on ECs and supported the proliferation of ECs on decellularized vascular grafts. In vivo, RAA and DRAA/EC/S1P both had 100% patency without thrombus formation within 14 days. Better endothelialization, more wall structure maintenance and less inflammation were noted in the DRAA/EC/S1P group. In contrast, there was thrombus formation in the DRAA, DRAA/S1P and DRAA/EC groups. CONCLUSION: S1P could inhibit thrombus formation to improve the patency rate of EC-covered decellularized vascular grafts in vivo and may play an important role in the construction of TEVGs.

Cognition-Modulated Frontal Activity in Prediction and Augmentation of Antidepressant Efficacy: A Randomized Controlled Pilot Study.

Higher rostral anterior cingulate cortex (rACC) activity correlated with frontal theta power (frontalθ) is associated with better antidepressant responses. The antidepressant efficacy of repetitive transcranial magnetic stimulation (rTMS) varied widely; however, the effects of TMS might be modulated by manipulating the pretreatment neural states. Therefore, we conducted a pilot study to investigate whether manipulated frontalθ before rTMS treatment could predict and augment antidepressant responses. A computerized rACC-engaging cognitive task (RECT) was exploited continuously for 10 min to patients with major depressive disorder. In total, 36 patients were randomized to 3 groups (Group-A: RECT[active] + rTMS[active]; Group-B: RECT[sham] + rTMS[active]; Group-C: RECT[active] + rTMS[sham]). Frontalθ and whole-brain glucose uptakes were assessed. We found that the RECT-modulated increases in frontalθ correlated well with rACC glucose uptakes. The treatment responders demonstrated a significant increase in frontalθ after RECT. Post-RECT frontalθ had good sensitivity/specificity in predicting antidepressant responses to rTMS. Group-A had more reduction in total depression scores, had more responders, and was more likely to achieve remission than other groups (Group-A [41.6%] > Group-B [16.6%] > Group-C [0%], P < 0.05). A significant enhancement in the post-1st-rTMS frontalθ was observed in Group-A responders but not in Group-B responders, supporting the argument that RECT-modulated rTMS augmented rTMS efficacy. In conclusion, this study suggests that manipulating pre-rTMS neural activity could predict and augment antidepressant effects to rTMS treatment.

Prefrontal glucose metabolism in medication-resistant major depression.

BACKGROUND: Medication-resistant depression (MRD) is associated with poorer attentional performance and immense socioeconomic costs. AIMS: We aimed to investigate the central pathophysiology of MRD, previously linked to impaired prefrontal cortex function. METHOD: A total of 54 participants (22 with MRD, 16 with non-resistant depression, 16 healthy controls) were recruited. Non-MRD status was confirmed by a prospective 6-week antidepressant trial. All medication-free participants underwent a go/no-go task to study prefrontal cortical function (attention) and positron emission tomography scans to study regional cerebral glucose metabolism (rCMglu) at rest. RESULTS: The MRD group had worse attentional ratings and decreased rCMglu compared with the non-MRD and control groups. Attentional performance was positively associated with prefrontal cortex rCMglu. The prefrontal cortex differences between MRD and non-MRD groups remained after adjusting for past depressive episodes (F(1,35) = 4.154, P = 0.043). CONCLUSIONS: Pronounced hypofrontality, with the associated attentional deficits, has a key role in the neuropathology of medication-resistant depression.

Functional dysconnection in the prefrontal-amygdala circuitry in unaffected siblings of patients with bipolar I disorder.

OBJECTIVES: Bipolar I disorder (BD) is a highly heritable disorder characterized by mood swings between high-energy and low-energy states. Amygdala hyperactivity and cortical inhibitory hypoactivity [e.g., of the dorsolateral prefrontal cortex (dlPFC)] have been found in patients with BD, as evidenced by their abnormal resting-state functional connectivity (FC) and glucose utilization (GU). However, it has not been determined whether functional abnormalities of the dlPFC-amygdala circuit exist in unaffected, healthy siblings of the patients with BD (BDsib). METHODS: Twenty euthymic patients with BD, 20 unaffected matching BDsib of the patient group, and 20 well-matched healthy control subjects were recruited. We investigated seed-based FC (seeds: dlPFC) with resting-state functional magnetic resonance imaging and GU in the regions of interest (e.g., dlPFC and amygdala) using (18) F-fluorodeoxyglucose positron emission tomography. RESULTS: The FC in the dlPFC (right)-amygdala circuit was statistically abnormal in patients with BD and BDsib, but only the patients with BD demonstrated hypoactive GU bilaterally in the dlPFC and hyperactive GU bilaterally in the amygdala. Facilitating differentiation between the BD groups, the altered FC between dlPFC (right) and amygdala (left) was even more prominent in the patients with BD (p < 0.05). CONCLUSIONS: There was a dysfunctional connection with intact GU in the dlPFC-amygdala circuit of the BDsib, which highlights the vulnerability in families with BD. Diminished top-down control from the bilateral dlPFC, which prevents adequate inhibition of limbic hyperactivity, might mediate the development of BD.

Association of thalamic serotonin transporter and interleukin-10 in bipolar I disorder: a SPECT study.

OBJECTIVES: The serotonin hypothesis plays a critical role in the etiology of bipolar disorder (BD). Although many studies have demonstrated reciprocal relationships between serotonin metabolism and immune-inflammatory pathways that occur in depression, studies linking serotonergic function and cytokines are still limited concerning BD. The aim of this study was to investigate the interaction of brain serotonin transporter (SERT) and cytokines in BD. METHODS: Twenty patients with euthymic BD and 20 age- and sex-matched healthy controls (HC) were recruited. Single photon emission computed tomography with the radiotracer (123) I-ADAM was used for the SERT imaging. The specific uptake ratio, which represents SERT availability, was the primary measured outcome. Cytokines included the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory cytokine interleukin-10 (IL-10). Cytokine concentration was measured using an enzyme-linked immunosorbent assay. RESULTS: SERT availability was significantly lower in the midbrain and caudate of patients with BD compared with HC, but not in the thalamus and putamen. IL-10 was significantly higher, whereas TNF-α was not different in euthymic patients with BD compared with HC. There was a significant association of SERT availability and IL-10 in the thalamus, but not in the midbrain, caudate, or putamen. CONCLUSIONS: Our results demonstrate the interaction of SERT availability and IL-10 in euthymic BD. This result may further explain the role of SERT and cytokines in the etiology of BD.

A newly designed total implantable venous access device in rats for research with high efficiency and low cost.

BACKGROUND: In this study, we introduced a newly designed totally implantable device for long-term vascular access in rats and compared its efficacy, related complications, and cost-effectiveness with conventional exteriorized jugular vein catheters. METHODS: Forty adult male Sprague-Dawley rats, weighing 250-300 g, were equally divided into two groups (I and II) and all underwent jugular vein catheterization surgery. The totally implanted device was used in group I and conventional exteriorized catheters were used in group II. The functionality of each catheter was checked every 3 d and evaluation included vascular accessibility, patency, and infection. The weight of the animal and microbial culture from the wound and tube were also monitored. We analyzed the cause of vascular access failure and complications, both mechanical and infectious, and compared related variables. RESULTS: The proportions of 9-d patency and 30-d patency in group I were 90% (18/20) and 75% (15/20), respectively, and in group II 80% (16/20) and 35% (7/20), respectively. There was a statistically significant difference in 30-d patency. The rats in group II were more liable to involve vascular access failure because of catheter dislodgment and had a higher infection rate (P = 0.001). Daily body weight gain was also greater in group I than in group II (2.46 ± 0.59 g/d versus 1.84 ± 0.96 g/d; P = 0.02). CONCLUSIONS: This newly designed and totally implanted device substantially increases the success rate of long-term venous access compared with conventional methods. It reinforces the merits of the subcutaneous port and a tethered swivel system and overall has better performance and reliability. Furthermore, given its low cost and the high level of effectiveness offered, this technology could be a powerful tool to be used in future translational medicine research, especially in cases of long-term intravascular administration.

Association of brain serotonin transporter availability and brain-derived neurotrophic factor in models of serotonin transporter genotypes in healthy subjects.

The S-allele of functional polymorphisms of the serotonin transporter (SERT) gene has been demonstrated to have lower transcriptional activity compared with the L-allele, which shows low expression of SERT in the brain. However, this finding cannot be consistently replicated in vivo. The aim of this study was to determine the availability of SERT based on SERT genotype. We also examined the relationship between brain-derived neurotrophic factor (BDNF) and the availability of SERT. Sixty-two healthy subjects were recruited. Each subject underwent single-photon emission computed tomography with I-ADAM (I-labeled 2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) for imaging SERT in the brain. The specific uptake ratio was measured, and venous blood was drawn when the subject underwent single-photon emission computed tomography to evaluate BDNF levels and SERT genotype. All subjects expressed SERT genotypes that were consistent with a biallelic model, and 26 subjects had SERT genotypes that were consistent with a triallelic model. No differences in specific uptake ratio were detected in the midbrain, putamen, caudate, and thalamus based on the SERT genotype using the biallelic and triallelic models. Interestingly, The Pearson correlation coefficient revealed a positive correlation between BDNF and SERT availability. In particular, this relationship was observed in homozygous S-allele expression and a genotype with low functional expression (SaSa/SaLg) in the biallelic and triallelic models of SERT genotypes, respectively. This finding might explain why the SS genotype of SERT did not increase the risk of major depressive disorder in Asian populations and implicate an important role of BDNF in the patients, who has the SS genotype of the SERT gene.

Synthesis and biological evaluation of technetium-99m labeled galactose derivatives as potential asialoglycoprotein receptor probes in a hepatic fibrosis mouse model.

Two galactose derivatives, a monovalent (99m)Tc-MAMA-MGal galactoside and a divalent (99m)Tc-MAMA-DGal galactoside, were synthesized and radiolabeled in high radiochemical purity (>98%). Dynamic microSPECT imaging and biodistribution study of two traces in normal and liver fibrosis mice showed that the (99m)Tc-MAMA-DGal revealed higher specific binding to asialoglycoprotein receptors in liver and then rapidly excreted via both hepatobiliary system and renal clearance. The results suggest that (99m)Tc-MAMA-DGal may be used as SPECT probes for noninvasive evaluation of asialoglycoprotein receptor-related liver dysfunction.

Differential relations between fronto-limbic metabolism and executive function in patients with remitted bipolar I and bipolar II disorder.

OBJECTIVES: The aim of this study was to investigate the relationship between resting brain glucose metabolism and cognitive profiles in patients with remitted bipolar I disorder (BD-I) and bipolar II disorder (BD-II). We hypothesized that BD-I patients (compared to BD-II patients) would perform worse on tests of cognitive function because of abnormal metabolism in the prefrontal cortex and other mood-related brain areas. METHODS: Thirty-four patients with remitted bipolar disorder (BD) (BD-I = 17, BD-II = 17) under treatment and 17 well-matched healthy controls received both fluorodeoxyglucose ((18) F-FDG) positron emission tomography (PET) and neuropsychological tests of attention, memory, and executive function. RESULTS: Clinical features in patients with BD-I and BD-II were comparable. Executive function, as indicated by performance on the Wisconsin Card Sorting Test, was significantly worse (i.e., higher percentage of errors, lower percentage of conceptual level responses, and fewer categories completed) in BD-I patients than in BD-II patients and healthy subjects. No difference in attention and memory tests was found among these three groups. Brain PET analysis showed that BD-I patients (compared to BD-II patients) had significantly lower glucose uptake in the bilateral anterior cingulum, insula, striatum, and part of the prefrontal cortex, and higher glucose uptake in the left parahippocampus. Further analyses revealed significant correlations between poor executive function and abnormal glucose uptake in other brain areas in BD-I patients. CONCLUSIONS: There are neurobiological differences between subtypes of BD. BD-I is associated with more impaired fronto-limbic circuitry, which might account for reduced executive function in BD-I patients during remission.

Short term vs. long term test-retest reproducibility of ¹²³I-ADAM for the binding of serotonin transporters in the human brain.

Previous brain imaging studies have demonstrated a seasonal difference of serotonin transporter (SERT) binding in the human brain. However, the results were somewhat contradictory. We conducted test-retest study with single photon emission computed tomography (SPECT) with ¹²³I-ADAM as ligand in 28 healthy subjects. Ten of the subjects were studied within 1 month, whereas 18 were randomly assigned to be studied over a period of up to 1 year. The primary measure was the specific uptake ratio (SUR). Regions of interest included the midbrain, thalamus, putamen and caudate. The intra-class correlation coefficient (ICC) was 0.52-0.94 across different brain regions over 1 month, whereas the ICC was -0.24-0.63 over a 1-year period. The 1-month variability ranged from 6.5 ± 5.1% to 12.5 ± 10.6% across different brain regions, and the 1-year variability ranged from 16.5 ± 9.6% to 41.9 ± 35.5%. The Kruskal-Wallis test revealed a significant difference of variability across months. The Wilcoxon Signed Ranks Test showed the SUR between test-retest scans was of borderline significance. Curve fitting, using a 4th degree polynomial model, revealed a significant circadian correlation between the variability and interval of test-retest measurements. Our findings demonstrate the test-retest reproducibility of ¹²³I-ADAM in different time periods and suggest that circadian variation of SERT levels in the human brain might exist.

Striatal dopamine transporter binding for predicting the development of delayed neuropsychological sequelae in suicide attempters by carbon monoxide poisoning: A SPECT study.

Carbon monoxide poisoning (COP) after charcoal burning results in delayed neuropsychological sequelae (DNS), which show clinical resemblance to Parkinson's disease, without adequate predictors at present. This study examined the role of dopamine transporter (DAT) binding for the prediction of DNS. Twenty-seven suicide attempters with COP were recruited. Seven of them developed DNS, while the remainder did not. The striatal DAT binding was measured by single photon emission computed tomography with (99m)Tc-TRODAT. The specific uptake ratio was derived based on a ratio equilibrium model. Using a logistic regression model, multiple clinical variables were examined as potential predictors for DNS. COP patients with DNS had a lower binding on left striatal DAT binding than patients without DNS. Logistic regression analysis showed that a combination of initial loss of consciousness and lower left striatal DAT binding predicted the development of DNS. Our data indicate that the left striatal DAT binding could help to predict the development of DNS. This finding not only demonstrates the feasibility of brain imaging techniques for predicting the development of DNS but will also help clinicians to improve the quality of care for COP patients.

Preoperative positron emission tomography/computed tomography predicts advanced lymph node metastasis in esophageal squamous cell carcinoma patients.

BACKGROUND: We aimed to study whether positron emission tomography/computed tomography (PET/CT) findings are associated with lymph node staging, as outlined by the 7th edition American Joint Committee on Cancer (AJCC) TNM staging system in patients with esophageal squamous cell carcinoma (ESCC). METHODS: A series of 76 ESCC patients undergoing esophagectomy were included in this study. The relation between PET/CT findings [maximum standardized uptake value (SUVmax)] and pathologic lymph node status (N stage) was studied. RESULTS: The SUVmax of extra-tumor uptake, but not that of the main tumor, was significantly associated with the N classification. N2/N3 disease was observed in 61.1% of patients with an SUVmax for extra-tumor uptake of >4.9, whereas only 17.2% of patients with an SUVmax of extra-tumor uptake of <4.9 were classified as N2/N3 The number of PET abnormalities (NPAs) was also significantly associated with the N classification. Patients with three or more NPAs had a 65% chance of being classified as N2/N3, whereas patients with one or two NPAs had less than a 20% chance of being classified as N2/N3. CONCLUSIONS: The SUVmax of extra-tumor uptake and the NPAs were significantly associated with the N classification outlined by the 7th edition of the AJCC TNM staging system. PET/CT does help identify patients with advanced lymph node metastasis (N2/N3 stage) instead of simply indicating nodal involvement.

Design-around biotechnology patents: an analysis of US Federal Circuit decisions shows the possibility of designing around biotechnology patents.

In order to demonstrate the possibility of design-around for patents, we reviewed 40 no-infringement cases out of all 4,760 Federal Circuit Court of Appeals (CAFC) cases decided from 2001 to 2009. Based on this analysis, designing around a biotechnology patent first requires a thorough reading of the patent specification and prosecution history. These written descriptions offer explicit directions about claim meanings or the scope being disclaimed. By statute, claims recite and define the structure or acts of an invention, and serve as tools to determine whether or not a patent is infringed. The next procedure would include omitting a part or property from the claim, reversing the action used in the claim, or changing the claim's structure or range to prevent the new design from falling within the scope of the claim. However, cases where patent infringement was found demonstrated that changing the structure or range not recited in the claim, such as enlarging the diameter, reducing concentration or alerting the shape, still falls within the scope of the patent. Although the 40 cases analyzed in this study were not related to vaccines, the thought process can serve as a guideline for patents related to vaccine development.

The written description rejection as a barrier to biotech patent prosecution.

Biotech firms always pursue broad claims to secure new discoveries, new technologies and even as yet undiscovered results of future research. However, expansive claims without sufficient description violate the principal of granting the patentee the right to exclude others from using the technical development for a certain amount of time in return for disclosing the innovation. Based on this investigation, a written description can be a barrier to biotech patents with broad claims. To avoid a written description rejection during patent prosecution or invalidation in litigation, the patent applicant or assignee should demonstrate possession of the claimed invention by describing the claimed invention with all of its limitations using descriptive means such as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Although the court cases analyzed in this study were not directly related to vaccines, the guideline indeed is applicable to patents of vaccine. Furthermore, a vaccine patent application is also demonstrated.

The obviousness rejection as a barrier to vaccine patent prosecution.

After the US Supreme court's KSR case, the trends for obvious and non-obvious rulings in terms of the CAFC decisions significantly increased and decreased, respectively. In re Kubin case, the invention disclosed the isolation and sequences of a polynucleotide that encodes a Natural Killer Cell Activation Inducing Ligand (NAIL) polypeptide. The soluble NAIL polypeptides could serve as an adjuvant in combination with vaccines. However, the appellants employed conventional methods to isolate a cDNA encoding NAIL and determine the cDNA's full nucleotide sequence. Thus, the CAFC affirmed that a skilled artisan has a reasonable expectation of success in deriving the claimed invention in light of the teachings of the prior art. Based on this investigation, developers of human vaccines should contemplate the obvious barrier to patent prosecution. Furthermore, we also need to follow up the CAFC's decision on the patentability of the isolated DNA containing sequence. A CAFC dissenting opinion stressed that the difference between an isolated DNA sequence and the product occurring in nature is just in the isolated form. Such a patent would not be "markedly different characteristics from any found in nature."

The stem cell patent landscape as relevant to cancer vaccines.

Cancer vaccine targeting cancer stem cells is proposed to serve as a potent immunotherapy. Thus, it would be useful to examine the main trends in stem cell patenting activity as a guide for those seeking to develop such cancer vaccines. We found that a substantial number of stem cell patents were granted up to the end of 2010, including ~2000 issued in the US. Many of these have been filed since 2001, including 7,551 applications in the US. Stem cell development, as evidenced by the numbers of PubMed articles, has matured steadily in recent years. However, the other metrics, such as the number of patent applications, the technology-science linkage and the number of patent assignees, have been stagnant. Moreover, the ownership of stem cell patents is still quiet fragmented across multiple organizations, and the number of stem cell patent assignees from the business sector has not increased significantly. Academic and nonprofit institutions not only account for a large share of stem cell patents but also apply for patents continually. Based on this analysis, the strength of stem cell resources seems to remain stagnant in recent years due to the ban on government funding of embryonic stem cell research. Furthermore, the patent prosecution or technical barriers in the field of stem cells would be another main reason that the number of US-issued stem cell patents for each application have been in gradual decline since 2000. Therefore, we consider stem cell technology to still be under development.

Candida vaccines development from point view of US patent application.

Candidiasis is the fourth most common bloodstream infection in hospitalized patients in the United States. Moreover, the mortality rate from Candida infections remains high, even after treatment with antifungal therapy. Vaccination would be a promising strategy for prevention of invasive fungal infections. In order to examine the main trends in anticandidal vaccine patenting activity, we conducted an analysis for anticandidal vaccine patents. We find 190 issued patent and 940 patent application documents containing the keywords Candida and vaccine within claims in the USA. Candida vaccines development, as evidenced by the numbers of issued patents, has decreased since the year 2002. Furthermore, the number of patent applications in Candida vaccines may indicate the strength of engaged resources were also in the status of stagnation during 2005-2007 and even a decline in 2008. Academic and nonprofit research institutions not only account for a large share of Candida vaccines patents but also apply for patents continually. Based on this analysis, the strength of Candida vaccines resources seems to remain stagnant in recent years due to patent prosecution or technical barrier in the filed of Candida vaccines. Therefore, we consider that Candida vaccines technology to still be under development and the researchers are still looking for scientific breakthrough in the filed.

Printing a static progressive orthosis for hand rehabilitation.

BACKGROUND: Static progressive orthosis is used for the treatment of severe joint contracture after trauma and/or surgery. However, a custom-fabricated static progressive splint would be expensive and labor intensive. Especially, owing to very limited payment under the current Taiwanese National Health Insurance, the incentives to fabricate a patient-specific splint are insufficient for a therapist. To ease splint construction, we introduced three-dimensional (3D)-printed "shark fin"-shaped device works as a static progressive orthosis for the hand rehabilitation. The aim of this study was to describe and demonstrate the newly designed device. METHODS: This study included a 46-year male suffered from a left distal radius fracture and underwent open reduction internal fixation and a 23-year male with the right thumb flexor pollicis longus rupture, requiring tendon repair. Both subjects used this "shark fin"-shaped device to stretch for increasing range of motion (ROM) of wrist extension and the thumb. RESULTS: The patient receiving ulnar shortening surgery used this device to stretch for increasing ROM of wrist extension. The active ROM of wrist extension improved from 30° to 50°. The other patient with the right thumb flexor pollicis longus rupture suffered from thumb contracture; the ROMs of the metacarpophalangeal (MCP) joint and interphalangeal (IP) joint were 40°-55° and 20°-25°, respectively. After tenolysis surgery, his ROMs of the MCP and IP joints were improved to 10°-35° and 40°-65°, respectively. Following physical therapy by applying the device, his ROMs of the MCP and IP joints were further increased to 0°-40° and 25°-70°, respectively. CONCLUSION: Incorporating the "shark fin"-shaped orthosis into hand rehabilitation increased the ROM of wrist extension for a patient with distal radius fracture and improved the ROM of the MCP and IP joints in another patient after tenolysis surgery.