It's Time to Go Quantum in Medicine.

As the field of medicine grows and expands, new scientific developments hold great promise for improving quality of care, clinical research, and the diagnosis and treatment of diseases. Quantum physics is a promising field that intersects with medicine much more than originally understood. In terms of diagnosing different diseases, incorporating quantum mechanics into the study of medicine can allow for efficient diagnosis before symptoms even arise in a patient. Applying theory-based mathematical structures that describe neuron transmission throughout the brain and mind on a quantum scale can help us to better understand neurological diseases in patients. Quantum theory can even give plausible explanations for subtle DNA changes and even telomere reduction in patients who develop cancer. Utilizing quantum theory in the field of medicine can help in understanding and applying treatments for a multitude of different diseases, such as Alzheimer's disease or diverse types of cancer, and even expand upon efficient and reliable diagnosis in clinical settings. Quantum physics is a pertinent advancing field that may have a significant impact on expanding medical care and treatment in the near future. In this review, the application of quantum physics in medicine is discussed.

Novel Positioning Feedback System as a Guidance in Bone Tumor Resection.

Need: Bone resection using customized 3D-printed guides can improve accuracy, but the technique is still associated with clinically significant errors.Technical solution: We developed an inexpensive optical feedback system (OFS) that compares intraoperative 2D camera images to the pre-operative plan, and accurately depicts the surgeon's guide placement prior to cutting, reducing the errors in resection.Proof of concept: We simulated wide resections of a bone sarcoma on 24 cadaver femurs using 3 cutting guide types. Guide placement was measured using the OFS and compared to CT-scans showing the actual guide position. We carried out a second, controlled study on 20 sawbones, comparing the accuracy of the final bone cuts with and without the surgeon actively using the OFS to adjust the guide position before cutting.Results: For cadavers, in 2 of 3 planes, the position of the jig recorded by the OFS closely matched its actual position, with an accuracy of .87° ± .65°(r = .94) and 1.2° ± 1.3°(r = .81) in the transverse and sagittal planes, respectively. In the second study, OFS increased accuracy of the final cut about the transverse and sagittal planes, respectively by 53.1% (P = .011)/54.7% (P = .04) and 33% (P = .051)/38% (P = .042) in terms of rotation and translation.Next steps: Developing the OFS as a mobile application to reduce the processing time and improve accessibility in the operating room.Conclusion: The OFS could accurately depict the guide placement on the bone and significantly improve the surgical accuracy of 3D printed jigs.

3D-Printed Guides in Bone Tumor Resection: Studying Their Error and Determining a Safety Margin for Surgery.

3D-printed guides, which have recently been introduced in orthopedic oncology, improve resection accuracy compared with traditional bone resection methods, but there are inaccuracies associated with them. These inaccuracies could lead to disastrous outcomes such as positive tumor resection margins. In this Sawbone study, we sought to quantitatively investigate the margin of error for various jig types and to determine a "safety margin" that could serve as a guide for surgeons and jig engineers in creating 3D-printed jigs that would reduce the risk of potential disastrous results such as positive margins. Various 3D-printed jigs were used to simulate wide resection of a distal femoral bone sarcoma on Sawbone specimens by 10 individuals with no specific prior expertise in cutting guides. We developed a mathematical model using kinematic theory. We defined a safety margin as the amount of change in the osteotomy lines that must be incorporated into the jig design to ensure that the surgeon is at least 98% likely not to have a positive tumor margin. Experiments were conducted to determine the mean deviation experienced in placing cutting guides on the bones. The mean deviation for the four types of cutting guides ranged from 2.86 mm to 6.54 mm. We determined that a jig design should have a safety margin of 4.8 mm for standard guides and 8.65 mm for gusset guides to minimize the possibility of cutting into the tumor as a result of human error in guide placement. Further studies involving cadavers and patients are warranted. [Orthopedics. 2022;45(3):169-173.].

Biocompatible Customized 3D Bone Scaffolds Treated with CRFP, an Osteogenic Peptide.

BACKGROUND: Currently used synthetic bone graft substitutes (BGS) are either too weak to bear the principal load or if metallic, they can support loading, but can lead to stress shielding and are unable to integrate fully. In this study, we developed biocompatible, 3D printed scaffolds derived from µCT images of the bone that can overcome these issues and support the growth of osteoblasts. METHODS: Cylindrical scaffolds were fabricated with acrylonitrile butadiene styrene (ABS) and Stratasys® MED 610 (MED610) materials. The 3D-printed scaffolds were seeded with Mus musculus calvaria cells (MC3T3). After the cells attained confluence, osteogenesis was induced with and without the addition of calcitonin receptor fragment peptide (CRFP) and the bone matrix production was analyzed. Mechanical compression testing was carried out to measure compressive strength, stiffness, and elastic modulus. RESULTS: For the ABS scaffolds, there was a 9.8% increase in compressive strength (p < 0.05) in the scaffolds with no pre-coating and the treatment with CRFP, compared to non-treated scaffolds. Similarly, MED610 scaffolds treated with CRFP showed an 11.9% (polylysine pre-coating) and a 20% (no pre-coating) increase (p < 0.01) in compressive strength compared to non-treated scaffolds. CONCLUSIONS: MED610 scaffolds are excellent BGS as they support osteoblast growth and show enhanced bone growth with enhanced compressive strength when augmented with CRFP.

Clinical Validation of Rapid Gout Detection Method and Kit.

Gout is an inflammatory arthritis, which causes intense, acute pain due to the buildup of uric acid crystals in synovial fluid. The gold standard for gout diagnosis consists of synovial fluid analysis by polarized light microscopy, which is costly, time-intensive, and technique-dependent, therefore meriting a more efficient, inexpensive, and accessible method for diagnosis. We previously developed and validated a novel colorimetric gout detection method and device based on the reduction of silver nitrate by uric acid; here, we clinically validated our method and device using arthroscopically obtained synovial fluid samples from gout patients. We successfully identified uric acid crystals in clinical samples via our colorimetric method, visualized uric acid crystals in synovial fluid via handheld microscopy, and determined that silver nitrate stain did not interfere with the microscopic visualization of uric acid crystals necessary for diagnosis. We also developed and validated a method of processing turbid clinical samples for use in our device to prevent the obscuration of uric acid crystals by suspended material. Our method and device will clinically facilitate the immediate colorimetric diagnosis of gout and the subsequent bedside visualization of uric acid crystals in both ideal and turbid synovial fluid samples, allowing for a point-of-care diagnosis of gout.

Brugada syndrome.

Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome that causes a heightened risk for ventricular tachyarrhythmias and sudden cardiac death. BrS is characterised by a coved ST-segment elevation in right precordial leads. The prevalence is estimated to range between 1 in 5,000 to 1 in 2,000 in different populations, with the highest being in Southeast Asia and in males. More than 18 genes associated with BrS have been discovered and recent evidence has suggested a complex polygenic mode of inheritance with multiple common and rare genetic variants acting in concert to produce the BrS phenotype. Diagnosis of BrS in patients currently relies on presentation with a type-1 Brugada pattern on ECG either spontaneously or following a drug provocation test using a sodium channel blocker. Risk assessment in patients diagnosed with BrS is controversial, especially with regard to the predictive value of programmed electrical stimulation and novel ECG parameters, such as QRS fragmentation. The first line of BrS therapy remains an implantable cardioverter defibrillator (ICD), although radiofrequency catheter ablation has been shown to be an effective option in patients with contraindications for an ICD. True BrS can be unmasked on ECG in susceptible individuals by monitoring factors such as fever, and this has been recently evident in several patients infected with the 2019 novel coronavirus (COVID-19). Aggressive antipyretic therapy and regular ECG monitoring until fever resolves are current recommendations to help reduce the arrhythmic risk in these COVID-19 patients. In this review, we summarise the current knowledge on the epidemiology, pathophysiology, genetics, clinical diagnosis, risk stratification and treatment of patients with BrS, with special emphasis on COVID-19 comorbidity.

Rapid Gout Detection Method and Kit.

Gout is a form of arthritis characterized by buildup of uric acid in synovial fluid, which causes severe swelling and can harm joints, tendons, and other tissues. It affects approximately 4% of the United States population, or approximately 8.3 million people nationwide and is therefore a topic of epidemiologic consideration due to its prevalence. Gout is typically diagnosed via polarized microscopy of arthroscopically-aspirated synovial fluid, which is a costly, time-consuming, labor-intensive, and technically complex procedure, warranting a simpler and less complex method for diagnosis. Here, we propose and validate a colorimetric method which is based on the ability of uric acid to reduce silver nitrate. We also assessed how the colorimetric change can be accelerated by changing the concentration of silver nitrate or adding different silver catalysts, as well as develop a matrix bed for improved handling and ease of use. When translated to the clinic, this diagnostic method for gout will have the potential to increase diagnostic efficiency and accelerate patient care at the bedside.

Correction to: Biomechanical properties of 3D-printed bone scaffolds are improved by treatment with CRFP.

CORRECTION TO: J ORTHOP SURG RES (2017) 12: 195. HTTPS://DOI.ORG/10.1186/S13018-017-0700-2: In the original publication of this article [1] there was an error in one of the author names. In this publication the correct and incorrect name are indicated.

Biomechanical properties of 3D-printed bone scaffolds are improved by treatment with CRFP.

BACKGROUND: One of the major challenges in orthopedics is to develop implants that overcome current postoperative problems such as osteointegration, proper load bearing, and stress shielding. Current implant techniques such as allografts or endoprostheses never reach full bone integration, and the risk of fracture due to stress shielding is a major concern. To overcome this, a novel technique of reverse engineering to create artificial scaffolds was designed and tested. The purpose of the study is to create a new generation of implants that are both biocompatible and biomimetic. METHODS: 3D-printed scaffolds based on physiological trabecular bone patterning were printed. MC3T3 cells were cultured on these scaffolds in osteogenic media, with and without the addition of Calcitonin Receptor Fragment Peptide (CRFP) in order to assess bone formation on the surfaces of the scaffolds. Integrity of these cell-seeded bone-coated scaffolds was tested for their mechanical strength. RESULTS: The results show that cellular proliferation and bone matrix formation are both supported by our 3D-printed scaffolds. The mechanical strength of the scaffolds was enhanced by trabecular patterning in the order of 20% for compression strength and 60% for compressive modulus. Furthermore, cell-seeded trabecular scaffolds modulus increased fourfold when treated with CRFP. CONCLUSION: Upon mineralization, the cell-seeded trabecular implants treated with osteo-inductive agents and pretreated with CRFP showed a significant increase in the compressive modulus. This work will lead to creating 3D structures that can be used in the replacement of not only bone segments, but entire bones.

Cytokines as Biomarkers and Their Respective Clinical Cutoff Levels.

Cytokines, including interleukins, interferons, tumor necrosis factors, and chemokines, have a variety of pro- and anti-inflammatory effects in the body through a number of biochemical pathways and interactions. Stimuli, actions, interactions, and downstream effects of cytokines have been investigated in more depth in recent years, and clinical research has also been conducted to implicate cytokines in causal patterns in certain diseases. However, particular cutoffs of cytokines as biomarkers for disease processes have not been well studied, and this warrants future work to potentially improve diagnoses for diseases with inflammatory markers. A limited number of studies in this area are reviewed, considering diseases correlated with abnormal cytokine profiles, as well as specific cutoffs at which cytokines have been deemed clinically useful for diagnosing those diseases through Receiver Operator Characteristics modeling. In light of studies such as those discussed in this review, cytokine testing has the potential to support diagnosis due to its lack of invasiveness and low cost, compared to other common types of testing for infections and inflammatory diseases.

Ketamine enantiomers in the rapid and sustained antidepressant effects.

Recent evidence has suggested that the N-methyl-D-aspartate receptor antagonist ketamine shows significant therapeutic effects in major depression and bipolar disorder. This effect is especially important in treatment-resistant depression and depression with suicidal ideation. In this review we explain the mechanism of action, drug efficacy, and the side effects of ketamine; the antidepressive effects of ketamine; the individual effects of ketamine isomers, R(-) ketamine and S(+) ketamine; the effects of the combination of ketamine with electroconvulsive therapy; and the possible use of ketamine in treating depression.

Prostate cancer markers: An update.

As the most common noncutaneous malignancy in American men, prostate cancer currently accounts for 29% of all diagnosed cancers, and ranks second as the cause of cancer fatality in American men. Prostatic cancer is rarely symptomatic early in its course and therefore disease presentation often implies local extension or even metastatic disease. Thus, it is extremely critical to detect and diagnose prostate cancer in its earliest stages, often prior to the presentation of symptoms. Three of the most common techniques used to detect prostate cancer are the digital rectal exam, the transrectal ultrasound, and the use of biomarkers. This review presents an update regarding the field of prostate cancer biomarkers and comments on future biomarkers. Although there is not a lack of research in the field of prostate cancer biomarkers, the discovery of a novel biomarker that may have the advantage of being more specific and effective warrants future scientific inquiry.

Identification and Characterization of a Synthetic Osteogenic Peptide.

Osteoporosis is the most common metabolic bone disorder and its management represents a tremendous public health encumbrance. While several classes of therapeutics have been approved to treat this disease, all are associated with significant adverse effects. An algorithm was developed and utilized to discover potential bioactive peptides, which led to the identification of an osteogenic peptide that mapped to the C-terminal region of the calcitonin receptor and has been named calcitonin receptor fragment peptide (CRFP). In vitro treatment of human mesenchymal stem cells with CRFP resulted in dose-specific effects on both proliferation and osteoblastic differentiation. Similarly, in vitro treatment of rat RCJ3.1C5.18 cells led to dose- and species-specific effects on proliferation. A rat ovariectomy (OVX) model was used to assess the potential efficacy of CRFP in treating osteoporosis. MicroCT analysis of distal femoral samples showed that OVX rats treated with CRFP were significantly protected from losses of 55 % in trabecular bone volume fraction (BVF), 42 % in connectivity density, and 18 % in trabecular thickness in comparison to vehicle-treated controls. MicroCT analyses of vertebrae revealed CRFP to significantly prevent a 25 % reduction in BVF. MicroCT evaluation of femoral and vertebral cortical bone found a significant reduction of 2 % in vertebral bone mineral density. In summary, our in vitro studies indicate that CRFP is both bioactive and osteogenic and our in vivo studies indicate that CRFP is skeletally bioactive. These promising data indicate that further in vitro and in vivo evaluation of CRFP as a new treatment for osteoporosis is warranted.

A Novel Point-of-Care Biomarker Recognition Method: Validation by Detecting Marker for Diabetic Nephropathy.

Biological fluid collection to identify and analyze different disease markers is a routine and normal procedure in health care settings. Body fluids are as varied as urine, blood, mucus, cerebrospinal fluid (CSF), tears, semen, etc. The volumes of the collected fluids range from micro liters (e.g., tears, CSF) to tens and hundreds of milliliters (blood, urine, etc.). In some manifestations, a disease marker (particularly protein markers) can occur in trace amounts, yet the fluids collected are in large volumes. To identify these trace markers, cumbersome methods, expensive instruments, and trained personnel are required. We developed an easy method to rapidly capture, concentrate, and identify protein markers in large volumes of test fluids. This method involves the utilization of two antibodies recognizing two different epitopes of the protein biomarker. Antibody-1 helps to capture and concentrate the biomarker and Antibody-2 adsorbed or conjugated to nanogold beads will detect the biomarker. This method was validated in capturing and detecting lipocalin type prostaglandin-D2 synthase, a marker in urine that implicates diabetic nephropathy. A one-step collection, concentration, and detection device was designed based on this method. This device can replace many of the normal body fluid collection devices such as tubes and containers. A one-step fluid collection and biomarker capture and concentration device for rapid diagnosis of diseases has tremendous advantage in terms of cost and providing timely results.

Temporomandibular joint disorder and inner ear pruritus: resolution by eminectomy.

Recurrent dislocation of the temporomandibular joint (TMJ) disk is caused by many factors. Dislocation can result in an acute or chronic closed lock condition. Temporomandibular joint dysfunction is often presented with otalgia symptoms. Other aural symptoms such as deafness, tinnitus, pressure/blockage, and vertigo are also commonly presented together with TMJ dysfunction (Clin Otolaryngol Allied Sci. 1980;5:23-36). However, pruritus associated with TMJ dysfunction in the inner ear has never been reported in the literature. We report a case history of TMJ dysfunction and associated inner ear pruritus, which are both resolved by eminectomy.

Evaluation of prostaglandin D2 as a CSF leak marker: implications in safe epidural anesthesia.

BACKGROUND: It is accepted that there is a severe risk of dural puncture in epidural anesthesia. Of major concern to anesthesiologists is unintentional spinal block. Reliable identification of cerebrospinal fluid (CSF) from the aspirate is crucial for safe epidural anesthesia. The aim of this study was to determine whether prostaglandin D2 could be clinically used as a marker for the detection of CSF traces. METHODS: After obtaining Institutional Review Board approval and patient consent, CSF was obtained from patients undergoing spinal anesthesia, and blood, urine, and saliva were obtained from normal subjects and analyzed for prostaglandin D2 (PGD). CSF (n=5) samples were diluted with local anesthetic (bupivacaine), normal saline and blood in the ratios of 1:5 and 1:10. PGD levels in the CSF samples were analyzed with a PGD-Methoxime (MOX) EIA Kit (Cayman Chemicals, MI). This assay is based on the conversion of PGD to a stable derivative, which is analyzed with antiserum specific for PGD-MOX. RESULTS: Different concentrations of pure PGD-MOX conjugate were analyzed by EIA and a standard curve was derived. PGD levels in CSF and CSF with diluents were determined and the values were extrapolated onto the standard curve. Our results show a well-defined correlation for the presence of PGD both in straight CSF samples and in diluted CSF (dilution factor of 1:5 and 1:10). CONCLUSION: Prostaglandin D2 was reliably identified in CSF by enzyme-linked immunosorbent assay when diluted with local anesthetic, saline, and serum, and can be used as a marker to identify the presence of CSF in epidural aspirates.

Effect of n-Alkanols on G-Protein α Subunits.

Guanine nucleotide binding (G)-proteins are GTP-driven allosteric proteins consisting of a single α subunit and a ß and γ heterodimer. Gα subunits function as on/off switches based on the occupancy of the nucleotide-binding site, GTP or GDP, such that any alteration in nucleotide exchange modulates signal output. Our previous work has shown that haloalkanes and ethers inhibit GDP/GTP exchange on αi1, αi2 and αi3 subunits, but not the closely related αo. To test whether individual G-protein sensitivity correlates with n-alkanols potency and hydrophobicity, we studied the effects of n-alkanols of varied chain lengths on GDP/GTP exchange by Gαsubunits. n-alkanols (ethanol, butanol, pentanol, hexanol, heptanol, octanol and nonanol) showed differential effects on guanine nucleotide exchange by Gαi1, Gαi2 and Gαo. Based on our observations, we conclude that n-alkanols interact and modulate the activity of the G-α subunits to different extent, thereby uncoupling pathways known to modulate neuronal excitation.

Microsomal Ca2+ flux modulation as an indicator of heavy metal toxicity.

Inositol 1,4,5-trisphosphatee (IP3), an intracellular messenger, releases Ca2+ from microsomes. Ca2+ plays a major role in regulating various cellular events like neural transmission and regulation of hormones and growth factors. Aluminum (Al), lead (Pb) and mercury (Hg) were reported to alter Ca(2+)-regulated events thereby causing neurotoxicity. Hence, an attempt was made characterize IP3 mediated Ca2+ release from rat brain microsomes under the influence of Al, Pb and Hg. Different concentrations of metals were tested over a designated time scale and their effects on IP3 mediated Ca2+ release from microsomes were monitored using Fura-2 technique. All the three metals inhibited IP3 mediated Ca2+ release, Pb being more potent. The order of potency of these three metals was Pb>Hg>Al. Except for Al, both Hg and Pb independently released Ca2+ from microsomes. Re-uptake of Ca2+ into microsomes was inhibited by all the three metals, Pb being more potent. Microsomal Ca(2+)-ATPase activity was also inhibited by all the three metals. These results suggest that neurotoxicity exerted by Al, Pb and Hg may be due to the interference of these metals with IP3 mediated calcium release and also interfering with the microsomal Ca2+ sequestration mechanism. Differential effects of heavy metal induced changes in Ca2+ flux can be used as an index of relative toxicity.

Current perspectives on pyospermia: a review.

Pyospermia is an abnormal laboratory finding of high concentration of white blood cells in human ejaculates during infertility workup. The role of pyospermia and its impact on fertility is an important consideration in the management of infertility. Etiology, pathogenesis, diagnostic modalities and the management of pyospermia are reviewed in this paper. Current use of antibiotics and the intrinsic production of antioxidants in the management of pyospermia are also discussed in this review.

Nuclear translocation of phospholipase C-delta1 is linked to the cell cycle and nuclear phosphatidylinositol 4,5-bisphosphate.

Nuclear phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate, fluctuate throughout the cell cycle and are linked to proliferation and differentiation. Here we report that phospholipase C-delta(1) accumulates in the nucleus at the G(1)/S boundary and in G(0) phases of the cell cycle. Furthermore, as wild-type protein accumulated in the nucleus, nuclear phosphatidylinositol 4,5-bisphosphate levels were elevated 3-5-fold, whereas total levels were decreased compared with asynchronous cultures. To test whether phosphatidylinositol 4,5-bisphosphate binding is important during this process, we introduced a R40D point mutation within the pleckstrin homology domain of phospholipase C-delta(1), which disables high affinity phosphatidylinositol 4,5-bisphosphate binding, and found that nuclear translocation was significantly reduced at G(1)/S and in G(0). These results demonstrate a cell cycle-dependent compartmentalization of phospholipase C-delta(1) and support the idea that relative levels of phosphoinositides modulate the portioning of phosphoinositide-binding proteins between the nucleus and other compartments.