A comparison increasing the photodegradation power of a Ag/g-C3N4 /CoNi-LDH nanocomposite: Photocatalytic activity toward water treatment.

For environmental applications, it is crucial to rationally design and synthesize photocatalysts with positive exciton splitting and interfacial charge transfer. Here, a novel Ag-bridged dual Z-scheme Ag/g-C3N4/CoNi-LDH plasmonic heterojunction was successfully synthesized using a simple method, with the goal of overcoming the common drawbacks of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers, and unstable structure. These materials were characterized by XRD, FT-IR, SEM, TEM UV-Vis/DRS, and XPS to verify the structure and stability of the heterostructure. The pristine LDH, g-C3N4, and Ag/g-C3N4/CoNi-LDH composite were investigated as photocatalysts for water remediation, an environmentally motivated process. Specifically, the photocatalytic degradation of tetracycline was studied as a model reaction. The performance of the supports and composite catalyst were determined by evaluating both the degradation and adsorption phenomenon. The influence of several experimental parameters such as catalyst loading, pH, and tetracycline concentration were evaluated. The current study provides important data for water treatment and similar environmental protection applications.

Targeting cis-p-tau and neuro-related gene expression in traumatic brain injury: therapeutic insights from TC-DAPK6 treatment in mice.

BACKGROUND: Traumatic brain injury (TBI) is a significant global health concern and is characterized by brain dysfunction resulting from external physical forces, leading to brain pathology and neuropsychiatric disorders such as anxiety. This study investigates the effects of TC-DAPK6 on tau hyper-phosphorylation, gene expression, anxiety, and behavior impairment in the TBI mice model. METHODS AND RESULTS: A weight drop model induced the TBI and the anxiety levels were evaluated using an elevated plus maze (EPM) test. TC-DAPK6 was intraperitoneally administered one-month post-TBI and continued for two months. The total cis-p-tau ratio in the brain was assessed using western blot and immunofluorescence staining. Molecular analysis was conducted on Aff2, Zkscan16, Kcna1, Pcdhac2, and Pcdhga8 to investigate the function and pathogenic role of TC-DAPK6 in neurological diseases in the cerebral cortex tissues of TBI-model mice, and the results were compared with TC-DAPK6 TBI-treatment group. The anxiety level and phosphorylation of tau protein in the TBI group were significantly increased compared to the sham groups and decreased substantially in the TBI-treatment group after TC-DAPK6 administration; the TBI group mostly spent their time with open arms. TC-DAPK6 decreased the expression level of genes as much as the sham group. Meanwhile, KCNA1 showed the highest fold of changes in the TBI and TBI-treatment groups. CONCLUSIONS: The study demonstrates a clear association between cis-p-tau and neuro-related gene expression levels in TBI-induced mice. Targeting these pathways with DAPK1 inhibitors, shows promise for therapeutic interventions in TBI and related neurodegenerative disorders.

Wafer-Scale MgB2 Superconducting Devices.

Progress in superconducting device and detector technologies over the past decade has realized practical applications in quantum computers, detectors for far-infrared telescopes, and optical communications. Superconducting thin-film materials, however, have remained largely unchanged, with aluminum still being the material of choice for superconducting qubits and niobium compounds for high-frequency/high kinetic inductance devices. Magnesium diboride (MgB2), known for its highest transition temperature (Tc = 39 K) among metallic superconductors, is a viable material for elevated temperature and higher frequency superconducting devices moving toward THz frequencies. However, difficulty in synthesizing wafer-scale thin films has prevented implementation of MgB2 devices into the application base of superconducting electronics. Here, we report ultrasmooth (<0.5 nm root-mean-square roughness) and uniform MgB2 thin (<100 nm) films over 100 mm in diameter and present prototype devices fabricated with these films demonstrating key superconducting properties including an internal quality factor over 104 at 4.5 K and high tunable kinetic inductance in the order of tens of pH/sq in a 40 nm thick film. This advancement will enable development of elevated temperature, high-frequency superconducting quantum circuits, and devices.

Pathological Variables and Laboratory Values in Infants with Neonatal Cholestasis Showing Nonexcretion on Tc-99m Mebrofenin Hepatobiliary Scans: A Descriptive Study.

Introduction: Cholescintigraphy using Tc-99m Mebrofenin is routinely performed as an initial diagnostic test in infants with neonatal cholestasis suspected of having biliary atresia. Demonstration of drainage of bile into the small intestine indicates patency of the biliary tract and thus rules out biliary atresia. Non-excretion of tracer into the small intestine, however, can be caused by obstructive as well as non-obstructive conditions, and it is known that false-positive findings are found with the use of Tc-99m Mebrofenin scintigraphy. Aim: In the present study, we retrospectively calculated the proportion of infants eventually diagnosed to have biliary atresia that were initially ruled to have a non-excreting cholescintigraphy pattern in our institution. We have also attempted a systematic description of the cardinal histological characteristics, haematological and hepatic biochemical variables in infants with non-excreting patterns. Materials and Methods: This retrospective, descriptive study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry. We reviewed data from infants who underwent cholescintigraphy with Tc-99m Mebrofenin between January 2016 through June 2022. We included infants in whom the scan was ruled "non-excreting" i.e. those infants in whom biliary atresia could not be ruled out based on the results of the scan. The difference in mean for haematological parameters and ALP were compared between the two groups i.e., biliary atresia versus other than biliary atresia by using Independent student's t-test; the remaining liver biochemical parameters were compared by using Mann-Whitney U Test and a p value < 0.05 was considered to be statistically significant. Results: A non-excretory pattern on cholescintigraphy was found to be due to biliary atresia in 49% of cases (as confirmed by exploratory surgery) and an additional 19.6 % of cases by trucut biopsy (total 68.6%). The difference in the mean serum GGT levels was found to be statistically significant (<0.001). Conclusion: A non-draining pattern on cholescintigraphy is caused by biliary atresia in the greater percentage of cases presenting with cholestasis. The difference in mean GGT levels was found to be statistically significant between biliary atresia and other causes of non-draining patterns on cholescintigraphy.

The [99mTc]Tc-HMPAO-labelled white blood cell SPECT/CT as a novel criterion for infective endocarditis diagnosis.

AIMS: Infective endocarditis (IE) poses a significant clinical challenge, necessitating nuanced diagnostic tools for early and accurate detection. The diagnostic role of the hybrid technique of single-photon emission tomography-computed tomography with technetium-99 m-hexamethylpropyleneamine oxime-labelled leukocytes ([99mTc]Tc-HMPAO-SPECT/CT) has evolved in recent years. This single-center study assessed whether the recent inclusion in the 2023 European Society of Cardiology modified diagnostic criteria of IE (2023 ESC) of infectious lesions detected with [99mTc]Tc-HMPAO-SPECT/CT affects their diagnostic performance. METHODS AND RESULTS: Between 2015 and 2019, we enrolled 205 consecutive adults with suspected IE. All participants underwent [99mTc]Tc-HMPAO-SPECT/CT scans (370-740 MBq). Scans were deemed positive in the presence of intracardiac abnormal tracer uptake and/or within the cardiac implantable electronic device. Patients were prospectively followed-up for 12 ± 10 months. Local device infection (LDI) or IE was diagnosed in 75 (36.6 %) patients, while 72 (35.1 %) [99mTc]Tc-HMPAO-SPECT/CT results returned positive. Moreover, extracardiac infectious foci were detected in 25 % of [99mTc]Tc-HMPAO-SPECT/CT scans. The inclusion of both intracardiac and extracardiac lesions detected with [99mTc]Tc-HMPAO-SPECT/CT yields significantly higher sensitivity (p = 0.003) and negative predictive value (NPV) (p = 0.009). CONCLUSION: The inclusion of [99mTc]Tc-HMPAO-SPECT/CT into the IE diagnostic work-up improves the appropriate classification of patients. For patients with IE, the extended inclusion of lesions detected with [99mTc]Tc-HMPAO-SPECT/CT in the ESC 2023 diagnostic criteria significantly improves sensitivity and NPV while reducing potential IE misdiagnoses. This pioneering imaging modality is poised to become an integral component of clinical practice, promising to advance IE diagnosis and management.

Contrast-enhanced ultrasound image sequences based on radiomics analysis for diagnosis of metastatic cervical lymph nodes from thyroid cancer.

Background: Thyroid cancer (TC) prone to cervical lymph node (CLN) metastasis both before and after surgery. Ultrasonography (US) is the first-line imaging method for evaluating the thyroid gland and CLNs. However, this assessment relies mainly on the subjective judgment of the sonographer and is very much dependent on the sonographer's experience. This prospective study was designed to construct a machine learning model based on contrast-enhanced ultrasound (CEUS) videos of CLNs to predict the risk of CLN metastasis in patients with TC. Methods: Patients who were proposed for surgical treatment due to TC from August 2019 to May 2020 were prospectively included. All patients underwent US of CLNs suspected of metastasis, and a 2-minute imaging video was recorded. After target tracking, feature extraction, and feature selection through the lymph node imaging video, three machine learning models, namely, support vector machine, linear discriminant analysis (LDA), and decision tree (DT), were constructed, and the sensitivity, specificity, and accuracy of each model for diagnosing lymph nodes were calculated by leave-one-out cross-validation (LOOCV). Results: A total of 75 lymph nodes were included in the study, with 42 benign cases and 33 malignant cases. Among the machine learning models constructed, the support vector machine had the best diagnostic efficacy, with a sensitivity of 93.0%, a specificity of 93.8%, and an accuracy of 93.3%. Conclusions: The machine learning model based on US video is helpful for the diagnosis of whether metastasis occurs in the CLNs of TC patients.

Prospective Study Comparing [99mTc]Tc-DP-FAPI Quantitative SPECT/CT with [68Ga]Ga-FAPI-04 PET/CT in Patients with Gastrointestinal Tumors.

Over the past decade, [68Ga]Ga-FAPI-04 positron emission tomography (PET)/CT imaging has been widely used for the treatment of various tumors. However, the application of 99mTC-labeled fibroblast activation protein inhibitors in tumors has been less studied. Our team previously demonstrated the safe biological distribution of [99mTc]Tc-DP-FAPI in the human body. Based on this, this study reports the accuracy of [99mTc]Tc-DP-FAPI in the imaging diagnosis of gastrointestinal tumors and compares it with that of [68Ga]Ga-FAPI-04 to evaluate the differences. A total of 24 patients with clinically diagnosed gastrointestinal tumors were prospectively included. All patients received [99mTc]Tc-DP-FAPI quantitative SPECT/CT imaging on the first day and [68Ga]Ga-FAPI-04 PET/CT imaging on the second day. And the effectiveness of the two imaging probes in detecting suspicious lesions was analyzed and compared. The primary tumors of all 24 patients were well detected by two imaging probes, and the sensitivity of [99mTc]Tc-DP-FAPI and [68Ga]Ga-FAPI-04 to the primary lesions was 100%. [99mTc]Tc-DP-FAPI examined 21 lymph nodes with a sensitivity and specificity of 32.8% and 10.9%, and [68Ga]Ga-FAPI-04 detected 57 lymph nodes with a sensitivity and specificity of 89.1% and 67.2%, respectively. Three distant metastases were detected by [99mTc]Tc-DP-FAPI and nine metastases by [68Ga]Ga-FAPI-04. The study showed that [99mTc]Tc-DP-FAPI is highly sensitive to detecting primary lesions of gastrointestinal tumors. Compared with [68Ga]Ga-FAPI-04, [99mTc]Tc-DP-FAPI has the same sensitivity in detecting primary tumors but has certain limitations in detecting metastases. [99mTc]Tc-DP-FAPI is of great value for preliminary screening of tumor lesions and early diagnosis of disease in patients who are suspected of having gastrointestinal tumors.

Photo-assisted conversion of tetracycline in regulated persulfate system: Multiple roles of natural dissolved organic matter.

Advanced oxidation processes (AOPs) using persulfate system can effectively remove organic pollutants. However, dissolved organic matter (DOM) has multiple effects on AOPs efficiency, and the influence of DOMs from natural sources on AOPs is still unclear. In this study, we explored the effects of soil DOM (SDOM) and fertilizer DOM (FDOM) on tetracycline (TC) removal by persulfate systems. DOMs introduction decreased light transmittance, slightly increased the pH of the systems, and destroyed original adsorption-desorption equilibrium. SDOM promoted most reactive species generation in the initial stage, thus improving the initial TC degradation rate. However, introduction of SDOM and FDOM increased the final TC residual rate. FDOM produced more obvious inhibitory effects on TC degradation. The final TC residual rates in systems containing 7.5 and 15 mg L-1 FDOM (F7.5-TC-PS and F15-TC-PS, respectively) were 25.85 % and 25.52 %, respectively. The inhibitory effects of FDOM on TC degradation were related to the combination between TC and FDOM, with humic acid-like component in FDOM being the main contributor. Besides, the main components in DOMs underwent transformation in the persulfate systems. This study sought to provide insights into the regulatory effects of DOM on TC photo-assisted conversion by AOPs.

Ultra-fast, selective and pseudo-quantitative analysis of 99Tc in nuclear waste for screening purposes.

Controlling radioactivity is essential in various fields, such as the decommissioning of nuclear power plants and nuclear medicine. In some cases, a full characterization of samples is not required; instead, a screening analysis that provides an overall indication of the activity present can be sufficient to determine if a sample is radioactive. This article introduces a new system called PSkits designed specifically for ultra-fast and selective screening detection of 99Tc. PSkits consist of a plastic scintillation layer attached to the bottom of a scintillation vial, coated with aliquat·336® as a selective extractant. In this study, the preparation of PSkits was optimized by adjusting the proportions of crosslinker, porogen, and the type of vial used. The analysis method was developed, and the selectivity against common interferences was tested by optimizing the rinsing media. Finally, PSkits were validated by analysing simulated nuclear waste samples and urine spiked samples, achieving satisfactory results with quantification errors below 50 %, demonstrating their effectiveness for the intended purpose.

Trigeminal neuralgia, demyelinating polyneuropathy, and central nervous system involvement in a patient with an SH3TC2 mutation.

BACKGROUND: Charcot-Marie-Tooth type 4C (CMT4C) is a slowly progressive, autosomal recessive, sensorimotor polyneuropathy characterized by demyelination and distinct clinical features, including cranial nerve involvement. CMT4C is associated with pathogenic mutations in the SH3TC2 gene. METHODS: A patient presenting with gait instability due to demyelinating polyneuropathy and refractory trigeminal neuralgia underwent comprehensive evaluation. Nerve conduction studies, magnetic resonance imaging (MRI) of the brain, cervical spine, and thoracic spine, lumbar puncture, and genetic test through next generation sequencing were performed. RESULTS: The genetic test found an Arg1109Stop mutation in the SH3TC2 gene, associated with demyelinating polyneuropathy and cranial neuropathy. Interestingly, brain MRI showed multiple, nonenhancing white matter hyperintensities. This is the first case of CMT4C associated with white matter lesions. CONCLUSION: Any patient with slowly progressive peripheral nervous system symptoms and disproportionally abnormal nerve conduction study findings should be tested for an inherited polyneuropathy and brain imaging for screening of possible central nervous system involvement should be performed. Further investigation is needed to elucidate the pathogenetic basis of CMT4C and a possible association with white matter lesions.

Sensitive and selective detection of tetracycline using fluorescence-enhanced Eu(III)-functionalized silver nanoparticles with homocysteine.

Utilizing metal luminescence enhancement to design fluorescent probes is a very sensible strategy. Herein, a fluorescent probe based on europium (III)-functionalized silver nanoparticles-conjugated homocysteine (AgNPs-Hcy-Eu3+) was proposed for the selective and sensitive detection of tetracycline (TC). In this probe, Eu(III) was employed as the detection signal unit for TC, while AgNPs-Hcy was used as the ligand of fluorescence enhancement. When TC exists, it can bind to Eu3+ immobilized in AgNPs-Hcy, leading to an enhanced fluorescence signal from Eu3+ through energy transfer. Under optimal conditions, the fluorescence intensity of AgNPs-Hcy-Eu3+ increased linearly with increasing TC concentration in the range of 0.1-30 µM (R2 = 0.9964). The fluorescent probe own fluorescence enhancement, paving the way for sensitive detection with a low detection limit of 0.083 µM. It also has good selectivity for common antibiotics and anions. This work can be applied to the determination of TC in tap water and milk with recoveries of 94-98.5%. We expect AgNPs-Hcy-Eu3+ to have potential applications in environmental testing and food safety.

A europium (III) functionalized hydrogen-bonded organic framework for sensitively ratiometric fluorescent sensing of tetracycline.

As a kind of antibiotic, tetracycline (TC) might remain in animal blood and milk products during use, which poses a risk to humans after consumption. Therefore, a ratiometric fluorescence probe was proposed for the detection of TC, which was based on an Eu3+ functionalized hydrogen-bonded organic framework (HOF). Since there are a large number of N and O atoms in the skeleton of HOF, more Eu3+ could be loaded onto HOF by forming coordinate bonds, while preserving the fluorescence of luminol monomer in HOF. In the presence of TC, the fluorescence of luminol monomer was attenuated at 425 nm due to inner filter effect (IFE), while TC selectively enhanced the fluorescence peak at 617 nm of Eu3+ under the influence of antenna effect (AE). This highly sensitive probe could detect TC in the range of 0.1-60 µM and had a low limit of detection of 8.51 nM. Besides, the HOF@Eu probe was able to detect TC in actual samples (milk and tap water) with good recoveries (95.09%-111.51%) and precision (R < 4.78%), indicating this probe has great application potential for the detection of TC in food.

Real-world effectiveness and safety of switching to dolutegravir/lamivudine among people living with HIV-1 aged over 50 years who are virologically suppressed.

OBJECTIVES: People living with HIV face several challenges as they age, including the potential for polypharmacy and increased susceptibility to drug-related adverse effects. Thus, effective and well-tolerated regimens with minimal or no drug interactions would be useful in this population. We present real-world effectiveness and safety data for individuals aged >50 years who achieved virological suppression (HIV-1 RNA <50 copies/mL) and switched to dolutegravir/lamivudine (DTG/3TC). METHODS: This retrospective, observational, single-centre study conducted in Portugal included individuals aged >50 years who switched to DTG/3TC while virologically suppressed and had ≥12 months of follow-up. Proportions of individuals maintaining virological suppression were described at 12 months; CD4+ cell counts were described at baseline and 12 months. Descriptive subgroup analyses were performed based on age, sex assigned at birth, and availability of historical genotypic resistance results. RESULTS: Overall, 538 individuals aged >50 years were included (74% male; mean age, 62 years; mean time on previous therapy, 160 months). High proportions (intention-to-treat population, 97%; on-treatment population, 98%) of individuals who switched to DTG/3TC maintained virological suppression through 12 months of follow-up. CD4+ cell counts remained stable (mean baseline: 727 cells/mm3 [range 94-2371]; mean month 12: 742 cells/mm3 [range 99-2659]). No individuals experienced virological failure. Nine (2%) individuals discontinued DTG/3TC for non-treatment-related reasons. Proportions with virological suppression at month 12 were similar between on-treatment subgroups by age, sex assigned at birth, and historical genotypic resistance results availability. CONCLUSIONS: DTG/3TC demonstrated robust effectiveness and a good safety profile in individuals aged >50 years with virological suppression in Portugal.

[Acquired severe aplastic anemia in emerging countries: Management from allogeneic hematopoietic cell transplantation indication until post-transplant follow-up SFGM-TC]. / Aplasies médullaires sévères acquises dans les pays émergents : prise en charge dès l'indication de l'allogreffe de cellules souches hématopoïétiques jusqu'au suivi postgreffe (SFGM-TC).

Management of acquired aplastic anemia (AA) in emerging countries depends on the means of prognostic stratification, treatment and logistics available. During the 13th annual harmonization workshop of the francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC), a designated working group reviewed the literature in order to elaborate unified guidelines for allogeneic hematopoietic cell transplantation (Allo-HCT) in this disease. In terms of practice, the conclusions are as follows; The use of anti-tymocyte globuline (ATG) is mainly from rabbit and very little from horse. Access to bone marrow graft, total body irradiation, and the international unrelated donor registries is limited, which justifies the use of peripheral blood stem cells, chemotherapy-based conditioning, and related alternative donor. The workshop recommends matched sibling allo-HCT in all patients aged less than 40 years with acquired severe or very severe AA. For patients aged over than 40 years, or who lack an HLA-identical donor, treatment with the combination of cyclosporin, horse ATG, eltrombopag or cyclosporine, eltrombopag is recommended. If horse ATG and eltrombopag are not available, matched sibling allo-HCT may be indicated as first-line therapy in patients aged between 40-60 years, and good performance status. Although, in patients who have failed immunosuppressive treatments and thrombopoietin agonists, and in the absence of HLA-matched donor, a haplo-identical allo-HCT with modified Baltimore conditioning is recommended.

Influence of Laser Power and Rotational Speed on the Surface Characteristics of Rotational Line Spot Nanosecond Laser Ablation of TC4 Titanium Alloy.

The TC4 titanium alloy is widely used in medical, aerospace, automotive, shipbuilding, and other fields due to its excellent comprehensive properties. As an advanced processing technology, laser processing can be used to improve the surface quality of TC4 titanium alloy. In the present research, a new type of rotational laser processing method was adopted, by using a beam shaper to modulate the Gaussian spot into a line spot, with uniform energy distribution. The effects of the laser power and rotational speed on the laser ablation surface of the TC4 titanium alloy were analyzed. The results reveal that the melting mechanism of the material surface gradually changes from surface over melt to surface shallow melt with the increase in the measurement radius and the surface roughness increases first, then decreases and, finally, tends to be stable. By changing the laser power, the surface roughness changes significantly with the variation in the measurement radius. Because low laser power cannot provide sufficient laser energy, the measurement radius corresponding to the surface roughness peak of the microcrack area is reduced. Under a laser power of 11 W, the surface roughness reaches its peak when the measurement radius is 600 µm, which is 200 µm lower than that of a laser power of 12 W, 13 W, and 14 W. By changing the rotational speed, the centrifugal force generated by the rotation of the specimen affects the distribution and re-condensation of the molten pool of the surface. As the rotational speed increases, the shallow pit around the pit is made shallower by the filling of the pit with molten material and the height of the bulge decreases, until it disappears. The surface oxygen content of the material increases first and then decreases with the increase in the measurement radius and gradually approaches the initial surface state. Compared with a traditional laser processing spot, the rotational line spot covers a larger processing area of 22.05 mm2. This work can be used as the research basis for rotational modulation laser polishing and has significance for guiding the innovative development of high-quality and high-efficiency laser processing technology.

Study on Laser Transmission Welding Technology of TC4 Titanium Alloy and High-Borosilicate Glass.

As the demand for high-performance dissimilar material joining continues to increase in fields such as aerospace, biomedical engineering, and electronics, the welding technology of dissimilar materials has become a focus of research. However, due to the differences in material properties, particularly in the welding between metals and non-metals, numerous challenges arise. The formation and quality of the weld seam are strongly influenced by laser process parameters. In this study, successful welding of high-borosilicate glass to a TC4 titanium alloy, which was treated with high-temperature oxidation, was achieved using a millisecond pulsed laser. A series of process parameter comparison experiments were designed, and the laser welding behavior of the titanium alloy and glass under different process parameters was investigated using scanning electron microscopy (SEM) and a universal testing machine as the primary analysis and testing equipment. The results revealed that changes in process parameters significantly affect the energy input and accumulation during the welding process. The maximum joint strength of 60.67 N was obtained at a laser power of 180 W, a welding speed of 3 mm/s, a defocus distance of 0 mm, and a frequency of 10 Hz. Under the action of the laser, the two materials mixed and penetrated into the molten pool, thus achieving a connection. A phase, Ti5Si3, was detected at the fracture site, indicating that both mechanical bonding and chemical bonding reactions occurred between the high-borosilicate glass and the TC4 titanium alloy during the laser welding process.

An emerging role of STriatal-Enriched protein tyrosine Phosphatase in hyperexcitability-associated brain disorders.

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase that is associated with numerous neurological and neuropsychiatric disorders. STEP dephosphorylates and inactivates various kinases and phosphatases critical for neuronal function and health including Fyn, Pyk2, ERK1/2, p38, and PTPα. Importantly, STEP dephosphorylates NMDA and AMPA receptors, two major glutamate receptors that mediate fast excitatory synaptic transmission. This STEP-mediated dephosphorylation leads to their internalization and inhibits both Hebbian synaptic potentiation and homeostatic synaptic scaling. Hence, STEP has been widely accepted to weaken excitatory synaptic strength. However, emerging evidence implicates a novel role of STEP in neuronal hyperexcitability and seizure disorders. Genetic deletion and pharmacological blockade of STEP reduces seizure susceptibility in acute seizure mouse models and audiogenic seizures in a mouse model of Fragile X syndrome. Pharmacologic inhibition of STEP also decreases hippocampal activity and neuronal intrinsic excitability. Here, we will highlight the divergent roles of STEP in excitatory synaptic transmission and neuronal intrinsic excitability, present the potential underlying mechanisms, and discuss their impact on STEP-associated neurologic and neuropsychiatric disorders.

Comparison of intraoperative imaging with a portable gamma camera with extemporaneous histology in minimally invasive surgery for primary hyperparathyroidism.

INTRODUCTION: The curative treatment of primary hyperparathyroidism (PPH) is surgical and today it can be performed by minimally invasive surgery (MIS) and also be radioguided (RG) if a radiopharmaceutical with affinity for the parathyroid tissue that can be detected with gamma-detector probes or with a portable gamma camera (PGC) is injected. AIM: The objective is to assess whether intraoperative scintigraphy (GGio) with PGC can replace intraoperative pathological anatomy (APio) to determine if the removed specimen is an abnormal parathyroid. MATERIAL AND METHOD: 92 patients underwent CMI RG--HPP with PGC after the administration of a dose of 99 mTc-MIBI. The information provided by the PGC in the analysis of the excised specimens is qualitatively compared (capture yes/no) with the result of the intraoperative pathological anatomy (APio). The Gold standard is the definitive histology. RESULTS: 120 excised pieces are evaluated with GGio and APio. There were 110 agreements (95TP and 15TN) and 10 disagreements (3FP and 7FN). Of the 120 lesions, 102 were parathyroid and 18 were non-parathyroid. There was good agreement between intraoperative scintigraphy imaging (GGio) and PA, 70.1% according to Cohen's Kappa index. The GGio presented the following values ​​of Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, Positive Likelihood Ratio, Negative Likelihood Ratio and Overall Value of the Test (93.1%, 83.3%, 96.9%, 68.2%, 5.59, 0.08 and 0.92 respectively). CONCLUSION: GGio is a rapid and effective surgical aid technique to confirm/rule out the possible parathyroid nature of the lesions removed in PPH surgery, but it cannot replace histological study.

Direct radiolabeling of Folate with Tc-99m using QbD approach: A step closer to folate based diagnostic agent.

The aim of the presented work was to develop folate based radiolabeled compound intended to be used as diagnostic aid for the various folate-receptor overexpressing cancers eg. breast cancer, brain tumors, lung cancer etc. Folate was directly radiolabeled with Tc-99m using Quality-by-Design and encapsulated in micellar nanocarriers. The authors are of the view that the stable radiolabeled folate could be of potential diagnostic value in cancers overexpressing folate receptors thereby opening novel possibilities to diagnostic applications of radiolabeled folate. SUMMARY FOR TECHNICAL NOTES: Folic acid was directly radiolabeled with Tc-99m utilizing a quality by design approach. The experimental trials were designed using the Box-Behenken design with the concentration of drug, concentration of reducing agent and the incubation time as dependent variable and percent radiolabeling as the response for the same. The applied design in the method section was validated with a series of experiments and the percent labeling of the FA with Tc-99m was found to be around 94%. The radiolabeled compound was imperilled to stability evaluation by incubating the same with serum and physiological pH and the same was found to be stable at the end of 4h. On subjecting to DTPA challenge test, the compound displayed no change in the radiolabeling percentage thereby indicating the robustness of the formed Tc-99m-FA complex, The radiolabeled Tc-99m-FA was further encapsulated into micellar nanocarriers and the same were also found to be robust and stable.