Search

The coronavirus infection presents primarily as a respiratory illness, however, extra-pulmonary manifestations are known to occur, including gastrointestinal manifestations. Hereby, we report three cases of the COVID-19 infection who presented with acute-onset abdominal pain during illness. All three patients had respiratory symptoms suggestive of COVID-19 and abdominal symptoms consistent with acute pancreatitis, acute cholecystitis, and acute appendicitis. All three patients improved in terms of acute abdominal pain; however, the overall clinical course, the three illnesses were variable because of differences in underlying organ involment and pathophysiology., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped, positive sense, single stranded RNA (+ssRNA) virus, belonging to the genus Betacoronavirus and family Coronaviridae. It is primarily transmitted from infected persons to healthy ones through inhalation of virus-laden respiratory droplets. After an average incubation period of 2-14 days, the majority of infected individuals remain asymptomatic and/or mildly symptomatic, whereas the remaining individuals manifest a myriad of clinical symptoms, including fever, sore throat, dry cough, fatigue, chest pain, and breathlessness. SARS-CoV-2 exploits the angiotensin converting enzyme 2 (ACE-2) receptor for cellular invasion, and lungs are amongst the most adversely affected organs in the body. Thereupon, immune responses are elicited, which may devolve into a cytokine storm characterized by enhanced secretion of multitude of inflammatory cytokines/chemokines and growth factors, such as interleukin (IL)-2, IL-6, IL-7, IL-8, IL-9, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (GCSF), basic fibroblast growth factor 2 (bFGF2), monocyte chemotactic protein-1 (MCP1), interferon-inducible protein 10 (IP10), macrophage inflammatory protein 1A (MIP1A), platelet-derived growth factor subunit B (PDGFB), and vascular endothelial factor (VEGF)-A. The systemic persistence of inflammatory molecules causes widespread histological injury, leading to functional deterioration of the infected organ(s). Although multiple treatment modalities with varying effectiveness are being employed, nevertheless, there is no curative COVID-19 therapy available to date. In this regard, one plausible supportive therapeutic modality may involve administration of mesenchymal stem cells (MSCs) and/or MSC-derived bioactive factors-based secretome to critically ill COVID-19 patients with the intention of accomplishing better clinical outcome owing to their empirically established beneficial effects. MSCs are well established adult stem cells (ASCs) with respect to their immunomodulatory, anti-inflammatory, anti-oxidative, anti-apoptotic, pro-angiogenic, and pro-regenerative properties. The immunomodulatory capabilities of MSCs are not constitutive but rather are highly dependent on a holistic niche. Following intravenous infusion, MSCs are known to undergo considerable histological trapping in the lungs and, therefore, become well positioned to directly engage with lung infiltrating immune cells, and thereby mitigate excessive inflammation and reverse/regenerate damaged alveolar epithelial cells and associated tissue post SARS-CoV-2 infection. Considering the myriad of abovementioned biologically beneficial properties and emerging translational insights, MSCs may be used as potential supportive therapy to counteract cytokine storms and reduce disease severity, thereby facilitating speedy recovery and health restoration.

Piper betle L. (synonym: Piper betel Blanco), or betel vine, an economically and medicinally important cash crop, belongs to the family Piperaceae, often known as the green gold. The plant can be found all over the world and is cultivatedprimarily in South East Asian countries for its beautiful glossy heart-shaped leaves, which are chewed or consumed as betelquidand widely used in Chinese and Indian folk medicine, as carminative, stimulant,astringent, against parasitic worms, conjunctivitis, rheumatism, wound, etc., andis also used for religious purposes. Hydroxychavicol is the most important bioactive compound among the wide range of phytoconstituents found in essential oil and extracts. The pharmacological attributes of P. betle are antiproliferation, anticancer, neuropharmacological, analgesic, antioxidant, antiulcerogenic, hepatoprotective, antifertility, antibacterial, antifungal and many more. Immense attention has been paid to nanoformulations and their applications. The application of P. betle did not show cytotoxicity in preclinical experiments, suggesting that it could serve as a promising therapeutic candidate for different diseases. The present review comprehensively summarizes the botanical description, geographical distribution, economic value and cultivation, ethnobotanical uses, preclinical pharmacological properties with insights of toxicological, clinical efficacy, and safety of P. betle. The findings suggest that P. betle represents an orally active and safe natural agent that exhibits great therapeutic potential for managing various human medical conditions. However, further research is needed to elucidate its underlying molecular mechanisms of action, clinical aspects, structure-activity relationships, bioavailability and synergistic interactions with other drugs., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The effect of the self-focusing of a laser on second-harmonic generation (SHG) induced by the surface plasma waves (SPW) over the metal-semiconductor interface has been investigated. The nonlinear interactions of a laser with metal generate SPW. These high-amplitude waves could penetrate through plasmonic entities of metal and can interact with electrons of a semiconductor leading to SHG. The behavior of the beam width parameter for different metals has been analyzed. One may notice that the beam width parameter shows periodic variation with the distance, but the amplitude shows maxima in the regions of the low beam width parameter. The focusing accompanied by the increase in SHG amplitude is found to be better for the Cu-InSb interface as compared to the Ag-InSb and Al-InSb ones. The present work puts forward the metal-semiconductor interface as a good choice for SHG.

Camptothecin (CPT) is a monoterpenoid-alkaloid, an anticancer compound from plant. Ever since its discovery in 1996 from the bark of Camptotheca acuminata, various researches have been conducted for enhancing its production. CPT has also been reported in several other species belonging to the plant families Icacinaceae, Rubiaceae, Apocynaceae, Nyssaceae, Betulaceae, Violaceae, Meliaceae, and Gelseminaceae. Out of these, Ophiorrhiza sp. (Rubiaceae) is the next possible candidate for sustainable CPT production after C. acuminata and Nothapodytes nimoonia. Various biotechnological-studies have been conducted on Ophiorrhiza sp. for searching the elite species and the most optimal strategies for CPT production. The genus Ophiorrhiza has been used as medicines for antiviral, antifungal, antimalarial, and anticancer activities. Phytochemical analysis has revealed the presence of alkaloids, flavonoids, triterpenes, and CPT from the plant. Because of the presence of CPT and its herbaceous habit, Ophiorrhiza sp. has now become a hot topic in research area. Currently, for mass production of the elite spp., tissue culture techniques have been implemented. In the past decades, several researchers have contributed on the diversity assessment, phytochemical analysis, mass production, and in vitro production of CPT in Ophiorrhiza sp. In this paper, we review the on the biotechnological strategies, optimal culture medium, micropropagation of Ophiorrhiza sp., effect of PGR on shoot formation, rhizogenesis, callus formation, and enhanced production of CPT for commercial use. KEY POINTS: • Latest literature on in vitro propagation of Ophiorrhiza sp. • Biotechnological production of camptothecin and related compounds • Optimization, elicitation, and transgenic studies in Ophiorrhiza sp., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Over the last decade, remarkable progress has been made in our understanding the phytohormones, cytokinin's (CKs) biosynthesis, perception, and signalling pathways. Additionally, it became apparent that interfering with any of these steps has a significant effect on all stages of plant growth and development. As a result of their complex regulatory and cross-talk interactions with other hormones and signalling networks, they influence and control a wide range of biological activities, from cellular to organismal levels. In agriculture, CKs are extensively used for yield improvement and management because of their wide-ranging effects on plant growth, development and physiology. One of the primary targets in this regard is cytokinin oxidase/dehydrogenase (CKO/CKX), which is encoded by CKX gene, which catalyses the irreversible degradation of cytokinin. The previous studies on various agronomically important crops indicated that plant breeders have targeted CKX directly. In recent years, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been increasingly used in editing the CKO/CKX gene and phenomenal results have been achieved. This review provides an updated information on the applications of CRISPR-based gene-editing tools in manipulating cytokinin metabolism at the genetic level for yield improvement. Furthermore, we summarized the current developments of RNP-mediated DNA/transgene-free genomic editing of plants which would broaden the application of this technology. The current review will advance our understanding of cytokinins and their role in sustainably increase crop production through CRISPR/Cas genome editing tool., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mandal, Ghorai, Anand, Roy, Kant, Mishra, Mane, Jha, Lal, Tiwari, Kumar, Radha, Ghosh, Bhattacharjee, Proćków and Dey.)

Metastasis or the progression of malignancy poses a major challenge in cancer therapy and is the principal reason for increased mortality. The epithelial-mesenchymal transition (EMT) of the basement membrane (BM) allows cells of epithelial phenotype to transform into a mesenchymal-like (quasi-mesenchymal) phenotype and metastasize via the lymphovascular system through a metastatic cascade by intravasation and extravasation. This helps in the progression of carcinoma from the primary site to distant organs. Collagen, laminin, and integrin are the prime components of BM and help in tumor cell metastasis, which makes them ideal cancer drug targets. Further, recent studies have shown that collagen, laminin, and integrin can be used as a biomarker for metastatic cells. In this review, we have summarized the current knowledge of such therapeutics, which are either currently in preclinical or clinical stages and could be promising cancer therapeutics. DATA AVAILABILITY: Not applicable., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Bacopa monnieri (L.) Wettst. or water hyssop commonly known as "Brahmi" is a small, creeping, succulent herb from the Plantaginaceae family. It is popularly employed in Ayurvedic medicine as a nerve tonic to improve memory and cognition. Of late, this plant has been reported extensively for its pharmacologically active phyto-constituents. The main phytochemicals are brahmine, alkaloids, herpestine, and saponins. The saponins include bacoside A, bacoside B, and betulic acid. Investigation into the pharmacological effect of this plant has thrived lately, encouraging its neuroprotective and memory supporting capacity among others. Besides, it possesses many other therapeutic activities like antimicrobial, antioxidant, anti-inflammatory, gastroprotective properties, etc. Because of its multipurpose therapeutic potential, it is overexploited owing to the prioritization of natural remedies over conventional ones, which compels us to conserve them. B. monnieri is confronting the danger of extinction from its natural habitat as it is a major cultivated medico-botanical and seed propagation is restricted due to less seed availability and viability. The ever-increasing demand for the plant can be dealt with mass propagation through plant tissue culture strategy. Micropropagation utilizing axillary meristems as well as de novo organogenesis have been widely investigated in this plant which has also been explored for its conservation and production of different types of secondary metabolites. Diverse in vitro methods such as organogenesis, cell suspension, and callus cultures have been accounted for with the aim of production and/or enhancement of bacosides. Direct shoot-organogenesis was initiated in excised leaf and internodal explants without any exogenous plant growth regulator(s) (PGRs), and the induction rate was improved when exogenous cytokinins and other supplements were used. Moreover, biotechnological toolkits like Agrobacterium-mediated transformation and the use of mutagens have been reported. Besides, the molecular marker-based studies demonstrated the clonal fidelity among the natural and in vitro generated plantlets also elucidating the inherent diversity among the natural populations. Agrobacterium-mediated transformation system was mostly employed to optimize bacoside biosynthesis and heterologous expression of other genes. The present review aims at depicting the recent research outcomes of in vitro studies performed on B. monnieri which include root and shoot organogenesis, callus induction, somatic embryogenesis, production of secondary metabolites by in vitro propagation, acclimatization of the in vitro raised plantlets, genetic transformation, and molecular marker-based studies of clonal fidelity. KEY POINTS: • Critical and up to date records on in vitro propagation of Bacopa monnieri • In vitro propagation and elicitation of secondary metabolites from B. monnieri • Molecular markers and transgenic studies in B. monnieri., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The feasibility of cognitive rehabilitation is rarely investigated in patients with advanced multiple sclerosis., Methods: Eighteen patients with advanced multiple sclerosis (median EDSS = 7.5) were randomized into restorative or compensatory cognitive rehabilitation. Feasibility was determined by adherence rate, completion rate, patient satisfaction, self-reported fatigue, training difficulty, and training duration., Results: Adherence rates and completion rates were over 70%, and patients were highly satisfied in both groups. Energy levels decreased minimally during the sessions (pre = 6.9 vs post = 6.4). Training difficulty (4.6) and duration (5.7) were close to ideal (scale 1-10, 5 = ideal)., Conclusions: Cognitive rehabilitation, with minor adjustments, appears feasible in patients with advanced multiple sclerosis., Competing Interests: Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.E. Prouskas has nothing to disclose. N.D. Chiaravalloti has nothing to disclose. N. Kant has nothing to disclose. K.K. Ball holds stock in the Visual Awareness Research Group (formerly Visual Awareness, Inc.), and Posit Science, Inc., the companies that market the Useful Field of View Test and speed of processing training software. V. de Groot has nothing to disclose. B.M.J. Uitdehaag received compensation for consulting from Biogen, Genzyme, Merck Serono, Novartis, Roche, and Teva Pharmaceuticals. J.J.G. Geurts is an editor of MS journal and serves on the editorial boards of Neurology and Frontiers of Neurology and is president of the Netherlands organization for health research and innovation and has served as a consultant for Merck-Serono, Biogen, Novartis, Genzyme and Teva Pharmaceuticals. E.A. Kooij has nothing to disclose. H.E. Hulst serves on the editorial board of MSJ and has received compensation for consulting services or speaker honoraria from Sanofi Genzyme, Merck Serono and Biogen Idec., (© The Author(s), 2021.)

The first quarter of the 21st century has remarkably been characterized by a multitude of challenges confronting human society as a whole in terms of several outbreaks of infectious viral diseases, such as the 2003 severe acute respiratory syndrome (SARS), China; the 2009 influenza H1N1, Mexico; the 2012 Middle East respiratory syndrome (MERS), Saudi Arabia; and the ongoing coronavirus disease 19 (COVID-19), China. COVID-19, caused by SARS-CoV-2, reportedly broke out in December 2019, Wuhan, the capital of China's Hubei province, and continues unabated, leading to considerable devastation and death worldwide. The most common target organ of SARS-CoV-2 is the lungs, especially the bronchial and alveolar epithelial cells, culminating in acute respiratory distress syndrome (ARDS) in severe patients. Nevertheless, other tissues and organs are also known to be critically affected following infection, thereby complicating the overall aetiology and prognosis. Excluding H1N1, the SARS-CoV (also referred as SARS-CoV-1), MERS, and SARS-CoV-2 are collectively referred to as coronaviruses, and taxonomically placed under the realm Riboviria, order Nidovirales, suborder Cornidovirineae, family Coronaviridae, subfamily Orthocoronavirinae , genus Betacoronavirus , and subgenus Sarbecovirus . As of 23 September 2021, the ongoing SARS-CoV-2 pandemic has globally resulted in around 229 million and 4.7 million reported infections and deaths, respectively, apart from causing huge psychosomatic debilitation, academic loss, and deep economic recession. Such an unprecedented pandemic has compelled researchers, especially epidemiologists and immunologists, to search for SARS-CoV-2-associated potential immunogenic molecules to develop a vaccine as an immediate prophylactic measure. Amongst multiple structural and non-structural proteins, the homotrimeric spike (S) glycoprotein has been empirically found as the most suitable candidate for vaccine development owing to its immense immunogenic potential, which makes it capable of eliciting both humoral and cell-mediated immune responses. As a consequence, it has become possible to design appropriate, safe, and effective vaccines, apart from related therapeutic agents, to reduce both morbidity and mortality. As of 23 September 2021, four vaccines, namely, Comirnaty, COVID-19 vaccine Janssen, Spikevax, and Vaxzevria, have received the European Medicines Agency's (EMA) approval, and around thirty are under the phase three clinical trial with emergency authorization by the vaccine-developing country-specific National Regulatory Authority (NRA). In addition, 100-150 vaccines are under various phases of pre-clinical and clinical trials. The mainstay of global vaccination is to introduce herd immunity, which would protect the majority of the population, including immunocompromised individuals, from infection and disease. Here, we primarily discuss category-wise vaccine development, their respective advantages and disadvantages, associated efficiency and potential safety aspects, antigenicity of SARS-CoV-2 structural proteins and immune responses to them along with the emergence of SARS-CoV-2 VOC, and the urgent need of achieving herd immunity to contain the pandemic.

This was a first-in-human study of the PET radiotracer 11 C-LSN3172176 for the muscarinic acetylcholine receptor subtype M1. The objectives of the study were to determine the appropriate kinetic model to quantify binding of the tracer to M1 receptors, and the reliability of the chosen quantification method. Methods: Six healthy subjects completed the test-retest protocol, and 5 healthy subjects completed the baseline-scopolamine blocking protocol. Multiple modeling methods were applied to calculate total distribution volume ( V T ) and nondisplaceable binding potential ( BP ND ) in various brain regions. The reference region was selected from the blocking study. The occupancy plot was applied to compute receptor occupancy by scopolamine and nondisplaceable distribution volume. Results: Tracer uptake was highest in the striatum, followed by neocortical regions and white matter, and lowest in the cerebellum. Regional time-activity curves were fitted well by all models. The 2-tissue-compartment (2TC) model fits were good, but the 2TC parameters often could not be reliably estimated. Because V T correlated well between the 2TC and 1-tissue-compartment (1TC) models after exclusion of unreliable estimates, the 1TC model was chosen as the most appropriate. The cerebellum showed the lowest V T , consistent with preclinical studies showing little to no specific binding in the region. Further, cerebellar V T did not change between baseline and blocking scans, indicating that the cerebellum is a suitable reference region. The simplified reference tissue model (SRTM) slightly underestimated 1TC BP ND , and the simplified reference tissue model 2 (SRTM2) improved BP ND estimation. An 80-min scan was sufficient to quantify V T and BP ND The test-retest study showed excellent absolute test-retest variability for 1TC V T (≤5%) and BP ND (≤10%). In the baseline and blocking studies, occupancy values were lower in the striatum than in nonstriatal regions, as may be attributed to differences in regional acetylcholine concentrations. Conclusion: The 1TC and SRTM2 models are appropriate for quantitative analysis of 11 C-LSN3172176 imaging data. 11 C-LSN3172176 displayed excellent test-retest reproducibility and is a highly promising ligand to quantify M1 receptors in the human brain., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Previous studies found that [ 18 F]LSN3316612 was a promising positron emission tomography (PET) radioligand for imaging O-GlcNAcase in nonhuman primates and human volunteers. This study sought to further evaluate the suitability of [ 18 F]LSN3316612 for human clinical research., Methods: Kinetic evaluation of [ 18 F]LSN3316612 was conducted in a combined set of baseline brain scans from 17 healthy human volunteers and test-retest imaging was conducted in 10 of these volunteers; another 6 volunteers had whole-body scans to measure radiation exposure to body organs. Total distribution volume (V T ) estimates were compared for the one- and two-tissue compartment models with the arterial input function. Test-retest variability and reliability were evaluated via mean difference and intraclass correlation coefficient (ICC). The time stability of V T was assessed down to a 30-min scan time. An alternative quantification method for [ 18 F]LSN3316612 binding without blood was also investigated to assess the possibility of eliminating arterial sampling., Results: Brain uptake was generally high and could be quantified as V T with excellent identifiability using the two-tissue compartment model. [ 18 F]LSN3316612 exhibited good absolute test-retest variability (12.5%), but the arithmetic test-retest variability was far from 0 (11.3%), reflecting a near-uniform increase of V T on the retest scan in nine of 10 volunteers. V T values were stable after 110 min in all brain regions, suggesting that no radiometabolites accumulated in the brain. Measurements obtained using only brain activity (i.e., area under the curve (AUC) from 150-180 min) correlated strongly with regional V T values during test-retest conditions (R 2 = 0.84), exhibiting similar reliability to V T (ICC = 0.68 vs. 0.64). Estimated radiation exposure for [ 18 F]LSN3316612 PET was 20.5 ± 2.1 μSv/MBq, comparable to other 18 F-labeled radioligands for brain imaging., Conclusions: [ 18 F]LSN3316612 is an excellent PET radioligand for imaging O-GlcNAcase in the human brain. Alternative quantification without blood is possible, at least for within-subject repeat studies. However, the unexplained increase of V T under retest conditions requires further investigation.

The M 1 muscarinic acetylcholine receptor (mAChR) plays an important role in learning and memory, and therefore is a target for development of drugs for treatment of cognitive impairments in Alzheimer disease and schizophrenia. The availability of M 1 -selective radiotracers for PET will help in developing therapeutic agents by providing an imaging tool for assessment of drug dose-receptor occupancy relationship. Here we report the synthesis and evaluation of 11 C-LSN3172176 (ethyl 4-(6-(methyl- 11 C )-2-oxoindolin-1-yl)-[1,4'-bipiperidine]-1'-carboxylate) in nonhuman primates. Methods: 11 C-LSN3172176 was radiolabeled via the Suzuki-Miyaura cross-coupling method. PET scans in rhesus macaques were acquired for 2 h with arterial blood sampling and metabolite analysis to measure the input function. Blocking scans with scopolamine (50 μg/kg) and the M 1 -selective agent AZD6088 (0.67 and 2 mg/kg) were obtained to assess tracer binding specificity and selectivity. Regional brain time-activity curves were analyzed with the 1-tissue-compartment model and the multilinear analysis method (MA1) to calculate regional distribution volume. Nondisplaceable binding potential values were calculated using the cerebellum as a reference region. Results: 11 C-LSN3172176 was synthesized with greater than 99% radiochemical purity and high molar activity. In rhesus monkeys, 11 C-LSN3172176 metabolized rapidly (29% ± 6% parent remaining at 15 min) and displayed fast kinetics and extremely high uptake in the brain. Imaging data were modeled well with the 1-tissue-compartment model and MA1 methods. MA1-derived distribution volume values were high (range, 10-81 mL/cm 3 ) in all known M 1 mAChR-rich brain regions. Pretreatment with scopolamine and AZD6088 significantly reduced the brain uptake of 11 C-LSN3172176, thus demonstrating its binding specificity and selectivity in vivo. The cerebellum appeared to be a suitable reference region for derivation of nondisplaceable binding potential, which ranged from 2.42 in the globus pallidus to 8.48 in the nucleus accumbens. Conclusion: 11 C-LSN3172176 exhibits excellent in vivo binding and imaging characteristics in nonhuman primates and appears to be the first appropriate radiotracer for PET imaging of human M 1 AChR., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Accumulation of hyperphosphorylated tau, a microtubule-associated protein, plays an important role in the progression of Alzheimer disease. Animal studies suggest that one strategy for treating Alzheimer disease and related tauopathies may be inhibition of O -GlcNAcase (OGA), which may subsequently decrease pathologic tau phosphorylation. Here, we report the pharmacokinetics of a novel PET radioligand, 18 F-LSN3316612, which binds with high affinity and selectivity to OGA. Methods: PET imaging was performed on rhesus monkeys at baseline and after administration of either thiamet-G, a potent OGA inhibitor, or nonradioactive LSN3316612. The density of the enzyme was calculated as distribution volume using a 2-tissue-compartment model and serial concentrations of parent radioligand in arterial plasma. The radiation burden for future studies was based on whole-body imaging of monkeys. Oga ∆Br , a mouse brain-specific knockout of Oga, was also scanned to assess the specificity of the radioligand for its target enzyme. Results: Uptake of radioactivity in monkey brain was high (∼5 SUV) and followed by slow washout. The highest uptake was in the amygdala, followed by striatum and hippocampus. Pretreatment with thiamet-G or nonradioactive LSN3316612 reduced brain uptake to a low and uniform concentration in all regions, corresponding to an approximately 90% decrease in distribution volume. Whole-body imaging of rhesus monkeys showed high uptake in kidney, spleen, liver, and testes. In Oga ∆Br mice, brain uptake of 18 F-LSN3316612 was reduced by 82% compared with control mice. Peripheral organs were unaffected in Oga ∆Br mice, consistent with loss of OGA expression exclusively in the brain. The effective dose of 18 F-LSN3316612 in humans was calculated to be 22 μSv/MBq, which is typical for 18 F-labeled radioligands. Conclusion: These results show that 18 F-LSN3316612 is an excellent radioligand for imaging and quantifying OGA in rhesus monkeys and mice. On the basis of these data, 18 F-LSN3316612 merits evaluation in humans., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: India has the largest Buffalo population in the world, with every household in rural India owning buffaloes depending upon daily milk requirement - dairy farmers can own between 10 to 70 buffaloes. The health of Indian buffaloes is of economic importance since India is one of the largest buffalo meat exporters in the world, and Indian Buffalo semen is sold in the USA for breeding purposes. However, National Control Program on brucellosis is only active in South India and in Panjab (a North Indian state with high human brucellosis incidence). Our aim was to assess the knowledge and practices of the buffalo keepers of Delhi that make them susceptible to brucellosis., Results: Amongst all the 11 districts of Delhi, there was 0% awareness about brucellosis and also about the S19 vaccine as the buffalo keepers had never heard of S19 vaccine which is available at minimal cost from Indian Veterinary Research Institute, Bareilly, India. Majority of the respondents drink raw milk, sleep in cattle sheds, do not isolate sick cattle, do not test buffaloes blood for any disease before purchasing them, apply intrauterine medication with bare hands to buffalo after abortion of foetus, never clean their cattle sheds with a disinfectant and believe that they can only acquire skin infections from cattle. All of these habits make them prone to brucellosis. While about 20 to 27% of respondents reported a history of abortions and retained placenta, disposed of the placenta with bare hands, and applied raw milk on cracked lips. It was surprising to note that majority of them never reared small ruminants like sheep and goat with buffaloes or Bos species as they were aware of the rapid spread of disease from small to big ruminants., Conclusions: We found that buffalo keepers were ignorant of brucellosis, its causative agent, relevant vaccines and that they also involved in high-risk activities. As such, our findings highlight a need for buffalo keepers to be better educated via several awareness camps to minimize human exposure to Brucella in Delhi.

Objective: To examine whether hypoesthesia and chronic pain are related in patients with MS., Methods: Sixty-seven MS patients with pain and 80 persons without MS were included. Sensory functioning was tested by bedside neurological examination. Touch, joint position (dorsal column-medial lemniscus pathway), temperature sense, and pain (spinothalamic tract) were tested. Pain intensity was measured by the Colored Analogue Scale (CAS Intensity) and the Faces Pain Scale (FPS); pain affect was also measured by CAS Affect and Number of Words Chosen-Affective (NWC-A). Mood was assessed with the SCL-90 anxiety and depression subscales and the Beck Depression Inventory (BDI)., Results: A significant negative relationship was found between pain intensity and the function of the dorsal column-medial lemniscal pathway, but not with the spinothalamic tract., Conclusion: In addition to the already known relation between hyperesthesia and pain, hypoesthesia for touch and joint position also seems to be related to chronic pain in MS patients.

Objectives: In complex real life situations, memories for temporal and spatial information are naturally linked since sequential events coincide in time and space. Whether this connection is inseparable or instead whether these processes are functionally dissociable was investigated in this patient study., Methods: Spatial object-location and temporal order memory tasks were administered to 36 stroke patients and 44 healthy control participants., Results: On group level, patients with a stroke in the left hemisphere performed worse on temporal order memory, compared to the control participants. On individual level, using a multiple case-study approach, a clear pattern of dissociations was found between memory for temporal and for spatial features., Conclusions: These findings indicate that location and temporal order memory contain functionally separable processes. This adds to our understanding of how context information is processed in human memory. (JINS, 2017, 23, 421-430).

Indoor air pollution with harmful particulate matter (PM) is mainly caused by cigarette smoke. Super-Slim-Size-Cigarettes (SSL) are considered a less harmful alternative to King-Size-Cigarettes (KSC) due to longer filters and relatively low contents. We ask if "Combined Mainstream and Sidestream Smoke" (CMSS)-associated PM levels of SSL are lower than of KSC and thus are potentially less harmful. PM concentrations in CMSS (PM10, PM2.5, and PM₁) are measured from four cigarette types of the brand Vogue, using an "automatic-environmental-tobacco-smoke-emitter" (AETSE) and laser aerosol spectrometry: SSL-BLEUE, -MENTHE, -LILAS and KSC-La Cigarette and -3R4F reference. This analysis shows that SSL MENTHE emitted the highest amount of PM, and KSC-La Cigarette the lowest. 3R4F reference emitted PM in the middle range, exceeding SSL BLEUE and falling slightly below SSL LILAS. It emerged that PM₁ constituted the biggest proportion of PM emission. The outcome shows significant type-specific differences for emitted PM concentrations. Our results indicate that SSL are potentially more harmful for passive smokers than the respective KSC. However, this study cannot give precise statements about the general influence of the size of a cigarette on PM. Alarming is that PM₁ is responsible for the biggest proportion of PM pollution, since smaller particles cause more harmful effects.

Objectives: Prior research suggests that dampening neural activity of the intact, presumably overactive hemisphere, combined with increasing neural activity in the damaged hemisphere, might restore cortical interhemispheric balance and reduce neglect. In the present study we repeatedly applied a relatively new technique, transcranial direct current stimulation (tDCS), to the posterior parietal cortex to modulate spontaneous neural activity levels in a polarity dependent fashion to find evidence for improvements in severe hemispatial neglect in chronic patients., Methods: Eighty-nine patients were initially identified from our databases as having neglect, after thoroughly screening databases, consulting medical practitioners and baseline testing, only five met our inclusion criteria and agreed to participate. Sixty-five patients were excluded as they did not meet safety criteria for tDCS (epilepsy, metal implants), suffered from other medical conditions (i.e., heart disease, epilepsy, current psychiatric disorder) or displayed only mild neglect at baseline testing. Five patients with severe chronic hemispatial neglect were enrolled in a double-blind, placebo-controlled treatment program. TDCS or placebo was applied for 20 minutes over the left (cathodal) and right (anodal) posterior parietal cortex at an intensity of 2 mA on five consecutive days. Treatment conditions were separated by a four week wash-out period. Baseline corrected change in performance on the conventional subtests of the Behavioral Inattention Test (BIT) was our primary endpoint., Results: No treatment-related effects were observed for the BIT change scores and performance on individual subtests. Moreover, patients' performance somewhat improved only during the stimulation period (day one vs day five, irrespective of whether it was placebo or tDCS), but not thirty days later, indicating a practice effect., Discussion: The present study does not provide evidence that tDCS to the posterior parietal cortex improves chronic hemispatial neglect. As a result of in- and exclusion health and safety criteria the majority of patients were excluded, which indicates that performing large randomized controlled trials is not feasible in chronic neglect patients., (Copyright © 2015. Published by Elsevier Ltd.)

Introduction: Prospective memory is the ability to remember actions to be performed later in time or when a certain event occurs. Multiple cognitive processes are involved in prospective memory, and the degree to which automatic or effortful processes are involved may differ for different types of prospective memory tasks. This study aimed to investigate prospective memory (dys)functioning in stroke patients, and to get more insight in which cognitive processes are involved in time- versus event-based prospective memory., Methods: We investigated 39 community-dwelling stroke survivors and 53 matched control participants. Assessment included naturalistic and experimental event- and time-based prospective memory tasks, as well as standard neuropsychological measures of (retrospective) memory, processing speed and attention/executive functioning., Results: 41% of the stroke patients performed significantly worse than control participants on prospective memory tasks. Deficits in prospective memory occurred as frequently as impairments in retrospective memory (33%, χ(2)(1, N=39)=3.4, p=.066), and more often than impairments in attention/executive functioning (15%, χ(2)(1, N=39)=5.2, p=.022) and speed of processing (23%, χ(2)(1, N=39)=6.5, p=.011). Regression analyses showed that event-based ('focal') prospective memory is supported by retrospective memory, indicating that it is a relatively simple and automatic process. Time-based (non-'focal') prospective memory proved to be a more complex process, requiring active monitoring of the environment. Performance was predicted by speed of processing, attention/executive functioning and retrospective memory. Thirteen percent of the patients suffered from selective prospective memory impairment, which was associated with damage to the superior temporal gyrus., Conclusions: Impairment of prospective memory occurs frequently after stroke. Different cognitive operations are involved in distinct types of prospective memory. Results fit within the multi-process framework of prospective memory and help further specify its contents., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to measure the prevalence of navigation problems in patients with mild stroke, using a navigation questionnaire (the Wayfinding Questionnaire; WQ). In addition, the correlations between WQ scores and quality of life measures and neuropsychological test scores were studied., Methods: A sample of 62 patients with mild stroke completed a questionnaire measuring self-reported navigation ability and spatial anxiety. A subset of this sample (n = 31) also completed a questionnaire on quality of life. Additional relevant neuropsychological data were retrieved from medical files and correlated with WQ and quality of life scores., Results: The results indicate that self-reported navigation impairment occurs in a substantial proportion of patients (29.0%), compared with a large control group (n = 384) of which 19.9% showed impairment. Moreover, these ratings are closely linked to quality of life and negatively correlated with spatial anxiety. The neuro-psychological data show that there is very little correlation between scores on commonly administered tests and navigation ability, which is in line with the results of a previous study., Conclusion: As our data indicate that navigation impairment is common among patients with mild stroke, we recommend a specific focus on navigation ability as part of neuropsychological assessment. This focus is currently lacking. Furthermore, the use of dedicated, experimental navigation tests in cases of explicit problems with navigation should be considered, in order objectively to measure such impairments.

Prospective memory (PM) is the ability to remember to execute delayed intentions. Previous studies indicate that PM is impaired in persons with mild cognitive impairment (MCI) and dementia, but the extent, nature, and cognitive correlates are unclear. A meta-analytic review was, therefore, performed (literature search 1990 to July 2011) on case-control studies on PM in dementia (10 studies, 336 patients, 505 controls) and MCI (7 studies, 225 patients, 253 controls). Differences between event-based and time-based PM and between measures of prospective and retrospective memory were examined, as well as correlations with other cognitive functions. Results showed that patients with dementia or MCI exhibit large deficits in PM (Hedges' d -1.62 [95% confidence interval -1.98 to -1.27; p < .0001] for dementia; -1.24 [-1.51 to -0.995; p < .0001] for MCI; difference dementia vs. MCI: QM = 1.94, p = .16). Impairments were comparable in size for event-based and time-based PM (p > .05), as well as for prospective and retrospective memory (p > .05). PM showed modest correlations with measures of retrospective memory (median r = 0.27) and executive functioning (median r = 0.30). PM appears a valid construct in neuropsychological assessment in patients with dementia or MCI, but more insight is needed in the optimal characteristics of PM tasks to be used in clinical practice.

We present two cases (A.C. and W.J.) with navigation problems resulting from parieto-occipital right hemisphere damage. For both the cases, performance on the neuropsychological tests did not indicate specific impairments in spatial processing, despite severe subjective complaints of spatial disorientation. Various aspects of navigation were tested in a new virtual reality task, the Virtual Tübingen task. A double dissociation between spatial and temporal deficits was found; A.C. was impaired in route ordering, a temporal test, whereas W.J. was impaired in scene recognition and route continuation, which are spatial in nature. These findings offer important insights in the functional and neural architecture of navigation.

The authors present the first case of a primary yolk sac tumor of the neck metastasizing to the spine, demonstrated by computed tomography. It caused a partial block.