Search results for: spinal trigeminal nucleus

Authors: Jiang Xu, Daoping Wang, Yinghong Pan

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The jointing-booting stage is a critical period of both vegetative growth and reproductive growth in rice. Therefore, the proteomic analysis of the mutant Osbri1, whose corresponding gene OsBRI1 encodes the putative BRs receptor OsBRI1, at jointing-booting stage is very important for understanding the effects of BRs on vegetative and reproductive growth. In this study, the proteomes of leaves from an allelic mutant of the DWARF 61 (D61, OsBRI1) gene, Fn189 (dwarf54, d54) and its wild-type variety T65 (Taichung 65) at jointing-booting stage were analysed by using a Q Exactive plus orbitrap mass spectrometer, and more than 3,100 proteins were identified in each sample. Ontology analysis showed that these proteins distribute in various space of the cells, such as the chloroplast, mitochondrion, and nucleus, they functioned as structural components and/or catalytic enzymes and involved in many physiological processes. Moreover, quantitative analysis displayed that 266 proteins were differentially expressed in two samples, among them, 77 proteins decreased and 189 increased more than two times in Fn189 compared with T65, the proteins whose content decreased in Fn189 including b5-like Heme/Steroid binding domain containing protein, putative retrotransposon protein, putative glutaminyl-tRNA synthetase, and higher content proteins such as mTERF, putative Oligopeptidase homologue, zinc knuckle protein, and so on. A former study founded that the transcription level of a mTERF was up-regulated in the leaves of maize seedling after EBR treatment. In our experiments, it was interesting that one mTERF protein increased, but another mTERF decreased in leaves of Fn189 at jointing-booting stage, which suggested that BRs may have differential regulation mechanisms on the expression of various mTERF proteins. The relationship between other differential proteins with BRs is still unclear, and the effects of BRs on rice protein contents and its regulation mechanisms still need further research.

Keywords: bri1 mutant, jointing-booting stage, proteomic analysis, rice

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Authors: Inosha Bimali, Shambhu P. Adhikari, Sumana Baidya, Nishchal R. Shakya

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Background: An earthquake of 7.8 magnitudes with an epicenter in Gorkha on 25th April 2015 and second earthquake of 6.5 magnitudes with an epicenter at Sindhupalchwok on 12th May 2015 struck the beautiful country of Nepal, killing more than 8,500 people and over 18,500 individuals were left injured with various forms of disabilities. Objectives: To explore number, type and level of disability among post earthquake victims. A door to door physiotherapy rehabilitation program will be conducted at the community level as a continuation of this study. Methods: A survey was carried out in the catchment area of Bahunepati and Manekharka outreach centers of Sindhupalchowk district and Gaurishankar outreach center of Dolakha district of Dhulikhel Hospital. Physical disability was identified using a disability survey form given by Ministry of women, children and social welfare Nepal Government. World health organization disability assessment schedule-2 was used to identify the level of disability. Results: Twenty-nine person with disabilities at Bahunepati, four person with disabilities at Manekharkha and two person with disabilities at Gaurishankar and its catchment area were identified. Level of disability was an average of 56% with majority of survivors having upper extremities fractures followed by lower extremities fractures and miscellaneous injury. Few spinal cord injuries and head injuries were also identified. Conclusion: Though number of person with disabilities was found relatively less, disability level is high; hence an urgent need of physiotherapy rehabilitation is reflected to improve the quality of life of the affected people.

Keywords: community, disability, Nepal earthquake, physiotherapy

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

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Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

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Authors: Alpana Meena

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Background: Tuberculosis is one of the major causes of death in south-east nations. Anti-TB–induced hepatotoxicity (AIH) is associated with a mortality of 6%–12%. The risk is increased when the drugs are combined. Reintroduction of anti-tuberculosis drugs in patients with AIH has never been studied systematically. The present study was planned to see the clinical profile of patients of AIH and the response to reintroduction of therapy. Methods: The trial was conducted in the Department of Medicine, Maulana Azad Medical College and associated Lok Nayak Hospital, on 32 patients with extra-pulmonary tuberculosis who developed AIH. Patients were randomly allocated into 3 groups. In group 1- Isoniazid (INH) and Rifampicin (RIF) were given at full dosages (weight calculated) from day 1. In group 2- RIF was given at maximum dosage from day 1 and INH at maximum dosage from day 8. In group 3- INH was given at maximum dosage from day 1 and RIF at maximum dosage from day 8. Pyrazinamide was added when above regimens were tolerated. Results: The mean age of presentation was 29.37±13.497 years. The incidence was found to be highest in patients with tubercular meningitis (41%) followed by abdominal, pericardial, disseminated, spinal, and lymph nodes. The mean latent period for development of AIH was 7.84 days ± 6.149 days and the median normalization days for LFT’s was 8.81 ± 4.22 days (3-21). In the study, 21% patients had recurrence of AIH with majority of patients having tolerated the reintroduction of drugs. Pyrazinamide was introduced after establishing isoniazid and rifampicin safety, thus emphasizing the role of gradual reintroduction of ATT to avoid the combined effects of hepatotoxicity. Conclusion: To conclude, the recurrence rate of hepatotoxicity was not statistically significant between the three groups studied (p > 0.05), and thus all 3 hepatotoxic drugs can be reintroduced safely in patients developing AIH.

Keywords: anti-tubercular therapy induced hepatotoxicity, extra-pulmonary tuberculosis, reintroduction regimens, risk factors

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Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

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Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

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Authors: Spyridon Komaitis, Christos Koutsarnakis, Evangelos Drosos, Aristotelis Kalyvas

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This study opts to investigate the intrinsic architecture, morphology, and spatial relationship of the subcortical pathways implicated in the connectivity of the motor/premotor cortex and SMA/pre-SMA complex. Twenty normal, adult, formalin-fixed cerebral hemispheres were explored through the fiber micro-dissection technique. Lateral to medial and medial to lateral dissections focused on the area of interest were performed in a tandem manner and under the surgical microscope. We traced the subcortical architecture, spatial relationships, and axonal connectivity of four major pathways: a) the dorsal component of the SLF (SLF-I) was found to reside in the medial aspect of the hemisphere and seen to connect the precuneus with the SMA and pre-SMA complex, b) the frontal longitudinal system (FLS) was consistently encountered as the natural anterior continuation of the SLF-II and SLF-III and connected the premotor and prefrontal cortices c) the fronto-caudate tract (FCT), a fan-shaped tract, was documented to participate in connectivity of the prefrontal and premotor cortices to the head and body of the caudate nucleus and d) the cortico-tegmental tract(CTT) was invariably recorded to subserve the connectivity of the tegmental area with the fronto-parietal cortex. No hemispheric asymmetries were recorded for any of the implicated pathways. Sub-segmentation systems were also proposed for each of the aforementioned tracts. The structural connectivity and functional specialization of motor and premotor areas in the human brain remain vague to this day as most of the available evidence derives either from animal or tractographic studies. By using the fiber-microdissection technique as our main method of investigation, we provide sound structural evidence on the delicate anatomy of the related white matter pathways.

Keywords: neuroanatomy, premotor, motor, connectivity

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Authors: Naghmeh Zamani, Ashkan Pourkand, David Grow

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This paper presents the design and mechanical model of a hybrid impedance/admittance haptic device optimized for applications, like bone drilling, spinal awl probe use, and other surgical techniques were high force is required in the tool-axial direction, and low impedance is needed in all other directions. The performance levels required cannot be satisfied by existing, off-the-shelf haptic devices. This design may allow critical improvements in simulator fidelity for surgery training. The device consists primarily of two low-mass (carbon fiber) plates with a rod passing through them. Collectively, the device provides 6 DOF. The rod slides through a bushing in the top plate and it is connected to the bottom plate with a universal joint, constrained to move in only 2 DOF, allowing axial torque display the user’s hand. The two parallel plates are actuated and located by means of four cables pulled by motors. The forward kinematic equations are derived to ensure that the plates orientation remains constant. The corresponding equations are solved using the Newton-Raphson method. The static force/torque equations are also presented. Finally, we present the predicted distribution of location error, cables velocity, cable tension, force and torque for the device. These results and preliminary hardware fabrication indicate that this design may provide a revolutionary approach for haptic display of many surgical procedures by means of an architecture that allows arbitrary workspace scaling. Scaling of the height and width can be scaled arbitrarily.

Keywords: cable direct driven robot, haptics, parallel plates, bone drilling

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Authors: Sushila Jaiswal, Awadhesh Kumar Jaiswal

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Background: Primary melanocytic tumors of the central nervous system (CNS) are uncommon lesions and arise from the melanocytes located within the leptomeninges. Aim and objective: The aim of the study was to evaluate the clinical details, histomorphology of the primary melanocytic tumor of CNS. Method: The study was performed by the retrospective review of the case records of the primary melanocytic tumors of CNS diagnosed in our department. The formalin-fixed, paraffin embedded tissue blocks and tissue sections were retrieved and reviewed. Results: Seven cases (6 males, 1 female; age range- 16-40 years; mean age- 27 years) of primary melanocytic tumors of CNS were retrieved over last seven years. The tumor was intracranial (n=5; frontal – 1 case, parietal – 1 case, cerebello-pontine angle- 1 case, occipital -1 case, foramen magnum-1 case) and intra spinal (n=2; cervical – 2 cases). All patients presented with the neurological deficits related to the location of the tumor. Four cases were malignant melanoma; two were melanocytoma of intermediate grade and remaining one was melanocytoma. On histopathology, melanocytoma and melanoma both displayed sheets of well-differentiated melanocytes having round to oval nuclei with finely dispersed chromatin, occasional single eosinophilic nucleoli and a moderate amount of cytoplasm with abundant granular melanin pigment. The absence of mitosis and macronucleoli was noticed in melanocytoma while melanoma showed frequent mitosis and macronucleoli. On immunohistochemistry, both showed diffuse strong HMB45 and S-100 immunopositivity. Conclusion: Primary melanocytic tumors of CNS are rare and predominantly seen in males. It is important to differentiate melanoma from melanocytoma as prognosis of later is good.

Keywords: melanocytoma, melanoma, brain tumor, melanin

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Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

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Authors: Ranjith Menon, Abathar Aladi, Hans-Christean Nahser, Maneesh Bhojak, Sacha Nevin, Paul Eldridge

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Background: Spontaneous subarachnoid haemorrhage (SAH) accounts for approximately 5% of all strokes. Patients with spontaneous SAH (as shown by CT or lumbar puncture) undergo investigations to identify or exclude an underlying structural cause, typically cerebral aneurysm. However in 10 - 20% of cases, no structural cause is found. This includes more than one imaging modality (intracranial MRA, CTA, 4DCTA and/or DSA) and in some spinal MRI. Objective: To determine; 1) If an underlying structural or vascular cause can be identified in non-aneurysmal SAH patients by comparing different imaging modalities at presentation and at follow-up. 2) If MRI spine in patients with non-aneurysmal SAH reveals an underlying SAH cause. 3)The functional outcome at discharge. Results: We performed a retrospective analysis of all non-traumatic SAH patients admitted to the Walton centre from January 2009 to December 2015. There were 1457 patients with non-traumatic SAH admitted to the Walton centre of whom 21.8% (n=300) patients were diagnosed with non-aneurysmal SAH. Males were 65.6% and females were 43.3%. The presenting symptoms were sudden onset headache (93.6%), the focal neurological deficit (12%), loss of consciousness (10.6%) and others (6%). About 285 patients received 2 modalities of imaging (CTA & DSA), 192 received 3 modalities of imaging (CTA, MRA & DSA) and 137 received MRI spine (51/137 whole spine). The modified Rankin Score at discharge were: mRS 0 = 292 (97.33%), mRS 1-2 = 6, mRS 6 = 1 (cardiac arrest in IHD patient) and unknown in 1. Follow-up imaging at 3 to 6 months in 190 (63.3%) patients did not identify an underlying cause. Conclusion: This retrospective analysis concludes that non-aneurysmal SAH has a good functional outcome. A single imaging modality (CTA (4DCTA) or MRA or DSA) was adequate to exclude an underlying cause of SAH and a delayed imaging failed to identify a cause. Routinely performing MRI spine in this group of patients appears not to be necessary according to this evidence.

Keywords: stroke, non-aneurysmal subarachnoid haemorrhage, neuroimaging, modified rankin score

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Authors: Vasishtha Avadhani Upadrasta, Mradul Kumar Daga, Smita Kaushik

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Background: Caffeine consumption has skyrocketed in the recent decades as we try to match pace with the machines. Studies have been conducted on animals and a few on humans, mainly on the acute effects of high-dose caffeine intake. Almost none have been conducted on the chronic effects of caffeine consumption. This study involved Medical professionals as case subjects, who consumed caffeine daily. Methods: This study, over a period of 3 months, involved 96 volunteers (chosen randomly w.r.t. gender and field in medical fraternity), including people who drank >500mg of caffeine a day to people who consumed none. People with any co-morbidities at all were excluded straight away. Two sets of blood samples were drawn and assessed. Three groups were created, Group 1 (>200mg caffeine/day) and Group 2 (15-200 mg caffeine/day) and Group 3 (<200mg Caffeine/day). Results: The result of the study found that exposure to caffeine at doses >200mg/day for more than 6 months leads to a significant difference in circulating free T3 [(-0.96 pmol/L ± 0.07) = (-18.5%), CI 95%, p = .000024] and Cortisol [(-123 nmol/L ± 9.8) = (-46.8%), CI 95%, p = .00029] hormones but shows an insignificant effect on circulating TSH [0.4 mIU/L, CI 95%, p=.37] and ACTH [(-3.2 pg/ml ± 0.3), CI 95%, p = .53) hormones, which stay within normal physiological ranges, irrespective of the daily dose of consumption. Results also highlight that women are more susceptible to decrement in fT3 than men (Relative Risk =1.58, ANOVA F-static = 7.15, p = 0.0105). Conclusions: Caffeine consumption in excess of 200mg/day, for more than or equal to 6 months, causes significant derangement in basal fT3 and Cortisol hormone levels, without affecting the TSH and ACTH (regulatory) hormone levels, indicating disturbance of action at the peripheral and/or cellular levels, possibly via the Paraventricular Nucleus –Leptin-CAR-Adenosine interactions. Women are more susceptible to decrement in fT3 levels than men (at same dose of caffeine).

Keywords: ACTH, adrenals, caffeine, cortisol, thyroid, thyroxin, TSH

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: R. Unnikrishnan, K. Shankar

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In the case of high-speed fighter aircrafts, seat ejection is designed mainly for the safety of the pilot in case of an emergency. Strong windblast due to the high velocity of flight is one main difficulty in clearing the tail of the aircraft. Excessive G-forces generated, immobilizes the pilot from escape. In most of the cases, seats are ejected out of the aircrafts by explosives or by rocket motors attached to the bottom of the seat. Ejection forces are primarily in the vertical direction with the objective of attaining the maximum possible velocity in a specified period of time. The safe ejection parameters are studied to estimate the critical time of ejection for various geometries and velocities of flight. An equivalent analytical 2-dimensional biomechanical model of the human spine has been modelled consisting of vertebrae and intervertebral discs with a lumped mass approach. The 24 vertebrae, which consists of the cervical, thoracic and lumbar regions, in addition to the head mass and the pelvis has been designed as 26 rigid structures and the intervertebral discs are assumed as 25 flexible joint structures. The rigid structures are modelled as mass elements and the flexible joints as spring and damper elements. Here, the motions are restricted only in the mid-sagittal plane to form a 26 degree of freedom system. The equations of motions are derived for translational movement of the spinal column. An ejection force with a linearly increasing acceleration profile is applied as vertical base excitation on to the pelvis. The dynamic vibrational response of each vertebra in time-domain is estimated.

Keywords: biomechanical model, lumped mass, seat ejection, vibrational response

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Authors: Khulood Zahran

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Background and Purpose: The effects of backpack on 'school-age' children (Age 9–12) years, have been a critical subject of discussion throughout the past years. It has been one of the factors that contribute to a bad posture for 40% to 70% of developed countries. A child carrying a heavy backpack for a prolonged period, on a daily base has shown significant changes in the child's spinal posture, foot shape, and gait. The back pain caused by the compensatory posture, or "Backpack syndrome", is also known for its headaches, fatigue, cervical and lumber pain caused by the abnormal body posture. The child tends to balance himself by bending forward to match the heavy backpack, moving his Centre of Gravity forward, resulting in decreased lumber lordosis and increased thoracic kyphosis. Since currently available bags have not addressed the weight distribution issue till now. Therefore, KZ bag is believed to prevent the huge backward shift of COG due to the load, and hence all the symptoms accompanied. This is thought to be possible by combining the design of a normal backpack with a messenger bag. The purpose of this study is to investigate the improvement of the child's spine and to minimize the compensatory posture after using the KZ bag. Materials and Methods: KZ bag would compromise the pros of a messenger bag (keeping the COG in place) by a diagonal load strap and of a backpack (distributing the load on both shoulders) by connecting another load strap parallel to the sagittal plane of the body. The design would be made adjustable to match the child's height, and the bag load kept within limits, (10-15%) of the child's body weight. Measurements of Postural angles (Cervical, shoulders, and Trunk) would be taken after the use of KZ bag for a specified period. Conclusion: KZ bag will prove an improved distribution of weight of the bag on the child's body, and reduce the degree of the compensatory posture, that occurs in the attempt to balance the external weight of the bag.

Keywords: backpack, backpack syndrome, posture, spine

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Authors: Jaydip De

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Urban parks are open places, green fields and riverside gardens usually maintained by public or private authorities, or eventually by both jointly; and utilized for a multidimensional purpose by the citizens. These parks are indeed the lung of urban centers. In urban socio-environmental setup, parks are the nucleus of social integration, community building, and physical development. In contemporary cities, these green places seem to perform as the panacea of congested, complex and stressful urban life. The alarmingly increasing urban population and the resultant congestion of high-rises are making life wearisome in neo-liberal cities. This has made the citizen always quest for open space and fresh air. In such a circumstance, the mere existence of parks is not capable of satisfying the growing aspirations. Therefore in this endeavour, a structured attempt is so made to empirically identify the utility, visitors’ satisfaction, and future needs through the cases of two urban parks of Kolkata Metropolitan Area, India. This study is principally based upon primary information collected through visitors’ perception survey conducted at the Chinsurah ground and Chandernagore strand. The correlation between different utility categories is identified and analyzed systematically. At the same time, indices like Weighted Satisfaction Score (WSS), Facility wise Satisfaction Index (FSI), Urban Park Satisfaction Index (UPSI) and Urban Park Necessity Index (UPNI) are advocated to quantify the visitors’ satisfaction and future necessities. It is explored that the most important utilities are passive in nature. Simultaneously, satisfaction levels of visitors are average, and their requirements are centred on the daily needs of the next generation, i.e., the children. Further, considering the visitors’ opinion planning measures are promulgated for holistic development of urban parks to revitalize sustainability of citified life.

Keywords: citified life, future needs, visitors’ satisfaction, urban parks, utility

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Authors: S. S. Singh, A. Bhattacharya, S. Bhattacharya

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The eukaryotic exosome complex plays a pivotal role in RNA biogenesis, maturation, surveillance and differential expression of various RNAs in response to varying environmental signals. The exosome is composed of evolutionary conserved nine core subunits and the associated exonucleases Rrp6 and Rrp44. Rrp6p is crucial for the processing of rRNAs, other non-coding RNAs, regulation of polyA tail length and termination of transcription. Rrp6p, a 3’-5’ exonuclease is required for degradation of 5’-external transcribed spacer (ETS) released from the rRNA precursors during the early steps of pre-rRNA processing. In the parasitic protist Entamoeba histolytica in response to growth stress, there occurs the accumulation of unprocessed pre-rRNA and 5’ ETS sub fragment. To understand the processes leading to this accumulation, we looked for Rrp6 and the exosome subunits in E. histolytica, by in silico approaches. Of the nine core exosomal subunits, seven had high percentage of sequence similarity with the yeast and human. The EhRrp6 homolog contained exoribonuclease and HRDC domains like yeast but its N- terminus lacked the PMC2NT domain. EhRrp6 complemented the temperature sensitive phenotype of yeast rrp6Δ cells suggesting conservation of biological activity. We showed 3’-5’ exoribonuclease activity of EhRrp6p with in vitro-synthesized appropriate RNAs substrates. Like the yeast enzyme, EhRrp6p degraded unstructured RNA, but could degrade the stem-loops slowly. Furthermore, immunolocalization revealed that EhRrp6 was nuclear-localized in normal cells but was diminished from nucleus during serum starvation, which could explain the accumulation of 5’ETS during stress. Our study shows functional conservation of EhRrp6p in E.histolytica, an early-branching eukaryote, and will help to understand the evolution of exosomal components and their regulatory function.

Keywords: entamoeba histolytica, exosome complex, rRNA processing, Rrp6

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Authors: Anca Dinischiotu, Sorina Nicoleta Voicu

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Silica nanoparticles (SiO2-NPs) are widely used in consumer products such as paints, plastics, insulation materials, tires, concrete production, as well as in gene delivery systems and imaging procedures. Environmental human exposure to them occurs during utilization of these products, in a time-dependent manner, the uptake being by topic and inhalation route especially. SiO2-NPs enter cells and induce membrane damage, oxidative stress and inflammatory reactions in a concentration-dependent manner. In this study, MRC-5 cells (human fetal lung fibroblasts) were exposed to amorphous SiO2-NPs at a dose of 62.5 μg/ml for 24, 48 and 72 hours. The size distribution of NPs was a lognormal function, in the range 3-14 nm. A time-dependent decrease of total reduced glutathione concentration by 36%, 50%, and 78% and an increase of NO level by 62%, 32%, respectively 24% compared to control were noticed. An up-regulation of NF-kB expression by 20%, 50% respectively 10% and of Nrf-2 by 139%, 58%, and 16% compared to control after 24, 48 and 72 hours was noticed also. The expression of IL-1β, IL-6, IL-8, and COX-2 was up-regulated in a time-dependent manner. Also, the expression of MMP-2 and MMP-9 were down-regulated after 48 and 72 hours, whereas their activities raised in a time-dependent manner. Exposure of cells to NPs up-regulated the expression of inducible NO synthase, as previously was shown, and probably this is the reason for the increased level of NO, that can react with the thiol groups of reduced glutathione molecules, diminishing its concentration Nrf2 is a transcription factor translocated in nucleus, under oxidative stress, where downstream gene expression activates in order to modulate the adaptive intracellular response against oxidative stress. The cross-talk between Nrf2 and NF-kB activities regulates the inflammatory processes. The activation of NF-kB could activate up-regulation of IL-1β, IL-6, and IL-8. The increase of COX-2 expression could be correlated with IL-1β one. Also, probably in response to the pro-inflammatory cytokines, MMP-2 and MMP-9 were induced and activated. In conclusion, the exposure of MRC-5 cells to SiO2-NPs generated inflammation in a time-dependent manner.

Keywords: inflammation, MRC-5 cells, oxidative stress, silica nanoparticles

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Authors: Hamed Karimian, Noraziah Nordin, Mohamad Ibrahim Noordin, Syam Mohan, Mahboubeh Razavi, Najihah Mohd Hashim, Happipah Mohd Ali

Abstract:

Satureja bachtiarica Bunge is a perennial medicinal plant belonging to the Lamiaceae family and endemic species in Iran. Satureja bachtiarica Bunge with the local name of Marzeh koohi is edible vegetable use as flavoring agent, anti-bacterial and to relieve cough and indigestion. In this study, the anti-cancer effect of Satureja bachtiarica Bunge on the MDA-MB-231 cell line as an Breast cancer cell model has been analyzed for the first time. Satureja bachtiarica Bunge was extracted using different solvents in the order of increasing polarity. Cytotoxicity activity of hexane extract of Satureja bachtiarica Bunge (SBHE) was observed using MTT assay. Acridine orange/Propidium iodide staining was used to detect early apoptosis; Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS), with Annexin-Vserving as a marker for apoptotic cells. Caspase 3/7, 8 and-9 assays showed significantly activation of caspase-9 where lead intrinsic mitochondrial pathway. Bcl-2/Bax expressions and cell cycle arrest were also investigated. SBHE had exhibited significantly higher cytotoxicity against MDA-MB-231 Cell line compare to other cell lines. A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Treatment of MDA-MB-231 cells with SBHE encouraged apoptosis, by down-regulating Bcl-2 and up-regulating Bax, which lead the activation of caspase 9. Moreover, SBHE treatment significantly arrested MDA-MB-231 cells in the G1 phase. Together, the results presented in this study demonstrated that SBHE inhibited the proliferation of MDA-MB-231 cells, leading cell cycle arrest and programmed cell death, which was confirmed to be through the mitochondrial pathway.

Keywords: Satureja bachtiarica Bunge, MDA-MB-231, apoptosis, annexin-V, cell cycle

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Authors: Atena Sadat Hosseini, Mohammadhossein Habibi

Abstract:

Acute myeloid leukemia (AML) is the most typically diagnosed leukemia. In older adults, AML imposes a dismal outcome. AML originates with a dominant mutation, then adds collaborative, transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Several chemotherapeutic drugs are used for this cancer. These drugs are naturally associated with several side effects, and finding a more accurate molecular mechanism of these drugs can have a significant impact on the selection and better candidate of drugs for treatment. In this study, we evaluated bortezomibin myeloma cells using bioinformatics analysis and evaluation of RNA-Seq data. Then investigated the molecular pathways proteins- proteins interactions associated with this chemotherapy drug. A total of 658upregulated genes and 548 downregulated genes were sorted.AUF1 (hnRNP D0) binds and destabilizes mRNA, degradation of GLI2 by the proteasome, the role of GTSE1 in G2/M progression after G2 checkpoint, TCF dependent signaling in response to WNT demonstrated in upregulated genes. Besides insulin resistance, AKT phosphorylates targets in the nucleus, cytosine methylation, Longevity regulating pathway, and Signal Transduction of S1P Receptor were related to low expression genes. With respect to this results, HIST2H2AA3, RP11-96O20.4, ZED9, PRDX1, and DOK2, according to node degrees and betweenness elements candidates from upregulated genes. in the opposite side, PYURF, NRSN1, FGF23, UPK3BL, and STAG3 were a prominent role in downregulated genes. Sum up, Using in silico analysis in the present study, we conducted a precise study ofbortezomib molecular mechanisms in myeloma cells. so that we could take further evaluation to discovermolecular cancer therapy. Naturally, more additional experimental and clinical procedures are needed in this survey.

Keywords: myeloma cells, acute myeloid leukemia, bioinformatics analysis, bortezomib

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Authors: Yong Chen

Abstract:

To understand the detailed molecular mechanisms of memory formation in engram cells is one of the most fundamental questions in neuroscience. Recent single-cell RNA-seq (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) techniques have allowed us to explore the sparsely activated engram ensembles, enabling access to the molecular mechanisms that underlie experience-dependent memory formation and consolidation. However, the absence of specific and powerful computational methods to detect memory-related genes (modules) and their regulatory relationships in the sc/snRNA-seq datasets has strictly limited the analysis of underlying mechanisms and memory coding principles in mammalian brains. Here, we present a deep-learning method named SCENTBOX, to detect memory-related gene modules and causal regulatory relationships among themfromsc/snRNA-seq datasets. SCENTBOX first constructs codifferential expression gene network (CEGN) from case versus control sc/snRNA-seq datasets. It then detects the highly correlated modules of differential expression genes (DEGs) in CEGN. The deep network embedding and attention-based convolutional neural network strategies are employed to precisely detect regulatory relationships among DEG genes in a module. We applied them on scRNA-seq datasets of TRAP; Ai14 mouse neurons with fear memory and detected not only known memory-related genes, but also the modules and potential causal regulations. Our results provided novel regulations within an interesting module, including Arc, Bdnf, Creb, Dusp1, Rgs4, and Btg2. Overall, our methods provide a general computational tool for processing sc/snRNA-seq data from case versus control studie and a systematic investigation of fear-memory-related gene modules.

Keywords: sc/snRNA-seq, memory formation, deep learning, gene module, causal inference

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Authors: Nitesh Kumar, Eoin Twohig, jasparl cheema, Sadiq mawji, Yousif al najjar

Abstract:

Basal cell carcinoma (BCC) is the commonest cutaneous malignancy affecting humans. Despite this, distant spread is exceptionally rare. Metastatic BCC (mBCC) is estimated to occur in 0.0028 - 0.5%. it aim to illustrate with the aid of histological slides, a case of mBCC occurring in a fit and well 67-year-old. Initial diagnosis of desmoplastic BCC was made in 2006 from a scalp biopsy with the lesion then being excised. Re-excision of local recurrence was undertaken the following year. In 2014 the patient presented with an ipsilateral level 2a mass. Fine Needle Aspiration raised the suspicion of metastatic carcinoma. The patient had excision of two nodes from the left neck alongside pharyngeal tonsillectomy and tongue base biopsies. Histologically, the nodes closely resembled the immunophenotype of the initial scalp lesion. The patient subsequently had a modified radical neck dissection, and residual mBCC was excised from the left Sternocleidomastoid muscle. In 2023 the patient developed haematuria. On further investigation bilateral lung lesions on CT were noted with subsequent biopsy confirming mBCC. Spinal and renal lesions have also been found. Histopathology showed clear resemblance of the lung metastases to both those in the neck and the primary (scalp BCC) – with no squamous differentiation seen. The time span from primary to occurrence of lung metastasis (18 years) affirms the indolent and slow growing nature of BCC.  This case fulfils Lattes and Kessler diagnostic criteria. High risk cases are described as those with advanced local presentation, primary tumour on the Head and Neck and locally recurrent lesions.

Keywords: BCC, metastasis, rare, skin cancer

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Authors: S. M. Ismail, H-H Yen, C. M. Murray, H. M. S. Davies

Abstract:

A recent study reported a 33% incidence of complete sacrocaudal fusion in greyhounds compared to a 3% incidence in other dogs. In the dog, the median sacral crest is formed by the fusion of sacral spinous processes. Separation of the 1st spinous process from the median crest of the sacrum in the dog has been reported as a diagnostic tool of type one lumbosacral transitional vertebra (LTV). LTV is a congenital spinal anomaly, which includes either sacralization of the caudal lumbar part or lumbarization of the most cranial sacral segment of the spine. In this study, the absence or reduction of fusion (presence of separation) between the 1st and 2ndspinous processes of the median sacral crest has been identified in association with sacrocaudal fusion in the greyhound, without any feature of LTV. In order to provide quantitative data on the absence or reduction of fusion in the median sacral crest between the 1st and 2nd sacral spinous processes, in association with sacrocaudal fusion. 204 dog sacrums free of any pathological changes (192 greyhound, 9 beagles and 3 labradors) were grouped based on the occurrence and types of fusion and the presence, absence, or reduction in the median sacral crest between the 1st and 2nd sacral spinous processes., Sacrums were described and classified as follows: F: Complete fusion (crest is present), N: Absence (fusion is absent), and R: Short crest (fusion reduced but not absent (reduction). The incidence of sacrocaudal fusion in the 204 sacrums: 57% of the sacrums were standard (3 vertebrae) and 43% were fused (4 vertebrae). Type of sacrum had a significant (p < .05) association with the absence and reduction of fusion between the 1st and 2nd sacral spinous processes of the median sacral crest. In the 108 greyhounds with standard sacrums (3 vertebrae) the percentages of F, N and R were 45% 23% and 23% respectively, while in the 84 fused (4 vertebrae) sacrums, the percentages of F, N and R were 3%, 87% and 10% respectively and these percentages were significantly different between standard (3 vertebrae) and fused (4 vertebrae) sacrums (p < .05). This indicates that absence of spinous process fusion in the median sacral crest was found in a large percentage of the greyhounds in this study and was found to be particularly prevalent in those with sacrocaudal fusion – therefore in this breed, at least, absence of sacral spinous process fusion may be unlikely to be associated with LTV.

Keywords: greyhound, median sacral crest, sacrocaudal fusion, sacral spinous process

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Authors: Alireza Pirkhaefi

Abstract:

Background: Multiple sclerosis (MS) is one of the most common diseases of the central nervous system (brain and spinal cord). Given the importance of cognitive disorders in patients with multiple sclerosis, the present study was in order to compare cognitive functions (Working memory, Attention and Centralization, and Visual-spatial perception) in patients with relapsing- remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Method: Present study was performed as a retrospective study. This research was conducted with Ex-Post Facto method. The samples of research consisted of 60 patients with multiple sclerosis (30 patients relapsing-retrograde and 30 patients secondary progressive), who were selected from Tehran Community of MS Patients Supported as convenience sampling. 30 normal persons were also selected as a comparison group. Montreal Cognitive Assessment (MOCA) was used to assess cognitive functions. Data were analyzed using multivariate analysis of variance. Results: The results showed that there were significant differences among cognitive functioning in patients with RRMS, SPMS, and normal individuals. There were not significant differences in working memory between two groups of patients with RRMS and SPMS; while significant differences in these variables were seen between the two groups and normal individuals. Also, results showed significant differences in attention and centralization and visual-spatial perception among three groups. Conclusions: Results showed that there are differences between cognitive functions of RRMS and SPMS patients so that the functions of RRMS patients are better than SPMS patients. These results have a critical role in improvement of cognitive functions; reduce the factors causing disability due to cognitive impairment, and especially overall health of society.

Keywords: multiple sclerosis, cognitive function, secondary-progressive, normal subjects

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Authors: Athicha Cherdpunt, Patompong Satapornpong

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The medical cannabis is made up of components also known as cannabinoids, which consists of two ingredients which are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Interestingly, the Cannabinoid can be used for many treatments such as chemotherapy, including nausea and vomiting, cachexia, anorexia nervosa, spinal cord injury and disease, epilepsy, pain, and many others. However, the adverse drug reactions (ADRs) of THC can cause sedation, anxiety, dizziness, appetite stimulation and impairments in driving and cognitive function. Furthermore, genetic polymorphisms of CYP2C9, CYP2C19 and CYP3A4 influenced the THC metabolism and might be a cause of ADRs. Particularly, CYP2C19*17 allele increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (UM). The aim of this study, is to investigate the frequency of CYP2C19*17 alleles in Thai patients who have been treated with medical cannabis. We prospectively enrolled 60 Thai patients who were treated with medical cannabis and clinical data from College of Pharmacy, Rangsit University. DNA of each patient was isolated from EDTA blood, using the Genomic DNA Mini Kit. CYP2C19*17 genotyping was conducted using the real time-PCR ViiA7 (ABI, Foster City, CA, USA). 30 patients with medical cannabis-induced ADRs group, 20 (67%) were female, and 10 (33%) were male, with an age range of 30-69 years. On the other hand, 30 patients without medical cannabis-induced ADRs (control group) consist of 17 (57%) female and 13 (43%) male. The most ADRs for medical cannabis treatment in the case group were dry mouth and dry throat (77%), tachycardia (70%), nausea (30%) and arrhythmia(10%). Accordingly, the case group carried CYP2C19*1/*1 (normal metabolizer) approximately 93%, while 7% patients carrying CYP2C19*1/*17 (ultra rapid metabolizers) exhibited in this group. Meanwhile, we found 90% of CYP2C19*1/*1 and 10% of CYP2C19*1/*17 in control group. In this study, we identified the frequency of CYP2C19*17 allele in Thai population which will support the pharmacogenetics biomarkers for screening and avoid ADRs of medical cannabis treatment.

Keywords: CYP2C19, allele frequency, ultra rapid metabolizer, medical cannabis

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Authors: Fatimah Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of colon cancer in Saudi patients. Our results were carried out on 48 patients colon cancer. We obtained our data from laboratory in King Khalid university hospital. The specimens were taken (48) patients with colon cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as I in tow patients (male and female) and grade 2 in 42 patients (29 male and 13 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining , immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients of adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscularis layer. With advancing the disease, there were haemorge in blood and increase in lymphocytes and increase number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20,PCNA,P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for pcan and the grades. In our sections, there were strong reactions in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of colon cancer.

Keywords: DNA-CK20, PCNA, P53, colon cancer

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Authors: Fatimah A. Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: cancer, CK20, DNA, cytometry analysis, liver, immunohistochemical, molecular changes, PCNA, p53

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Authors: Eda Jazexhiu-Postoli, Gladiola Hoxha, Ada Simeoni, Sonila Biba

Abstract:

Background Neonatal hypotonia represents a commonly encountered issue in the Neonatal Intensive Care Unit and newborn nursery. The differential diagnosis is broad, encompassing chromosome abnormalities, primary muscular dystrophies, neuropathies and inborn errors of metabolism. Aim of study Our study describes some of the main clinical features of hypotonia in newborns and presents clinical cases of neonatal hypotonia we treated in our Neonatal unit in the last 3 years. Case reports Four neonates born in our hospital presented with hypotonia after birth, one preterm newborn 35-36 weeks of gestational age and three other term newborns (38-39 weeks of gestational age). Prenatal data revealed a decrease in fetal movements in both cases. Intrapartum meconium-stained amniotic fluid was found in 75% of our hypotonic newborns. Clinical features included inability to establish effective respiratory movements and need for resuscitation in the delivery room, respiratory distress syndrome, feeding difficulties and need for oro-gastric tube feeding, dysmorphic features, hoarse voice and moderate to severe muscular hypotonia. The genetic workup revealed the diagnosis of Autosomal Recessive Congenital Myasthenic Syndrome 1-B, Sotos Syndrome, Spinal Muscular Atrophy Type 1 and Transient Hypotonia of the Newborn. Two out of four hypotonic neonates were transferred to the Pediatric Intensive Care Unit and died at the age of three to five months old. Conclusion Hypotonia is a concerning finding in neonatal care and it is suggested by decreased intrauterine fetal movements, failure to establish first breaths, respiratory distress and feeding difficulties in the neonate. Prognosis is determined by its etiology and time of diagnosis and intervention.

Keywords: hypotonic neonate, respiratory distress, feeding difficulties, fetal movements

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Authors: Zeina Merabi, Arij Dao

Abstract:

The temporal order of information processing in the brain is an important code in many acoustic signals, including speech, music, and animal vocalizations. Despite its significance, surprisingly little is known about its underlying cellular mechanisms and network manifestations. In the songbird telencephalic nucleus HVC, a subset of neurons shows temporal combination sensitivity (TCS). These neurons show a high temporal specificity, responding differently to distinct patterns of spectral elements and their combinations. HVC neuron types include basal-ganglia-projecting HVCX, forebrain-projecting HVCRA, and interneurons (HVC¬INT), each exhibiting distinct cellular, electrophysiological and functional properties. In this work, we develop conductance-based neural network models connecting the different classes of HVC neurons via different wiring scenarios, aiming to explore possible neural mechanisms that orchestrate the combination sensitivity property exhibited by HVCX, as well as replicating in vivo firing patterns observed when TCS neurons are presented with various auditory stimuli. The ionic and synaptic currents for each class of neurons that are presented in our networks and are based on pharmacological studies, rendering our networks biologically plausible. We present for the first time several realistic scenarios in which the different types of HVC neurons can interact to produce this behavior. The different networks highlight neural mechanisms that could potentially help to explain some aspects of combination sensitivity, including 1) interplay between inhibitory interneurons’ activity and the post inhibitory firing of the HVCX neurons enabled by T-type Ca2+ and H currents, 2) temporal summation of synaptic inputs at the TCS site of opposing signals that are time-and frequency- dependent, and 3) reciprocal inhibitory and excitatory loops as a potent mechanism to encode information over many milliseconds. The result is a plausible network model characterizing auditory processing in HVC. Our next step is to test the predictions of the model.

Keywords: combination sensitivity, songbirds, neural networks, spatiotemporal integration

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Authors: Maftunakhon Latipova, Feruza Khaydarova

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Obesity is considered a chronic metabolic disease that occurs at any age. Regulation of body weight in the body is carried out through complex interaction of a complex of interrelated systems that control the body's energy system. Energy imbalance is the cause of obesity and overweight, in which the supply of energy from food exceeds the energy needs of the body. Obesity is closely related to impaired appetite regulation, and a hypothalamus is a key place for neural regulation of food consumption. The nucleus of the hypothalamus is connected and interdependent on receiving, integrating and sending hunger signals to regulate appetite. Purpose of the study: to identify markers of food behavior. Materials and methods: The screening was carried out to identify eating disorders in 200 men and women aged 18 to 35 years with overweight and obesity and to check the effects of Orexin A and Neuropeptide Y markers. A questionnaire and questionnaires were conducted with over 200 people aged 18 to 35 years. Questionnaires were for eating disorders and hidden depression (on the Zang scale). Anthropometry is measured by OT, OB, BMI, Weight, and Height. Based on the results of the collected data, 3 groups were divided: People with obesity, People with overweight, Control Group of Healthy People. Results: Of the 200 analysed persons, 86% had eating disorders. Of these, 60% of eating disorders were associated with childhood. According to the Zang test result: Normal condition was about 37%, mild depressive disorder 20%, moderate depressive disorder 25% and 18% of people suffered from severe depressive disorder without knowing it. One group of people with obesity had eating disorders and moderate and severe depressive disorder, and group 2 was overweight with mild depressive disorder. According to laboratory data, the first group had the lowest concentration of Orexin A and Neuropeptide U in blood serum. Conclusions: Being overweight and obese are the first signal of many diseases, and prevention and detection of these disorders will prevent various diseases, including type 2 diabetes. Obesity etiology is associated with eating disorders and signal transmission of the orexinorghetic system of the hypothalamus.

Keywords: obesity, endocrinology, hypothalamus, overweight

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Authors: Eitan Yefenof

Abstract:

Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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