Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence.

Anticancer chemotherapy (ACT) remains a cornerstone in cancer treatment, despite significant advances in pharmacology over recent decades. However, its associated side effect toxicity continues to pose a major concern for both oncology clinicians and patients, significantly impacting treatment protocols and patient quality of life. Current clinical strategies to mitigate ACT-induced toxicity have proven largely unsatisfactory, leaving a critical unmet need to block toxicity mechanisms without diminishing ACT's therapeutic efficacy. This review aims to document the molecular mechanisms underlying ACT toxicity and highlight research efforts exploring the protective effects of trace elements (TEs) and their nanoparticles (NPs) against these mechanisms. Our literature review reveals that the primary driver of ACT toxicity is redox imbalance, which triggers oxidative inflammation, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, autophagy, and dysregulation of signaling pathways such as PI3K/mTOR/Akt. Studies suggest that TEs, including zinc, selenium, boron, manganese, and molybdenum, and their NPs, can potentially counteract ACT-induced toxicity by inhibiting oxidative stress-mediated pathways, including NF-κB/TLR4/MAPK/NLRP3, STAT-3/NLRP3, Bcl-2/Bid/p53/caspases, and LC3/Beclin-1/CHOP/ATG6, while also upregulating protective signaling pathways like Sirt1/PPAR-γ/PGC-1α/FOXO-3 and Nrf2/HO-1/ARE. However, evidence regarding the roles of lncRNA and the Wnt/ß-catenin pathway in ACT toxicity remains inconsistent, and the impact of TEs and NPs on ACT efficacy is not fully understood. Further research is needed to confirm the protective effects of TEs and their NPs against ACT toxicity in cancer patients. In summary, TEs and their NPs present a promising avenue as adjuvant agents for preventing non-target organ toxicity induced by ACT.

Fibrinogen as a Predictor of Early Neurological Deterioration and Poor Outcome in Acute Ischemic Stroke.

There has been more than a 100 per cent increase in stroke incidence in India from 1970 - 2008. Early Neurological Deterioration (END) is associated with an increased risk of disability and mortality in ischemic stroke patients and approximately 32% of ischemic stroke patients experience END. Although various factors have been identified to predict the occurrence of END in ischemic stroke such as age, gender, diabetes, initial stroke severity, stroke subtype and radiological parameters, similar data for the Indian population is lacking. Fibrinogen is a mediator in the development of coronary artery thrombi and future cardiac events and has been reported to be independently associated with a poor functional outcome. MATERIAL: We enrolled 141 patients with acute ischemic stroke from a single centre. END was defined as a total National Institutes of Health Stroke Scale (NIHSS) score deterioration by 2 or more points within the first week. Patients with a Modified Rankin Scale (MRS) score of 3 or more at discharge, or a stroke recurrence event during hospital stay were said to have a poor outcome. We performed univariate analysis in the total population to develop a logistic regression model to assess potential factors associated with END and poor outcome. OBSERVATION: Fibrinogen levels were higher in the END group than the non - END group (464.57 ± 121.05 vs. 305.0 ± 123.28, p <0.001) and was an independent predictor for END in the logistic regression model (odds ratio 1.011, p <0.001). Increasing age and a higher NIHSS score at admission were other risk factors for developing END. Fibrinogen was also independently associated with poor outcome (odds ratio 1.004, p = 0.038) along with initial NIHSS score and fasting blood sugar level. CONCLUSION: Fibrinogen levels at stroke onset is independently associated with END and a worse hospital outcome in an Indian population subset with ischemic stroke. Routine plasma fibrinogen assays may help clinicians in stratifying patients into a high-risk group, who may require more potent antiplatelet therapy or use of fibrin-depleting agents.

Permanent isolated micrographia from traumatic basal ganglia injury.

Micrographia is a rare neurological finding in isolation. Most cases of isolated micrographia have been found in association with focal ischemia of the left basal ganglia. Here, we present a case of post-traumatic micrographia stemming from contusion to the left basal ganglia.

Ultrafast Self-Induced X-Ray Transparency and Loss of Magnetic Diffraction.

Using ultrafast ≃2.5 fs and ≃25 fs self-amplified spontaneous emission pulses of increasing intensity and a novel experimental scheme, we report the concurrent increase of stimulated emission in the forward direction and loss of out-of-beam diffraction contrast for a Co/Pd multilayer sample. The experimental results are quantitatively accounted for by a statistical description of the pulses in conjunction with the optical Bloch equations. The dependence of the stimulated sample response on the incident intensity, coherence time, and energy jitter of the employed pulses reveals the importance of increased control of x-ray free electron laser radiation.

Unusual array of neural communications in the infratemporal fossa: Useful for skull base surgery.

Variations in the branching pattern of the mandibular nerve frequently accounts for failure to obtain adequate local anesthesia in routine oral and dental procedures, and also for unexpected injury to the nerves during surgery. The knowledge of the neurovascular relationships of the infratemporal region is relevant in odontostomatology practice. In this article we present a rare case of atypical communication between the inferior alveolar nerve and lingual nerve and the mylohyoid and lingual nerves. Further, the clinical implications of these communications on the development of the supplementary innervation and their possible role in anesthesia is discussed in detail. The communication between mylohyoid and lingual nerve was found in this case near the submandibular ganglion after the lingual nerve passes in close relation to third molar tooth, which makes it more susceptible to injury during third molar extractions. The communicating branch between the mylohyoid nerve and lingual nerve may also innervate the tongue, and surgeons should be aware of this variation to avoid post- operative complcations after oral surgeries. Thus the precise anatomy of structures of infratemporal region and its variations may prove beneficial to clinicians, especially to oral and maxillofacial surgeons.

Bilateral clavicular attachment of omohyoid muscle.

Omohyoid muscle present in cervical region is of particular importance to anatomists as it defines anteriorly the carotid triangle and divides the posterior cervical triangle. It has superior and inferior bellies and an intermediate common tendon. Like sternohyoid, sternothyroid and thyrohyoid muscles, omohyoid is also an infrahyoid muscle, but it differs from them in its course. The infrahyoid muscles are formed from a muscle primordium occurring in the anterior cervical area. Anderson (Anderson, 1881) theorized that the superior belly of the omohyoid muscle is a true infrahyoid muscle, whereas the inferior belly most likely shares a common embryology with the subclavius muscle. In the present study, during routine dissection in the neck region of an adult male cadaver of 50 years age, an anomalous origin of inferior belly of omohyoid with absence of intermediate tendon was observed bilaterally. It was arising from clavicle on both sides. Both the muscle bellies were measured from the lateral end of fascial sling. The inferior belly of omohyoid extending from the lateral margin of sling to clavicular surface was measured 3.3cm in length on left side and 3.6cm on right side. The omohyoid is important in neck dissections because it is considered as an ideal landmark for level III and IV lymph node metastases. Knowledge of variations of this muscle is very important for surgeries in neck region because of its close relation to the internal jugular vein and brachial plexus. Its crucial relationship to vascular structures in the neck makes it an important landmark during neck surgeries.

Characterization of peripheral and central sensitization after dorsal root ganglion intervention in patients with unilateral lumbosacral radicular pain: a prospective pilot study.

BACKGROUND.: Quantitative sensory testing (QST) has been used to predict the outcome of epidural steroid injections in lumbosacral radicular pain and has the potential to be an important tool in the selection of appropriate treatment (such as epidural steroid injections vs surgery) for patients with chronic radicular pain. In addition, QST assists in identification of the pain pathways of peripheral and central sensitization in selected groups of patients. METHODS.: Twenty-three patients were given dorsal root ganglion (DRG) infiltration with local anaesthesia and steroid ('DRG block'), and those who demonstrated at least 50% pain relief were offered pulsed radiofrequency (PRF) to the DRG. Questionnaires and QST scores were measured before the DRG blocks and at 1 week and 3 months after their procedure. Those who received PRF also answered questionnaires and underwent QST measurements at 1 week and 3 months after their procedure. RESULTS.: There was a significant increase in pressure pain threshold scores after DRG blocks. A reduced conditioned pain modulation response was seen before DRG, which increased after the procedure. Ten out of 23 patients underwent PRF to the DRG, and an increase in pressure pain threshold scores after PRF was observed. The conditioned pain modulation response was maintained in this group and increased after PRF. CONCLUSIONS.: The study demonstrates that patients with unilateral radicular low back pain who receive dorsal root ganglion interventions show changes in pressure pain thresholds and conditioned pain modulation that are consistent with a 'normalization' of peripheral and central sensitization.

Study of interleukin-6 and interleukin-8 levels in patients with neurological manifestations of dengue.

CONTEXT: Pro-inflammatory markers play a key role in the pathogenesis of various Flavivirus infection. AIM: In this study, we evaluated the role of these markers in neurological manifestations of dengue. SETTINGS AND DESIGNS: Consecutive dengue cases with different neurological manifestations who presented between August 2012 and July 2014 were studied in hospital-based case-control study. MATERIALS AND METHODS: Interleukin (IL-6) and IL-8 level were measured in serum and cerebrospinal fluid (CSF) of dengue cases with different neurological manifestations and also in age- and sex-matched controls. Level was analyzed with various parameters and outcomes. STATISTICAL ANALYSIS: Statistical analysis was done using SPSS version 16.0 by applying appropriate statistical methods. P < 0.05 considered statistically significant. RESULTS: Out of the 40 enrolled cases of dengue with neurological manifestations, 29 had central nervous system and 11 had peripheral nervous system (CNS/PNS) manifestations. In CNS group, both IL-6 and IL-8 (CSF and serum) were significantly elevated (P < 0.001), whereas CSF IL-6 (P = 0.008), serum IL-6 (P = 0.001), and serum IL-8 (P = 0.005) were significantly elevated in PNS group. CSF IL-6, serum IL-6, and IL-8 were significantly elevated in poor outcome patients in CNS group (P < 0.05). CSF IL-6 and IL-8 were significantly elevated in CSF dengue positive cases as compared to CSF negative patients (P < 0.05). Cytokine level was not significantly correlated with neuroimaging abnormality in CNS group. Nine patients died and the remainder recovered. CONCLUSION: Elevated level of IL-6 and IL-8 is associated with different neurological manifestations and poor outcome, but whether they are contributing to neuropathogenesis or simply a correlate of severe disease remains to be determined.

Variant lumbrical musculature of the left hand: Clinico-anatomic elucidation.

Human hand is haughtily described in literature as 'revolution in evolution'. Lumbricals form an intricate part of its musculature playing a vital role in complex digital movements. By virtue of their origin from the volar aspect of palm and their insertion onto the dorsal aspect to the extensor digital expansion of the digits, lumbricals display complex actions flexing the metacarpophalangeal joint and extending the interphalangeal joints. Such manoeuvres of the digits are vital for skilful and precision movements. During routine dissection of the teaching program of undergraduate medical students, unusual origin and morphology of all the four lumbrical muscles in the left hand of a male cadaver was observed. Clinicians and hand surgeons should be aware of its variations while designing and dealing with hand surgeries. An attempt has been made to comprehend its clinical, embryological and phylogenetic aspects.

Interfacial ferromagnetism in LaNiO3/CaMnO3 superlattices.

We observe interfacial ferromagnetism in superlattices of the paramagnetic metal LaNiO3 and the antiferromagnetic insulator CaMnO3. LaNiO3 exhibits a thickness dependent metal-insulator transition and we find the emergence of ferromagnetism to be coincident with the conducting state of LaNiO3. That is, only superlattices in which the LaNiO3 layers are metallic exhibit ferromagnetism. Using several magnetic probes, we have determined that the ferromagnetism arises in a single unit cell of CaMnO3 at the interface. Together these results suggest that ferromagnetism can be attributed to a double exchange interaction among Mn ions mediated by the adjacent itinerant metal.

Stem cell therapy for stress urinary incontinence: a systematic review in human subjects.

PURPOSE: To systematically evaluate the current evidence on the safety and efficacy of stem cell therapy (SCT) in stress urinary incontinence (SUI) to allow objective comparison with existing surgical techniques. METHODS: Systematic literature search of Medline from years 1946-2012 using terms: "stem", "cell", "stress", "urinary", and "incontinence". Included studies presented empirical data on the treatment of SUI using SCT. OUTCOMES: adverse events, incontinence, quality of life, urodynamic, transurethral ultrasound and urethral EMG findings. RESULTS: Eight studies met inclusion criteria (seven observational and one randomized). Quality score: median 10.75 of 20 (range 2-12.5). Adverse events: one patient had bladder perforation and two procedures could not be completed due to pain. Temporary urinary retention and cystitis were also reported. Incontinence score: Four studies describe significant improvement. Quality of life: significant improvement in four studies. Urodynamic outcomes: four studies show significant improvement in contractility of urethral sphincter; three studies demonstrate no change in bladder capacity and significant reduction in residual volume; significant improvement in urinary flow three studies, although two found no difference; increase in leak point pressure and detrusor pressure in three studies. Urethral ultrasound: three studies found significant increases in rhabdosphincter thickness and contractility. Urethral EMG: two studies found significant increases in the EMG at rest and at contraction. CONCLUSION: Data suggest that SC treatment for SUI is safe and effective in the short term. However, the quality and maturity of the data are limited. Robust data from better quality studies comparing this to current surgical techniques are needed.

Spinal dural arterio-venous fistula: clinico-radiological profile and outcome following surgical occlusion in an Indian neurosurgical center.

BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) is a common type of spinal vascular lesion. However, there has not been any published study on its clinico-radiological characteristics or surgical outcome from India. AIM: The aim of this study was to determine the clinico-radiological features of patients with SDAVF, outcomes following surgical ligation of the fistula and the various factors involved. MATERIALS AND METHODS: Patients who were operated for SDAVF were studied for demographic details, symptoms, clinical severity, radiological features and neurological outcome in the form of improvement in gait disability grades. Appropriate statistical tests were performed. RESULTS: There were 22 (19 males, 3 females) patients of SDAVF who underwent surgical ligation with a mean age of 55 years. The mean duration of symptoms at presentation was 15 months. Three patients had acute onset while the rest had insidious onset of symptoms. Out of the 22 patients, 11 (50%) had motor weakness as the first symptom, 13 (59%) were bedridden and 19 (86.4%) had bladder involvement at presentation. Thirteen patients had fistulae in thoracic spine, whereas eight had fistulae in the lumbar spine. All had a favorable outcome in the form of at least non-progression of gait disability (14 had improvement while 8 had stabilized). The improvement was non-significantly associated with younger age, acute onset, ambulant status and fistula below T9. It was inversely associated with pain as the first symptom and fluctuant clinical course. CONCLUSION: Surgical occlusion of SDAVF is usually associated with either improvement or stabilization of motor weakness.

Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A(165) in the uterine arteries of pregnant sheep.

Increasing uterine artery blood flow (UABF) may benefit fetal growth restriction where impaired uteroplacental perfusion prevails. Based on previous short-term results, we examined the long-term effects of adenovirus vector-mediated overexpression of vascular endothelial growth factor-A(165) (VEGF-A(165)) in the uterine artery (UtA). Transit-time flow probes were implanted around both UtAs of mid-gestation pregnant sheep (n=11) to measure UABF. A carotid artery catheter was inserted to measure maternal or fetal hemodynamics. Baseline UABF was measured over 3 days, before injection of adenovirus vector (5 × 10(11) particles) encoding the VEGF-A(165) gene (Ad.VEGF-A(165)) into one UtA and a reporter ß-galactosidase gene (Ad.LacZ) contralaterally. UABF was then measured daily until term. At 4 weeks post injection, the increase in UABF was significantly higher in Ad.VEGF-A(165) compared with Ad.LacZ-transduced UtAs (36.53% vs 20.08%, P=0.02). There was no significant effect on maternal and fetal blood pressure. Organ bath studies showed significantly lesser vasoconstriction (E(max) 154.1 vs 184.7, P<0.001), whereas immunohistochemistry demonstrated a significantly increased number of adventitial blood vessels (140 vs 91, n=26, P<0.05) following Ad.VEGF-A(165) transduction. Local overexpression of VEGF-A(165) in the UtAs of pregnant mid-gestation sheep leads to a sustained long-term increase in UABF, which may be explained by neovascularization and altered vascular reactivity.

Interfacial ferromagnetism and exchange bias in CaRuO3/CaMnO3 superlattices.

We have found ferromagnetism in epitaxially grown superlattices of CaRuO(3)/CaMnO(3) that arises in one unit cell at the interface. Scanning transmission electron microscopy and electron energy loss spectroscopy indicate that the difference in magnitude of the Mn valence states between the center of the CaMnO(3) layer and the interface region is consistent with double exchange interaction among the Mn ions at the interface. Polarized neutron reflectivity and the CaMnO(3) thickness dependence of the exchange bias field together indicate that the interfacial ferromagnetism is only limited to one unit cell of CaMnO(3) at each interface. The interfacial moment alternates between the 1 µ(B)/interface Mn ion for even CaMnO(3) layers and the 0.5 µ(B)/interface Mn ion for odd CaMnO(3) layers. This modulation, combined with the exchange bias, suggests the presence of a modulating interlayer coupling between neighboring ferromagnetic interfaces via the antiferromagnetic CaMnO(3) layers.

Clinico-embryological submission of an unilateral anomalous presentation of axillary artery.

OBJECTIVES: Descriptions of the variant arterial pattern of upper limb are not exceptional and are therefore frequently reported in anatomy archives. BACKGROUND: A noteworthy deviation from the usual branching pattern was observed unilaterally in a single cadaver. This unique division of axillary artery (AA) was present on the right side in an adult human cadaver of Indian origin. RESULTS: The first part of axillary artery gave off the superior thoracic and thoraco-acromial arteries. Just proximal to the upper border of pectoralis minor the AA was observed to divide into two trunks a medial and a lateral. The lateral trunk continued into the brachium as the usual axillary artery where as the medial trunk displayed the other branches deep and distal to the pectoralis minor muscle. The remarkable feature was the wide caliber of the axillary artery where it bifurcated into two branches. An attempt has been made to dwell upon the embryological basis of the present anomaly. CONCLUSIONS: The relevance of anomalous arterial pattern of upper limb (U.L.) is realized while performing percutaneous arterial venous catheter insertion into subclavian vein via the infraclavicular route. We advocate a meticulous familiarization of the anatomy of axillary artery and its topographical relationship to other neurovascular structures for the operating plastic surgeon, anesthetist and radiologist (Fig. 1, Ref. 12).

Repeat resection in recurrent glioblastoma (3rGBM) Trial: A randomized care trial.

BACKGROUND: The prognosis for patients with recurrent glioblastoma (GBM) is dismal, and the question of repeat surgery at time of recurrence is common. Re-operation in the management of these patients remains controversial, as there is no randomized evidence of benefit. An all-inclusive pragmatic care trial is needed to evaluate the role of repeat resection. METHODS: 3rGBM is a multicenter, pragmatic, prospective, parallel-group randomized care trial, with 1:1 allocation to repeat resection or standard care with no repeat resection. To test the hypothesis that repeat resection can improve overall survival by at least 3 months (from 6 to 9 months), 250 adult patients with prior resection of pathology-proven glioblastoma for whom the attending surgeon believes repeat resection may improve quality survival will be enrolled. A surrogate measure of quality of life, the number of days outside of hospital/nursing/palliative care facility, will also be compared. Centers are invited to participate without financial compensation and without contracts. Clinicians may apply to local authorities to approve an investigator-led in-house trial, using a common protocol, web-based randomization platform, and simple standardized case report forms. DISCUSSION: The 3rGBM trial is a modern transparent care research framework with no additional risks, tests, or visits other than what patients would encounter in normal care. The burden of proof remains on repeat surgical management of recurrent GBM, because this management has yet to be shown beneficial. The trial is designed to help patients and surgeons manage the uncertainty regarding optimal care. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov. Unique identifier: NCT04838782.

A cross-sectional evaluation of computer literacy among medical students at a tertiary care teaching hospital in Mumbai, Bombay.

BACKGROUND: Computer usage capabilities of medical students for introduction of computer-aided learning have not been adequately assessed. AIM: Cross-sectional study to evaluate computer literacy among medical students. SETTINGS AND DESIGN: Tertiary care teaching hospital in Mumbai, India. MATERIALS AND METHODS: Participants were administered a 52-question questionnaire, designed to study their background, computer resources, computer usage, activities enhancing computer skills, and attitudes toward computer-aided learning (CAL). The data was classified on the basis of sex, native place, and year of medical school, and the computer resources were compared. The computer usage and attitudes toward computer-based learning were assessed on a five-point Likert scale, to calculate Computer usage score (CUS - maximum 55, minimum 11) and Attitude score (AS - maximum 60, minimum 12). The quartile distribution among the groups with respect to the CUS and AS was compared by chi-squared tests. The correlation between CUS and AS was then tested. RESULTS: Eight hundred and seventy-five students agreed to participate in the study and 832 completed the questionnaire. One hundred and twenty eight questionnaires were excluded and 704 were analyzed. Outstation students had significantly lesser computer resources as compared to local students (P<0.0001). The mean CUS for local students (27.0±9.2, Mean±SD) was significantly higher than outstation students (23.2±9.05). No such difference was observed for the AS. The means of CUS and AS did not differ between males and females. The CUS and AS had positive, but weak correlations for all subgroups. CONCLUSION: The weak correlation between AS and CUS for all students could be explained by the lack of computer resources or inadequate training to use computers for learning. Providing additional resources would benefit the subset of outstation students with lesser computer resources. This weak correlation between the attitudes and practices of all students needs to be investigated. We believe that this gap can be bridged with a structured computer learning program.

Accessory muscle belly of peroneus tertius in the leg--a rare anatomical variation with clinical relevance--utility in reconstructions.

We report here a rare muscular anomaly of the lower leg in an adult male cadaver observed during routine cadaveric dissection. Peroneus tertius (PT) is peculiar to man, being a hallmark of bipedal locomotion and erect posture. During the course of gross anatomy dissection, a rare finding of accessory belly of PT muscle was discovered. A meticulous dissection was performed and the observations were noted. The PT displayed two distinct bellies of origin. Both the bellies were substantial in size and were eventually fused close to their insertion at the base of the fifth meta-tarsal bone. Innervation of both the bellies was derived from the deep peroneal nerve. Soft tissue defects of the leg may be effectively covered by local muscles in the vicinity of the wounds. PT has been reliably used in the past for local transposition flaps in the lower extremities. The relations of the superficial nerve and the PT during placement of the anterolateral portal in ankle arthroscopy are vital to avoid inadvertent neuromuscular injuries. The presence of two bellies of the PT muscle has been discussed in the comparative perspective. A precise and detailed knowledge of the anatomical details of the crural muscles is important for performing reconstructive surgeries.

Complex roles of discoidin domain receptor tyrosine kinases in cancer.

Discoidin domain receptors, DDR1 and DDR2 are members of the receptor tyrosine kinase (RTK) family that serves as a non-integrin collagen receptor and were initially identified as critical regulators of embryonic development and cellular homeostasis. In recent years, numerous studies have focused on the role of these receptors in disease development, in particular, cancer where they have been reported to augment ECM remodeling, invasion, drug resistance to facilitate tumor progression and metastasis. Interestingly, accumulating evidence also suggests that DDRs promote apoptosis and suppress tumor progression in various human cancers due to which their functions in cancer remain ill-defined and presents a case of an interesting therapeutic target. The present review has discussed the role of DDRs in tumorigenesis and the metastasis.