Developmental coordination disorder: What can we learn from RI mice using motor learning tasks and QTL analysis.

Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder of unknown etiology that affects one in 20 children. There is an indication that DCD has an underlying genetic component due to its high heritability. Therefore, we explored the use of a recombinant inbred family of mice known as the BXD panel to understand the genetic basis of complex traits (i.e., motor learning) through identification of quantitative trait loci (QTLs). The overall aim of this study was to utilize the QTL approach to evaluate the genome-to-phenome correlation in BXD strains of mice in order to better understand the human presentation of DCD. Results of this current study confirm differences in motor learning in selected BXD strains and strains with altered cerebellar volume. Five strains - BXD15, BXD27, BXD28, BXD75, and BXD86 - exhibited the most DCD-like phenotype when compared with other BXD strains of interest. Results indicate that BXD15 and BXD75 struggled primarily with gross motor skills, BXD28 primarily had difficulties with fine motor skills, and BXD27 and BXD86 strains struggled with both fine and gross motor skills. The functional roles of genes within significant QTLs were assessed in relation to DCD-like behavior. Only Rab3a (Ras-related protein Rab-3A) emerged as a high likelihood candidate gene for the horizontal ladder rung task. This gene is associated with brain and skeletal muscle development, but lacked nonsynonymous polymorphisms. This study along with Gill et al. (same issue) is the first studies to specifically examine the genetic linkage of DCD using BXD strains of mice.

A scoping review of military and Veteran families within international suicidality and suicide prevention research.

The impacts of suicidality on families are well known, which is particularly relevant in at-risk populations, such as active duty military personnel and Veteran communities. This scoping review describes how military and Veteran families have been conceptualized within suicide prevention research. A systematic, multi-database search was conducted, and 4,835 studies were screened. All included studies underwent quality assessment. Bibliographic, participant, methodological, and family-relevant data was extracted and descriptively analyzed into Factors, Actors, and Impacts. In total, 51 studies (2007 - 2021) were included. Most studies focused on suicidality rather than suicide prevention. Factor studies described family constructs as a suicidality risk or protective factor for military personnel or Veterans. Actor studies described families' roles or responsibilities to act in relation to the suicidality of military personnel or Veterans. Impacts studies described the impacts of suicidality on military and Veteran family members. The search was limited to English language studies. There were few studies on suicide prevention interventions for or including military and Veteran family members. Family was typically considered peripheral to the military personnel or Veteran experiencing suicidality. However, there was also emerging evidence of suicidality and its consequences in military-connected family members.

Cerebellar and brainstem differences in children with developmental coordination disorder: A voxel-based morphometry study.

Developmental coordination disorder (DCD) is a neurodevelopmental disorder that significantly impairs a child's ability to learn motor skills and to perform everyday activities. The cause of DCD is unknown; however, evidence suggests that children with DCD have altered brain structure and function. While the cerebellum has been hypothesised to be involved in developmental coordination disorder, no studies have specifically examined cerebellar structure in this population. The purpose of our study was to examine cerebellar differences in children with DCD compared to typically-developing children. Using voxel-based morphometry, we assessed cerebellar morphology in children 8-12 years of age. Forty-six children (12 typically-developing and 34 with DCD) were investigated using high resolution T1-weighted images, which were then processed using the spatially unbiased atlas template of the cerebellum and brainstem (SUIT) toolbox for a region of interest-based examination of the cerebellum. Results revealed that children with DCD had reduced grey matter volume in several regions, namely: the brainstem, right/left crus I, right crus II, left VI, right VIIb, and right VIIIa lobules. Further, Pearson correlations revealed significant positive associations between the total motor percentile score on the Movement Assessment Battery for Children-2 and regions that had reduced grey matter volume in our cohort (brainstem, left crus I, right VIIb, and right VIIIa). These findings indicate that reductions in cerebellar grey matter volume are associated with poorer motor skills. Given the cerebellum's involvement in internal models of movement, results of this study may help to explain why children with DCD struggle to learn motor skills.

Cerebellar Differences after Rehabilitation in Children with Developmental Coordination Disorder.

Developmental coordination disorder (DCD) affects a child's ability to learn motor skills. Cognitive Orientation to daily Occupational Performance (CO-OP) is one of the recommended treatments to help achieve functional motor goals. The purpose of this study was to determine if CO-OP intervention induces functional improvements and structural changes in the cerebellum of children with DCD. Using a randomized waitlist-controlled trial, we investigated the effects of CO-OP intervention on cerebellar volume in 47 children with DCD (8-12 years old). Outcome measures included the Canadian Occupational Performance Measure, Performance Quality Rating Scale (PQRS), and Bruininks-Oseretsky Test of Motor Proficiency-2. The SUIT toolbox was used to carry out voxel-based morphometry using T1-weighted MRI scans. Children with DCD showed improved motor outcomes and increased gray matter volume in the brainstem, right crus II, bilateral lobules VIIIb, and left lobule IX following CO-OP. Significant associations were found between PQRS scores and regional gray matter changes in the brainstem, right crus II, right lobule VIIb, right and left lobule VIIIb, and vermis IX. Given the improved motor and brain outcomes with CO-OP, it is recommended that children with DCD be referred for this rehabilitation intervention.

Using a mouse model to gain insights into developmental coordination disorder.

Motor impairments are a common feature of many neurodevelopmental disorders; in fact, over 50% of children with Attentional Deficit Hyperactivity Disorder or Autism Spectrum Disorder may have a co-occurring diagnosis of developmental coordination disorder (DCD). DCD is a neurodevelopmental disorder of unknown etiology that affects motor coordination and learning, significantly impacting a child's ability to carry out everyday activities. Animal models play an important role in scientific investigation of behaviour and the mechanisms and processes that are involved in control of motor actions. The purpose of this paper is to present an approach in the mouse directed to gain behavioral and genetic insights into DCD that is designed with high face validity, construct validity and predictive validity. Pre-clinical and clinical expertise is used to establish a set of scientific criteria that the model will meet in order to investigate the potential underlying causes of DCD.

Deferred diagnosis in children assessed for fetal alcohol spectrum disorder.

Early intervention for individuals with FASD is paramount, thus exploring factors that affect the diagnostic process is critical. This process can be complicated by challenges gathering background information, accurately evaluating higher-level cognitive skills across ages, and teasing apart the impact of life adversities from the effects of prenatal alcohol exposure. This study is a retrospective file review of 154 children (44% female; mean age 8.4 years, range 1.0 to 16.9) deferred at their first FASD assessment, and 51 (43% female; mean 9.9 years, range 2.7 to 17.2) who returned for a second assessment. Data was collected from three Canadian FASD clinics to explore reasons for deferral, the clinical profile of deferred children, why some returning children were diagnosed while others were not, and changes between assessments. Results suggest that deferred children initially lacked evidence of abnormalities sufficient for a diagnosis, presented with areas of relative neurobehavioral strength and difficulty, and children eventually diagnosed with FASD showed significantly more impaired brain function (p < 0.001, ηp2 = 0.547), postnatal risk (p = 0.021, ηp2 = 0.121), and comorbidities (p = 0.038, ηp2 = 0.085) than undiagnosed children. These findings provide important insights into the process of clinical assessment for FASD.

Health-related quality of life of children with Developmental Coordination Disorder.

BACKGROUND: Although Developmental Coordination Disorder (DCD) is primarily a motor disorder, it can also impact emotional and psychosocial functioning of children with this condition. Evidence suggests that children with DCD experience lower quality of life than their peers, but few studies have explicitly examined the health-related quality of life (HRQOL) of these children. AIMS: To: (1) describe HRQOL of children with DCD compared to typically-developing children; (2) compare HRQOL from the perspectives of children with DCD and their parents; and (3) explore predictors of HRQOL for children with DCD. METHODS: Data from the KidScreen-52 and Strength and Difficulties Questionnaire were collected from 50 children with DCD [Mean(SD) age: 9.8 (1.2) years] and their parents and compared to normative data. RESULTS: Children with DCD and their parents report significantly lower HRQOL compared to published norms. Caregivers have a significantly lower perception of their child's HRQOL than their child's self-report in many domains. Parents of children with DCD report that their children experience significantly more emotional and behavioral disturbances compared to norms. Poor motor function and attentional difficulties predict HRQOL. CONCLUSION AND IMPLICATIONS: DCD appears to contribute to lower perceived HRQOL. Findings inform therapeutic targets for children with DCD, beyond motor skill intervention.

Participation of children with developmental coordination disorder.

Children with developmental coordination disorder (DCD) participate less frequently and in less diverse activities compared to typically-developing children. Participation restrictions have been attributed to poor motor skills, but no studies have examined the influence of the environment on participation of children with DCD. This study examined participation in children with DCD at home, school and in the community, considering both personal and environmental factors. Eighty-one parents of 4- to 12-year-old children with DCD (M = 8.3, SD = 2.1) completed the Participation and Environment Measure-Child and Youth (PEM-CY). Our data were compared to previously published data on typically-developing children. Children with DCD participated less frequently than typically-developing children in school and community settings and had less overall environmental support in all three settings. Regarding improvement in participation, children with DCD would benefit from motor interventions that also focus on modification of the environment to support their participation in home, school, and community settings.

Concurrent Validity of the Bayley-III and the Peabody Developmental Motor Scales-2 at 18 Months.

Aim: To determine concurrent validity between the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III) and the Peabody Developmental Motor Scales, 2nd edition (PDMS-2). Methods: Both assessments were administered to 184 preterm children at 18 months corrected age; standard scores for total score, gross motor, and fine motor were calculated for each child. Cross-tabulation and Pearson correlation coefficient (r) determined concurrent validity between the Bayley-III and the PDMS-2 motor domains. Results: High correlations were found between total motor (r = 0.88), gross motor (r = 0.88), and fine motor scores (r = 0.79). Both assessments had 93% agreement on classification for motor impairment; 23 children were identified by both assessments as having motor impairments, but 12 children were identified differently on each assessment (7 as impaired on PDMS-2 but average on Bayley-III; 5 as impaired on Bayley-III but average on PDMS-2). Most children with motor impairments were identified as 1SD below the mean on the PDMS-2 (27/30) and Bayley-III (18/28); however, the Bayley-III identified more children 2SD below the mean (10/28) compared to the PDMS-2 (3/30). Conclusions: Both the Bayley-III and PDMS-2 identify motor delays in children; however, clinicians should be aware of the concurrent validity as each assessment may lead to differing results.

Epidermal growth factor receptors containing a single tyrosine in their C-terminal tail bind different effector molecules and are signaling-competent.

The EGF receptor is a classic receptor tyrosine kinase. It contains nine tyrosines in its C-terminal tail, many of which are phosphorylated and bind proteins containing SH2 or phosphotyrosine-binding (PTB) domains. To determine how many and which tyrosines are required to enable EGF receptor-mediated signaling, we generated a series of EGF receptors that contained only one tyrosine in their C-terminal tail. Assays of the signaling capabilities of these single-Tyr EGF receptors indicated that they can activate a range of downstream signaling pathways, including MAP kinase and Akt. The ability of the single-Tyr receptors to signal correlated with their ability to bind Gab1 (Grb2-associated binding protein 1). However, Tyr-992 appeared to be almost uniquely required to observe activation of phospholipase Cγ. These results demonstrate that multiply phosphorylated receptors are not required to support most EGF-stimulated signaling but identify Tyr-992 and its binding partners as a unique node within the network. We also studied the binding of the isolated SH2 domain of Grb2 (growth factor receptor-bound protein 2) and the isolated PTB domain of Shc (SHC adaptor protein) to the EGF receptor. Although these adapter proteins bound readily to wild-type EGF receptor, they bound poorly to the single-Tyr EGF receptors, even those that bound full-length Grb2 and Shc well. This suggests that in addition to pTyr-directed associations, secondary interactions between the tail and regions of the adapter proteins outside of the SH2/PTB domains are important for stabilizing the binding of Grb2 and Shc to the single-Tyr EGF receptors.

The rational design of specific peptide inhibitor against p38α MAPK at allosteric-site: a therapeutic modality for HNSCC.

p38α is a significant target for drug designing against cancer. The overproduction of p38α MAPK promotes tumorigenesis in head and neck squamous cell carcinoma (HNSCC). The ATP binding and an allosteric site referred as DFG are the key sites of the p38α mitogen activated protein kinase (MAPK) exploited for the design of inhibitors. This study demonstrated design of peptide inhibitor on the basis of allosteric site using Glide molecular docking software and the biochemical analysis of the best modeled peptide. The best fitted tetrapeptide (FWCS) in the allosteric site inhibited the pure recombinant and serum p38α of HNSCC patients by 74 and 72%, respectively. The potency of the peptide was demonstrated by its IC50 (4.6 nM) and KD (3.41×10-10 M) values, determined by ELISA and by surface plasmon resonance (SPR) technology, respectively. The cell viability of oral cancer i.e. KB cell line was reduced in dose dependent manner by 60 and 97% by the treatment of peptide and the IC50 was 600 and 210 µM after 24 and 72 h incubation, respectively. Our result provides an insight for the development of a proficient small peptide as a promising anticancer agent targeting DFG site of p38α kinase.

Antifungal and antiproliferative protein from Cicer arietinum: a bioactive compound against emerging pathogens.

The emergence of epidemic fungal pathogenic resistance to current antifungal drugs has increased the interest in developing alternative antibiotics from natural sources. Cicer arietinum is well known for its medicinal properties. The aim of this work was to isolate antimicrobial proteins from Cicer arietinum. An antifungal protein, C-25, was isolated from Cicer arietinum and purified by gel filtration. C-25 protein was tested using agar diffusion method against human pathogenic fungi of ATCC strains and against clinical isolates of Candida krusei, Candida tropicalis, and Candida parapsilosis, and MIC values determined were varied from 1.56 to 12.5 µg/mL. The SEM study demonstrated that C-25 induces the bleb-like surface changes, irregular cell surface, and cell wall disruption of the fungi at different time intervals. Cytotoxic activity was studied on oral cancer cells and normal cells. It also inhibits the growth of fungal strains which are resistant to fluconazole. It reduced the cell proliferation of human oral carcinoma cells at the concentration of 37.5 µg/mL (IC50) and no toxic effect was found on normal human peripheral blood mononuclear cells even at higher concentration of 600 µg/mL. It can be concluded that C-25 can be considered as an effective antimycotic as well as antiproliferative agent against human oral cancer cells.

Heparin binding carboxypeptidase E protein exhibits antibacterial activity in human semen.

Carboxypeptidase E (CPE) cleaves basic amino acid residues at the C-terminal end and involves in the biosynthesis of numerous peptide hormones and neurotransmitters. It was purified from human seminal plasma by ion exchange, heparin affinity and gel filtration chromatography followed by identification through SDS-PAGE and MALDI-TOF/MS analysis, which was further confirmed by western blotting. CPE was characterized as glycoprotein by Periodic Acid Schiff (PAS) staining and treating with deglycosylating enzyme N-glycosidase F. The interaction of CPE with heparin was illustrated by surface plasmon resonance (SPR) and in silico interaction analysis. The association constant (KA) and dissociation constant (KD) of CPE with heparin was determined by SPR and found to be 1.06 × 10(5)M and 9.46 × 10(-6)M, respectively. It was detected in human spermatozoa also by western blotting using mouse anti-CPE primary antibody. 20-100 µg/ml concentration of CPE was observed as highly effective in killing Escherichia coli by colony forming unit (CFU) assay. We suggest that CPE might act not only in the innate immunity of male reproductive tract but also regulate sperm fertilization process by interacting heparin.

Three low molecular weight cysteine proteinase inhibitors of human seminal fluid: purification and enzyme kinetic properties.

The cystatins form a superfamily of structurally related proteins with highly conserved structural folds. They are all potent, reversible, competitive inhibitors of cysteine proteinases (CPs). Proteins from this group present differences in proteinase inhibition despite their high level of structural similarities. In this study, three cysteine proteinase inhibitors (CPIs) of low molecular weight were isolated from human seminal fluid (HSF) by affinity chromatography on carboxymethyl (CM)-papain-Sepharose column, purified using various chromatographic procedures and checked for purity on sodium-dodecyl PAGE (SDS-PAGE). Matrix-assisted laser desorption-ionization-time-of flight-mass spectrometry (MALDI-TOF-MS) identified these proteins as cystatin 9, cystatin SN, and SAP-1 (an N-terminal truncated form of cystatin S). All three CPIs suppressed the activity of papain potentially and showed remarkable heat stability. Interestingly SAP-1 also inhibits the activity of trypsin, chymotrypsin, pepsin, and PSA (prostate specific antigen) and acts as a cross-class protease inhibitor in in vitro studies. Using Surface Plasmon Resonance, we have also observed that SAP-1 shows a significant binding with all these proteases. These studies suggest that SAP-1 is a cross-class inhibitor that may regulate activity of various classes of proteases within the reproductive systems. To our knowledge, this is the first report about purification of CPIs from HSF; the identification of such proteins could provide better insights into the physiological processes and offer intimation for further research.

Sirtuin1: a promising serum protein marker for early detection of Alzheimer's disease.

Sirtuin (SIRT) pathway has a crucial role in Alzheimer's disease (AD). The present study evaluated the alterations in serum sirtuin1 (SIRT1) concentration in healthy individuals (young and old) and patients with AD and mild cognitive impairment (MCI). Blood samples were collected from 40 AD and 9 MCI patients as cases and 22 young healthy adults and 22 healthy elderly individuals as controls. Serum SIRT1 was estimated by Surface Plasmon Resonance (SPR), Western Blot and Enzyme Linked Immunosorbent Assay (ELISA). A significant (p<0.0001) decline in SIRT1 concentration was observed in patients with AD (2.27 ± 0.46 ng/µl) and MCI (3.64 ± 0.15 ng/µl) compared to healthy elderly individuals (4.82 ± 0.4 ng/µl). The serum SIRT1 concentration in healthy elderly was also significantly lower (p<0.0001) compared to young healthy controls (8.16 ± 0.87 ng/µl). This study, first of its kind, has demonstrated, decline in serum concentration of SIRT1 in healthy individuals as they age. In patients with AD and MCI the decline was even more pronounced, which provides an opportunity to develop this protein as a predictive marker of AD in early stages with suitable cut off values.

Development of peptide inhibitor as a therapeutic agent against head and neck squamous cell carcinoma (HNSCC) targeting p38alpha MAP kinase.

BACKGROUND: The p38alpha MAP kinase pathway is involved in inflammation, cell differentiation, growth, apoptosis and production of pro-inflammatory cytokines TNF-alpha and IL-1beta. The overproduction of these cytokines plays an important role in cancer. The aim of this work was to design a peptide inhibitor on the basis of structural information of the active site of p38alpha. METHODS: A tetrapeptide, VWCS as p38alpha inhibitor was designed on the basis of structural information of the ATP binding site by molecular modeling. The inhibition study of peptide with p38alpha was performed by ELISA, binding study by Surface Plasmon Resonance and anti-proliferative assays by MTT and flow cytometry. RESULTS: The percentage inhibition of designed VWCS against pure p38alpha protein and serum of HNSCC patients was 70.30 and 71.5%, respectively. The biochemical assay demonstrated the K(D) and IC50 of the selective peptide as 7.22 x 10(-9) M and 20.08 nM, respectively. The VWCS as inhibitor significantly reduced viability of oral cancer KB cell line with an IC50 value of 10 microM and induced apoptosis by activating Caspase 3 and 7. CONCLUSIONS: VWCS efficiently interacted at the ATP binding pocket of p38alpha with high potency and can be used as a potent inhibitor in case of HNSCC. GENERAL SIGNIFICANCE: VWCS can act as an anticancer agent as it potentially inhibits the cell growth and induces apoptosis in oral cancer cell-line in a dose as well as time dependent manner. Hence, p38alpha MAP kinase inhibitor can be a potential therapeutic agent for human oral cancer.

A novel antimicrobial peptide derived from modified N-terminal domain of bovine lactoferrin: design, synthesis, activity against multidrug-resistant bacteria and Candida.

Lactoferrin (LF) is believed to contribute to the host's defense against microbial infections. This work focuses on the antibacterial and antifungal activities of a designed peptide, L10 (WFRKQLKW) by modifying the first eight N-terminal residues of bovine LF by selective homologous substitution of amino acids on the basis of hydrophobicity, L10 has shown potent antibacterial and antifungal properties against clinically isolated extended spectrum beta lactamases (ESBL), producing gram-negative bacteria as well as Candida strains with minimal inhibitory concentrations (MIC) ranging from 1 to 8 µg/mL and 6.5 µg/mL, respectively. The peptide was found to be least hemolytic at a concentration of 800 µg/mL. Interaction with lipopolysaccharide (LPS) and lipid A (LA) suggests that the peptide targets the membrane of gram-negative bacteria. The membrane interactive nature of the peptide, both antibacterial and antifungal, was further confirmed by visual observations employing electron microscopy. Further analyses, by means of propidium iodide based flow cytometry, also supported the membrane permeabilization of Candida cells. The peptide was also found to possess anti-inflammatory properties, by virtue of its ability to inhibit cyclooxygenase-2 (COX-2). L10 therefore emerges as a potential therapeutic remedial solution for infections caused by ESBL positive, gram-negative bacteria and multidrug-resistant (MDR) fungal strains, on account of its multifunctional activities. This study may open up new approach to develop and design novel antimicrobials.

p38ß MAP kinase as a therapeutic target for pancreatic cancer.

Pancreatic cancer is very difficult to diagnose in its early stage. Molecular marker and imaging have not proven to be accurate modalities for screening of pancreatic cancer. This study aims to develop p38ß as a protein marker for pancreatic cancer and to design peptide inhibitor against the same. The serum p38ß level of pancreatic cancer (n = 35; 5.06 µg/mL) was twofold higher compared to that of the chronic pancreatitis (n = 10; 2.92 µg/mL) and matched normal control (n = 10; 2.86 µg/ml) (p < 0.0005). Peptide inhibitors were designed to inhibit the activity of p38ß and the kinetic assay had shown the dissociation constant, (K(D)) to be 3.16 × 10(-8) M and IC(50), 25 nM by Surface Plasmon Resonance (SPR) and Enzyme-Linked Immunosorbent Assay (ELISA), respectively. The peptide inhibitor also significantly reduced viability and induced cytotoxicity in Human Pancreatic carcinoma epithelial-like cell line (PANC-1) cells.

Structure based design and synthesis of peptide inhibitor of human LOX-12: in vitro and in vivo analysis of a novel therapeutic agent for breast cancer.

Human breast cancer cell proliferation involves a complex interaction between growth factors, steroid hormones and peptide hormones. The interaction of growth factors, such as epidermal growth factor (EGF), with their receptors on breast cancer cells can lead to the hydrolysis of phospholipids and release of fatty acid such as arachidonic acid, which can be further metabolized by cyclooxygenase (COX) and lipoxygenase (LOX) pathways to produce prostaglandins. The high concentration of prostaglandins has been associated with chronic inflammatory diseases and several types of human cancers. This is due to the over expression COX, LOX and other inflammatory enzymes. Ten peptides were designed and synthesized by solid phase peptide synthesis and analyzed in vitro for enzyme inhibition. Out of these peptides, YWCS had shown significant inhibitory effects. The dissociation constant (K(D)) was determined by surface plasmon resonance (SPR) analysis and was found to be 3.39 × 10(-8) M and 8.6 × 10(-8) M for YWCS and baicalein (positive control), respectively. The kinetic constant Ki was 72.45 × 10(-7) M as determined by kinetic assay. The peptide significantly reduced the cell viability of estrogen positive MCF-7 and estrogen negative MDA-MB-231 cell line with the half maximal concentration (IC(50)) of 75 µM and 400 µM, respectively. The peptide also induced 49.8% and 20.8% apoptosis in breast cancer cells MCF-7 and MDA-MB-231, respectively. The YWCS was also found to be least hemolytic at a concentration of 358 µM. In vivo studies had shown that the peptide significantly inhibits tumor growth in mice (p<0.017). This peptide can be used as a lead compound and complement for ongoing efforts to develop differentiation therapies for breast cancer.

Quantification of p38αMAP kinase: a prognostic marker in HNSCC with respect to radiation therapy.

BACKGROUND: Translation of early findings from basic research is aimed to benefit cancer therapeutics. We report the p38α level in serum of head and neck squamous cell carcinoma (HNSCC) patients indicating it as a prognostic marker and established its correlation with radiation therapy (RT). METHODS: The case-controlled study was performed on 120 HNSCC patients from whom 81 patients and 45 controls were statistically analyzed. The p38α estimation was done at pre-RT, during-RT and post-RT using a real time Surface Plasmon Resonance (SPR) technology, ELISA and western blot. RESULTS: HNSCC patients showed threefold increase in p38α level when compared to control (p value<0.0001). The estimated concentration of p38α in a temporal manner, before-RT, during-RT and post-RT was 0.61 ng/µl (95%CI: 0.53-0.69), 0.35 ng/µl (95%CI: 0.31-0.38) and 0.30 ng/µl (95%CI: 0.26-0.33), respectively. Among the 81 cases, 70 patients (86.42%) showed a declined p38α in response to RT as evaluated by SPR and were responding clinically (clinical tumor regression). CONCLUSIONS: This study showed elevated p38α level at cancer diagnosis and a statistically significant decline during-RT and post-RT periods. Hence, it can emerge as a prognostic marker supporting the candidature of p38α as a suitable serum marker in HNSCC.