Metabolic signals influence cell-fate decisions in Dictyostelium discoideum.

Nutrient-sensing plays a crucial role in maintaining cellular energy and metabolic homeostasis. Perturbations in sensing pathways are associated with a wide variety of pathologies, especially metabolic diseases. Very little is understood about sensing fluctuations in nutrients and how this information is integrated into physiological and metabolic adaptation that could further affect cell-fate decisions during differentiation in Dictyostelium discoideum (henceafter, Dictyostelium). Glucose is the primary metabolic fuel among all nutrients. Carbohydrates, lipids and proteins ultimately breakdown into glucose, which is further used for providing energy. The maintenance of optimum glucose levels is important for efficient cell-survival. Glucose is not only a nutrient, but also a signaling molecule influencing cell growth and differentiation in Dictyostelium. Modulation of endogenous glucose levels either by varying exogenous glucose levels or genetic overexpression or deletion of genes involved in glucose signaling lead to changes in endogenous metabolite levels such as ADP/ATP ratio, NAD+ /NADH ratio, cAMP and ROS levels which further influence cell-fate decisions. Here, we show that AMPKα and Sir2D are components of glucose-signaling pathway in Dictyostelium which adjust cell metabolism interdependently in response to nutrient-status and promote cell-fate decisions.

Oral Microbiota as a Diagnostic Biomarker of Digestive Cancer: A Systematic Review.

AIM: This article aimed to review the association of oral microbiota with digestive cancer (DC). BACKGROUND: Oral microbiota is one of the most complex ecosystems in our body. The mouth, from which the digestive system starts, may be a source of an abundant taxonomic group of microbiotas that travel to the digestive system followed by growth, reproduction, and settlement, forming a complex microecological environment causing systemic and gastrointestinal (GI) disease. REVIEW RESULTS: A total of 14 articles were chosen for review. Most studies were case-control. Both positive and negative associations were seen between oral microbiome and DC. CONCLUSION: Digestive cancer may be associated with distinctive oral microbial character. CLINICAL SIGNIFICANCE: The present systematic review enlightens the risk of digestive carcinoma with oral microbiota that may act as a biomarker for early diagnosis of DC in a more comfortable, acceptable, and noninvasive way. How to cite this article: Ikbal SKA, Yadav SK, Mehrotra R, et al. Oral Microbiota as a Diagnostic Biomarker of Digestive Cancer: A Systematic Review. J Contemp Dent Pract 2023;24(11):902-911.

Association of Catechol-O-Methyltransferase Gene Polymorphisms and Haplotypes in the Levodopa-Induced Adverse Events in Subjects with Parkinson's Disease.

The presence of dyskinesia is the most common side effect of chronic administration of levodopa in Parkinson's disease (PD) subjects. Genetic polymorphisms in levodopa metabolizing gene, catechol-O-methyl transferase (COMT), is shown to influence the inter-individual variability in drug response and adverse events. In the present study, the association of COMT rs6269, rs4633, rs4818, and rs4680 polymorphisms and haplotypes on pharmacokinetics and adverse events with levodopa was investigated in 150 PD patients. The age of onset of PD was 58.00 ± 10 yrs. The most common side effect faced by 78% of the subjects was dyskinesia. The AUC of levodopa was found to be significantly higher in subjects with dyskinesia (1695 ± 113 ng/ml/hr, p < 0.0001) than those without dyskinesia (1550 ± 122 ng/ml/hr). We found that the frequency of subjects presenting dyskinesia was significantly higher in subjects carrying variant genotype of COMT rs6269, rs4633, and rs4680 than that with wild genotype and these subjects presented higher AUC of levodopa. In addition, in subjects with dyskinesia, the AUC of levodopa was found to be significantly higher with low COMT (ACCG) haplotype. The association of COMT rs6269, COMT rs4633, COMT rs4818, and COMT rs4680 variant genotypes with the risk of dyskinesia due to levodopa therapy showed an ROC AUC of 0.67 indicating the moderate prediction of dyskinesia (p = 0.0021) with these COMT variants. In conclusion, PD subjects carrying the variant genotypes of COMT strongly influence high levodopa-induced dyskinesia. Hence the genotyping of COMT before the levodopa therapy will be useful to reduce the adverse events associated with the chronic levodopa treatment.

Association of polymorphism c.-124G>A and c.-16 C>T in the promoter region of human INHA gene with altered sperm parameters; A pilot study.

OBJECTIVE: The objective of this was to demonstrate the association of Inhibin α (INHα) c.-124G>A and INHα-c.-16 C>T polymorphisms with altered sperm parameters in a selected male population of Karachi, Pakistan. STUDY DESIGN & SETTINGS: In this pilot study, male subjects were stratified on the basis of the WHO criteria for altered sperm parameters; 83 (cases-altered sperm parameters) and 30 (controls-normal sperm parameters) subjects were included for analysis of INHα-c.124G>A polymorphism and 88 (cases) and 38 (controls) were analysed for INHα -c-16 C>T polymorphism. Genotyping of INHα-c.-124G>A and INHα-c.-16 C>T was performed by PCR-RFLP, genotype distribution in Hardy-Weinberg equilibrium was evaluated by binary logistic regression model. RESULTS: For the c.-124G>A polymorphism in INHα gene, frequency of the three major genotypes in controls was: GG: 80.0%, GA: 20.0% and AA: 0% and in cases was: GG: 59.0%, GA: 30.2% and AA: 10.8%. The GG genotype was significantly associated with male infertility (P < .045, OR = 2.776, 95% CI = 1.025-7.513) while the GA genotype was not significantly associated with infertility (P < .290 OR = 0.580, 95% CI = 0.211-1.593). Frequency of mutant AA genotype was 10.8% in cases (altered sperm parameters) and absent (0%) in normal sperm parameter (controls). The frequencies of three major genotypes CC, CT and TT did not show any significant difference between cases and controls (P > .05). CONCLUSION: The results from our study exhibited a significant association of c.-124G>A polymorphism in the INHα gene promoter region with male infertility in the Pakistani population. A significant association of c.-16 C>T polymorphism with male infertility, however, was not observed. Further large-scale studies should be conducted to confirm this association.

Impact of exploitative leadership on psychological distress: A study of nurses.

AIM: This study tested the (a) impact of exploitative leadership on psychological distress of nurses via negative affectivity and (b) moderating role of psychological detachment from work between exploitative leadership and negative affectivity. BACKGROUND: Destructive leadership, particularly exploitative leadership, has been less studied earlier in nursing research. Additionally, underlying mechanisms and boundary conditions that exist between exploitative leadership and negative employee outcomes were also missing in the nursing literature. METHODS: This is a quantitative study in which temporally segregated data were collected from nurses (N = 231) working in Pakistani hospitals through questionnaires. RESULTS: Negative affectivity mediates the relationship between exploitative leadership and psychological distress among nurses, and psychological detachment from work weakens exploitative leadership and negative affectivity relationship. CONCLUSIONS: Exploitative leadership yields negative employee outcomes in the form of negative affectivity and psychological distress; however, these negative outcomes can be reduced through psychological detachment from work. IMPLICATIONS FOR NURSING MANAGEMENT: It is among the pioneer studies to unveil the exploitative side of leadership and its negative consequences for nurses. Psychological distress among nurses can be reduced by discouraging leader exploitative behaviour. Nurses could utilize psychological detachment from work as a tool to reduce negative outcomes of leader exploitative behaviour.

Nigella sativa Oil Reduces Extrapyramidal Symptoms (EPS)-Like Behavior in Haloperidol-Treated Rats.

The symptoms of Parkinsonism and oral dyskinesia have been showing to be induced by neuroleptics that significantly affect its clinical use. In this study, we investigate whether Nigella sativa-oil (NS) (black cumin seeds)-a traditional medicine used for the seizure treatment in eastern country-may reduce the haloperidol (HAL)-induced extrapyramidal symptoms (EPS)-like behavior in rats. After combine treatment with HAL (1 mg/kg) on NS (0.2 ml/rat), rats displayed a significant decreased EPS-like behavior including movement disorders and oral dyskinesia as compared to controls. Immunohistochemical analysis indicates that NS reduced astrogliosis in caudate and accumbens nuclei. These results suggest that NS may consider as an adjunct to antipsychotics to reduce the EPS-like side effect.

Frequency of FMR1 gene mutation and CGG repeat polymorphism in intellectually disabled children in Pakistan.

Fragile X syndrome is considered the most common heritable form of X-linked intellectual disability (ID). The syndrome is caused by silencing of the fragile X mental retardation 1 gene (Xq27.3) due to hypermethylation. This mutation results in absence or deficit of its protein product, the fragile X mental retardation protein (FMRP) that affects synaptic plasticity in neurons, hence leads to brain dysfunction. The syndrome is widely distributed throughout the world. This study reported for the first time the frequency of the fragile X mental retardation 1 gene mutations in intellectually disabled children in Pakistan. We recruited 333 intellectually disabled children and 250 normal children with age ranging from 5 to 18 years for this study. Genomic DNA was extracted from peripheral blood and full mutations were identified by methylation sensitive PCR using primers corresponding to modified methylated and unmethylated DNA. Southern blot was used for confirmation of the results. The frequency of fragile X syndrome with full mutation was found as 4.8%. It was 6.5% in males as opposed to 0.9% in females; 29 CGG repeats were found as the most common allele; 31.5% in the intellectually disabled and 34% in control subjects. In Pakistan intellectual disability is considered as a social stigma for the individuals and their families. Due to lack of knowledge and cultural background people make such patients and families isolated. This study will increase public awareness about the intellectual disability and importance of prenatal screening and genetic counseling for vulnerable families.

Surgical Lip Repositioning in Search of Aesthetics - A Case Series.

INTRODUCTION: The gummy smile (GS) or excessive gum visibility (EGV) is an aesthetic concern that affects an individual's attractiveness and personality. TREATMENT PLANNING: Lip Repositioning surgery (LRP) is a less invasive surgery that can be attributed to treating EGV due to hypermobile lip muscles or mild-to-moderate vertical maxillary excess (VME). Three patients went through LRP surgery by stripping overlying mucosa from the buccal vestibule, followed by suturing the lip mucosa to the mucogingival junction (MGJ), creating shallow vestibule and restricted muscle pull and reducing gingival visibility (GV) during a smile. FOLLOWUP: Three months of follow-up showed a satisfactory result with 3.67 ± 0.58 mm mean reduction in GV.

Association of catechol-o-methyltransferase gene polymorphism with preeclampsia and biomarkers of oxidative stress: Study protocol for a prospective case-control study in Pakistan.

BACKGROUND: Preeclampsia is one of the three leading causes of worldwide maternal mortality. Oxidative stress-mediated endothelial damage is expected to be an ultimate common mechanism in the pathophysiology of preeclampsia. The role of bioamines is also well-established in the induction of preeclampsia. This project is aimed to understand the factors which may affect the induction, progression, and aggravation of preeclampsia and oxidative stress during pregnancy. This study will explore the methylation pattern of the Catechol-O-methyltransferase gene to determine its role in the pathogenesis of preeclampsia, association of Val158Met polymorphism with a wide range of oxidative stress biomarkers, major antioxidants vitamins, and blood pressure regulating amines in preeclamptic Pakistani women. METHODS AND ANALYSIS: In this prospective case-control study, 85 preeclamptic and 85 normotensive pregnant women will be recruited in their third trimesters. DNA will be extracted from peripheral blood and Val158Met polymorphism in the Catechol-O-methyltransferase gene will be examined on PCR amplified product digested with Hin1II (NlaIII) restriction enzyme, further validated by Sanger sequencing. Methylation-sensitive PCR will also be performed. Oxidative stress biomarkers, antioxidant vitamins, bioamines, and catechol-O-methyltransferase levels will be measured by ELISA. The data will be used to correlate maternal and fetal outcomes in both groups. DISCUSSION: This study will help to identify and understand the multifactorial path and cause-effect relationship of gene polymorphism, oxidative stress biomarkers, major antioxidants vitamins, and blood pressure regulating amines in the pathogenesis and aggravation of preeclampsia in the Pakistani population. The outcome of this project will be particularly helpful in reducing the incidence of preeclampsia and further improving its management.

Secondary open-angle pigmentary glaucoma resulting from a single-piece hydrophobic intraocular lens in the sulcus.

The case report of a 68-year-old man with a single-piece hydrophobic intraocular lens (IOL) implanted in the sulcus with posterior capsular rent in the right eye inducing secondary open-angle pigmentary glaucoma without individual hereditary steroid susceptibility. The clinical and diagnostic evaluations of the patient were thoroughly and specifically carried out. The unilateral pseudophakic open-angle pigmentary glaucoma developed in the long course in the context of rubbing of the haptics and optic of a hydrophobic IOL implanted in the sulcus, against the posterior surface of the iris, resulting in pigment dispersion, trabecular inflammation, and aqueous outflow obstruction. Although the clinical findings of our case were very similar to that of pigmentary glaucoma, the distinction between the two conditions was still quite easy, considering that pigmentary glaucoma is a bilateral disorder predominantly affecting young myopic men with Krukenberg's spindle and increased incidence of steroid responsiveness. It has been clearly distinguished from steroid-induced glaucoma based on the pigmented trabecular meshwork.

Food Environments and Their Influence on Food Choices: A Case Study in Informal Settlements in Nairobi, Kenya.

The food environments that people have access to shape their food choices. The purpose of this study was to use mixed methods to characterize the external food environment in informal settlements in Nairobi, Kenya and to examine the individual factors that influence the way in which women interact with those environments to make food choices. We used a combination of food environment assessments (vendor mapping, collection of food prices, food quality assessments) and five focus group discussions with women (n = 26) in four villages within two informal settlements in Nairobi (Mukuru and Kibera) to better understand the drivers of food choice. We found a large number (n = 1163) of vendors selling a variety of food within the settlements. The highest number of vendors were selling fruits and/or vegetables; however, there was limited diversity of fruits available. Animal-source foods were considered relatively expensive as compared to plant-based foods, including prepared fried snacks. We found that the way women interacted with their food environments was influenced by individual factors such as income, time, convenience, and preferences. Our findings suggest that interventions targeting both the external food environment as well as individual factors such as income will be necessary to support healthy diets among low-income populations living in informal settlements in Kenya.

MTHFR-c 677C>T polymorphism and male infertility: An analysis in a cohort of Pakistani men.

OBJECTIVE: To analyze existence of an association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with male infertility. MATERIALS AND METHODS: A case-control study was conducted from June 2017 to August 2018 in which 88 infertile and 40 fertile were recruited. Polymerase chain reaction (PCR) - restriction fragment length polymorphism (RFLP) assay was carried out to study the allelic frequency of C677T polymorphism. The differences in allelic and genotypic frequencies of C677T locus between fertile and infertile groups were evaluated by the Pearson chisquare test. A logistic regression model was used to calculate Odds ratios and 95% confidence intervals, p value<0.05 was considered significant. The Hardy-Weinberg equilibrium was tested using HWE software. RESULTS: In infertile subjects, frequency distribution of CC allele was (60.2%), the CT allele was (30.7%) the TT allele was (9.1%) and in the fertile controls the frequency was CC allele (75%), CT allele (20%) and TT allele (5%) respectively. Analysis revealed MTHFR 677 CC genotype associated significantly with male infertility (p<.046, OR=2.385; 95% CI=1.014-5.608); Frequency of CT (30.7%) and TT (9.1) genotypes were higher in infertile men as compared to CT (20%) TT (5%) in fertile controls but statistically these were not significantly different (p=0.097; OR=0.455; CI=0.179-1.153 and p=0.431; OR=0.526; CI=0.107-2.599 respectively). Significant association of age and BMI with MTHFR genotypes and infertility was observed. CONCLUSION: Our results showed that MTHFR C677T polymorphism is not a risk factor for male infertility in our Pakistani population.

The Influence of Food Environments on Food Security Resilience during the COVID-19 Pandemic: An Examination of Urban and Rural Difference in Kenya.

Hunger and food insecurity has worsened due to the COVID-19 pandemic. The types of food environments (e.g., natural/built) that people can access may improve household resilience to food-system shocks. This paper examines (1) urban and rural differences in the perceived influence of the COVID-19 pandemic on agricultural, livelihoods, food environment attributes, diets; and (2) whether access to different food environments was associated with food security. A two-part telephonic survey (COVID-19 Surveillance Community Action Network Food Systems Tool and Household Food Insecurity Access Scale) was conducted in Western Kenya (n = 173) and an informal settlement in Nairobi (n = 144) in January/February 2021. Limitations on the acquisition of farm inputs and movement restrictions had an adverse impact on agriculture and food sales. Urban residents reported a more significant impact on livelihoods (97% vs. 87%, p < 0.001), with day laborers being the most impacted. Rural respondents reported access to significantly more food environments and lower food insecurity. Multiple linear regression analysis revealed that younger respondents, ≤1 income source, had more difficulty acquiring food, decreased access to cultivated environments, and increased access to informal markets were predictors for higher food insecurity. These data indicate that access to specific types of food environments may improve household resilience.

Impressing for popularity and influence among peers: The connection between employees' upward impression management and peer-rated organizational influence.

To investigate how employees' impression management behavior, targeted upward at organizational leaders, relates to their peer-rated organizational influence, this study considers both a mediating role of peer-rated workplace popularity and a moderating role of self-rated social dominance orientation. Multisource, three-wave data from employees and their peers in the power-distant, collectivistic country of Pakistan reveal that upward impression management behavior, despite raising some potential organizational concerns, is associated with peer-rated workplace popularity for employees, who in turn can wield greater influence over colleagues. The mediating role of peer-rated workplace popularity also is more prominent to the extent that employees accept social hierarchies, because this orientation makes their use of upward impression management tactics to advance their own and their peers' personal interests more purposeful.

Bridging the Breach: Using Positive Affectivity to Overcome Knowledge Hiding after Contract Breaches.

With a basis in conservation of resources theory, this study investigates the relationship between employees' exposure to perceived contract breaches and their job performance, while also considering the mediating role of knowledge hiding and the moderating role of positive affectivity. Multisource, three-wave data from employees and their peers in Pakistani organizations reveal that breaches in the psychological contract hinder job performance, because employees respond with an unwillingness to contribute valuable knowledge to execute their job tasks. This mediating role of knowledge hiding is mitigated if employees can draw from their own positive affectivity trait. This study accordingly identifies a key factor, intentional attempts to conceal knowledge requested by other members, that can backfire and make employees suffer doubly: from unfulfilled organizational promises and from lower performance. It also reveals how this risk might be contained, that is, by encouraging employees' positive affect.

Can mindfulness overcome the effects of workplace ostracism on job performance?

With a basis in the transactional theory of stress and coping, this study investigates the relationship between employees' exposure to workplace ostracism and their job performance, while also considering the mediating role of acquiescence silence and the moderating role of mindfulness. Multisource, three-wave data from employees and their peers in Pakistani organizations reveal that ostracism in the workplace hinders job performance because employees passively withhold relevant ideas about their work due to feelings of acquiescence. The mediating role of acquiescence silence is mitigated if employees can draw from their mindfulness trait. This study accordingly identifies a key mechanism - the passive withholding of pertinent ideas, based on submission - by which workplace ostracism hampers job performance, and it reveals how this process might be contained by encouraging employees' receptive attention and awareness focused on present experiences.

Relationship Between Problematic Social Media Usage and Employee Depression: A Moderated Mediation Model of Mindfulness and Fear of COVID-19.

Social media plays a significant role in modern life, but excessive use of it during the COVID-19 pandemic has become a source of concern. Supported by the conservation of resources theory, the current study extends the literature on problematic social media usage during COVID-19 by investigating its association with emotional and mental health outcomes. In a moderated mediation model, this study proposes that problematic social media use by workers during COVID-19 is linked to fear of COVID-19, which is further associated with depression. The current study tested trait mindfulness as an important personal resource that may be associated with reduced fear of COVID-19 despite problematic social media use. The study collected temporally separate data to avoid common method bias. Pakistani employees (N = 267) working in different organizations completed a series of survey questionnaires. The results supported the moderated mediation model, showing that problematic social media use during the current pandemic is linked to fear of COVID-19 and depression among employees. Furthermore, trait mindfulness was found to be an important buffer, reducing the negative indirect association between problematic social media use and depression through fear of COVID-19. These results offer implications for practitioners. The limitations of this study and future research directions are also discussed.

Does Despotic Leadership Harm Employee Family Life: Exploring the Effects of Emotional Exhaustion and Anxiety.

Research has not focused on the negative effects of despotic leadership on subordinates' life satisfaction and the interface between work and family. Drawing on the Conservation of Resources theory, this research investigates the mediating effect of emotional exhaustion through which despotic leadership transcends from the workplace to subordinates' personal lives, resulting in work-family conflict and decreased life satisfaction. The research also examines the moderating effect of subordinates' anxiety on the relationship of their perceptions of despotic leadership with work-family conflict and life satisfaction. Three waves of time-lagged data was collected from 224 book sellers who work in publishing houses. We used Hayes' PROCESS to test moderation and SEM to test mediation. The results of the study suggest that despotic leadership is related to work-family conflict via emotional exhaustion, but offer no support for its relationship with life satisfaction. As expected, when subordinates' anxiety increases, the positive relationship between a supervisor's despotism and his or her subordinates' work-family conflict and the negative relationship between despotic leadership and life satisfaction both strengthen. The results suggest that despotic leaders harm their subordinates' non-work lives, and these effects intensify when subordinates have high levels of anxiety. These findings have important implications for service organizations in mitigating the negative effects of despotic leadership by minimizing subordinates' anxiety through coping mechanisms and giving reward and incentives.

Jeopardies of Aversive Leadership: A Conservation of Resources Theory Approach.

The research on the dark side of leadership is still in its infancy. We have contributed to this line of research by proposing that work alienation acts as an underlying mechanism through which aversive leadership results in reduced job performance. We further propose that psychological capital (PsyCap) acts as an important personal resource that reduces the negative effects of aversive leadership in the form of work alienation. The proposed model gets its support from the conversation of resources theory given by Hobfoll (1989) which suggests that stressful situation like an aversive leadership results in the loss of employee resources as a result of that he/she indulges in work alienation and shows poor job performance to retain back the lost resources. People with better personal resources in the form of PsyCap are better able to cope-up with the aversive leader behavior and make them able to avoid work alienation. It is a time-lagged study. The data for the current study was collected from 321 employees working in the service sector organizations, particularly universities, banks and telecom organizations, through personally administered questionnaires. The results supported the mediation and moderation hypothesis. Limitations and future research along with theoretical and practical implications are given at the end.