Integrative Review of Workplace Health Promotion in the Business Process Outsourcing Industry: Focus on the Philippines.

Objective: The Business Process Outsourcing (BPO) industry in the Philippines has experienced substantial growth, making a significant contribution to the country's economy. However, concerns about work-related health and safety issues have emerged, necessitating effective workplace health promotion strategies for BPO employees. Study design: An integrative review of relevant literature was conducted to explore workplace health promotion in the BPO sector. Methods: The search included quantitative, qualitative, and mixed-method studies, pertinent laws, policies, news articles, and reports published between 2000 and 2022. The scope was intentionally broad to encompass a diverse range of relevant evidence related to workplace health in this field. Articles published both in the English and Filipino languages were considered. Results: Findings revealed that BPO workers face risks related to physical and psychological stress, sleep disturbances, and occupational diseases owing to the unique challenges inherent to the nature of their jobs. While there are existing occupational health and labor laws, compliance among BPO companies remains a problem, and only a few organizations offer comprehensive wellness programs. Building upon the available evidence, a conceptual framework was developed to provide guidance for enhancing workplace health promotion initiatives specifically designed for BPOs in the country. Conclusion: Workplace health promotion is vital to warrant the health and safety of BPO workers. This study offers evidence-based recommendations for implementing effective well-being strategies, highlighting the importance of collaboration among employers, employees, and society to prioritize employee health in the workplace.

The application of behavioral change theories in addressing vaccine hesitancy: A Literature Review.

Vaccination is vital in combating infectious diseases, including COVID-19. Nevertheless, vaccine hesitancy poses a substantial obstacle to achieving high vaccination rates. This study investigated the determinants of vaccine hesitancy using behavioral change theories and proposes a comprehensive conceptual framework to address this challenge.The paper conducted a review of several behavior change theories relevant to understanding vaccine hesitancy. The health belief model (HBM) highlighted the importance of individuals' perceptions of the effectiveness of health behaviors and their perceived susceptibility to illness. The social cognitive model (SCT) underscored the role of personal experiences, environmental factors, and social support in shaping health behaviors. The theory of reasoned action and planned behavior (TRA) suggested that attitudes and subjective norms are crucial in determining behavioral intentions. The transtheoretical model (TTM) outlined stages of behavior change, while the socio-ecological model (SEM) considered factors at individual, relationship, community, and societal levels. Comprehending vaccine hesitancy is essential for developing effective strategies to promote vaccine acceptance. This study, which examined vaccine hesitancy through various behavior change theories, sought to shed light on the factors influencing vaccine hesitancy among Filipinos. The resulting conceptual framework offers guidance for future interventions aimed at addressing vaccine hesitancy and ultimately improving vaccination rates.

Autoantibodies Against Bestrophin in Non-Paraneoplastic Acute Exudative Polymorphous Vitelliform Maculopathy.

Acute exudative polymorphous vitelliform maculopathy (AEPVM) has recently been identified as a paraneoplastic manifestation of various cancers. Yet, the first reported cases of AEPVM in the literature were reported in seemingly healthy individuals. It is not clear whether those individuals harbored unidentified mutations or occult cancers, or truly represented a separate subset of AEPVM. Here, we report two cases of mutation-negative, autoantibody-positive non-paraneoplastic AEPVM. We present multimodal ocular imaging to demonstrate the presentation of this subset of AEPVM. [Ophthalmic Surg Lasers Imaging Retina 2024;55:51-54.].

Neovascularization against autologous SLET donor grafts despite successful corneal epithelialization and graft adherence.

PURPOSE: To report a case of neovascularization against autologous grafts after simple limbal epithelial transplantation (SLET) despite successful corneal epithelialization, as well as its subsequent regression without intervention. METHODS: A case report and review of the literature. RESULTS: A 52-year-old woman underwent uncomplicated autologous SLET for asymmetric limbal stem cell deficiency (LSCD) in the left eye. One month after the surgery, the patient had successful adherence of the graft and corneal epithelialization; however, new neovascularization developed in the left eye towards the graft sites. With only a slow taper of topical prednisolone acetate and polymyxin b/trimethoprim, the neovascularization regressed to ghost vessels over the following three months with improvement of her LSCD symptoms and increased clarity of her cornea. CONCLUSION: The limbus does not enjoy relative immune privilege like other parts of the eye; therefore, autologous limbal stem cell transplantation (along with the minimal immune response generated) is valuable for restoration of the ocular surface. Here, we describe neovascularization against autologous donor grafts despite an otherwise uncomplicated surgery and expected epithelialization course. Inflammation-mediated angiogenesis likely initiated the neovascularization, suggesting that immune mediators of inflammation may be inadvertently part of the graft tissue in bilateral LSCD.

Scleral ectasia stabilization following intra-arterial chemotherapy in an eye with recurrent retinoblastoma.

Purpose: To report a case of recurrent retinoblastoma following transpupillary thermotherapy (TTT) with development of scleral ectasia, as well as their successful treatment with intra-arterial chemotherapy. Observations: A 15-month-old girl with bilateral retinoblastoma presented with recurrent retinoblastoma and associated scleral ectasia with concern for extraocular extension after receiving multiple round of systemic chemotherapy and TTT. Given her negative systemic evaluation, decision was made to pursue intra-arterial chemotherapy. After completion of six rounds of 3-agent intra-arterial chemotherapy, the recurrent retinoblastoma had completely regressed and the scleral ectasia had improved and fibrosed. Conclusions and importance: The sclera is classically viewed as hyperthermy-resistant to TTT. Here, we describe scleral ectasia due to aggressive TTT with recurrence of the retinoblastoma. Our treatment with intra-arterial chemotherapy not only caused complete regression of the recurrent retinoblastoma, but it also contributed to the stabilization and improvement of the weakened scleral.

The Cost of Standard and Complex Pars Plana Vitrectomy for Retinal Detachment Repair Exceeds Its Reimbursement.

OBJECTIVE: To measure the total costs and reimbursements associated with standard and complex pars plana vitrectomy using time-driven activity-based costing (TDABC). DESIGN: Economic analysis at a single academic institution. SUBJECTS: Patients who underwent standard or complex pars plana vitrectomy (PPV; Current Procedural Terminology codes 67108 and 67113) at the University of Michigan in the calendar year 2021. METHODS: Process flow mapping for standard and complex PPVs was used to determine the operative components. The internal anesthesia record system was used to calculate time estimates, and financial calculations were constructed from published literature and internal sources. A TDABC analysis was used to determine the costs of standard and complex PPVs. Average reimbursement was based on Medicare rates. MAIN OUTCOME MEASURES: The primary outcomes were the total costs for standard and complex PPVs and the resulting net margin at current Medicare reimbursement levels. The secondary outcomes were the differential in surgical times, costs, and margin for standard and complex PPV. RESULTS: Over the 2021 calendar year, a total of 270 standard and 142 complex PPVs were included in the analysis. Complex PPVs were associated with significantly increased anesthesia time (52.28 minutes; P < 0.001), operating room time (51.28 minutes; P < 0.0001), surgery time (43.64 minutes; P < 0.0001), and postoperative time (25.95 minutes; P < 0.0001). The total day-of-surgery costs were $5154.59 and $7852.38 for standard and complex PPVs, respectively. Postoperative visits incurred an additional cost of $327.84 and $353.86 for standard and complex PPV, respectively. The institution-specific facility payments were $4505.50 and $4935.14 for standard and complex PPV, respectively. Standard PPV yielded a net negative margin of -$976.93, whereas complex PPV yielded a net negative margin of -$3271.10. CONCLUSIONS: This analysis demonstrated that Medicare reimbursement is inadequate in covering the costs of PPV for retinal detachment, with a particularly large negative margin for more complex cases. These findings demonstrate that additional steps may be necessary to mitigate adverse economic incentives so that patients continue to have timely access to care to achieve optimal visual outcomes after retinal detachment. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Hemorrhagic Occlusive Retinal Vasculitis Associated With Triamcinolone-Moxifloxacin Use During Uncomplicated Cataract Surgery.

This case series describes the outcomes of cataract extraction with intraocular lens placement in 2 patients.

Iatrogenic Paracentral Visual Field Defect After Pars Plana Vitrectomy for Macula-On Retinal Detachment Repair.

Perfluorocarbon liquid (PFCL) is an important adjunct in pars plana vitrectomy (PPV) for complex retinal detachment (RD). Complete removal of PFCL is critical to prevent retinal inflammation and cellular toxicity, but removal is not risk-free. We report a case of a new postoperative onset paracentral visual field defect after PPV with PFCL use for treatment of a macula-on RD. We present pre- and postoperative imaging that suggests a likely perioperative iatrogenic cause. [Ophthalmic Surg Lasers Imaging Retina 2022;53:644-646.].

NTS Prlh overcomes orexigenic stimuli and ameliorates dietary and genetic forms of obesity.

Calcitonin receptor (Calcr)-expressing neurons of the nucleus tractus solitarius (NTS; CalcrNTS cells) contribute to the long-term control of food intake and body weight. Here, we show that Prlh-expressing NTS (PrlhNTS) neurons represent a subset of CalcrNTS cells and that Prlh expression in these cells restrains body weight gain in the face of high fat diet challenge in mice. To understand the relationship of PrlhNTS cells to hypothalamic feeding circuits, we determined the ability of PrlhNTS-mediated signals to overcome enforced activation of AgRP neurons. We found that PrlhNTS neuron activation and Prlh overexpression in PrlhNTS cells abrogates AgRP neuron-driven hyperphagia and ameliorates the obesity of mice deficient in melanocortin signaling or leptin. Thus, enhancing Prlh-mediated neurotransmission from the NTS dampens hypothalamically-driven hyperphagia and obesity, demonstrating that NTS-mediated signals can override the effects of orexigenic hypothalamic signals on long-term energy balance.

Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort.

Mutations in the melanocortin 4 receptor gene (MC4R) are associated with obesity but little is known about the prevalence and impact of such mutations throughout human growth and development. We examined the MC4R coding sequence in 5,724 participants from the Avon Longitudinal Study of Parents and Children, functionally characterized all nonsynonymous MC4R variants and examined their association with anthropometric phenotypes from childhood to early adulthood. The frequency of heterozygous loss-of-function (LoF) mutations in MC4R was ~1 in 337 (0.30%), considerably higher than previous estimates. At age 18 years, mean differences in body weight, body mass index and fat mass between carriers and noncarriers of LoF mutations were 17.76 kg (95% CI 9.41, 26.10), 4.84 kg m-2 (95% CI 2.19, 7.49) and 14.78 kg (95% CI 8.56, 20.99), respectively. MC4R LoF mutations may be more common than previously reported and carriers of such variants may enter adult life with a substantial burden of excess adiposity.

Integrative Biology of Diabetic Retinal Disease: Lessons from Diabetic Kidney Disease.

Diabetic retinal disease (DRD) remains the most common cause of vision loss in adults of working age. Progress on the development of new therapies for DRD has been limited by the complexity of the human eye, which constrains the utility of traditional research techniques, including animal and tissue culture models-a problem shared by those in the field of kidney disease research. By contrast, significant progress in the study of diabetic kidney disease (DKD) has resulted from the successful employment of systems biology approaches. Systems biology is widely used to comprehensively understand complex human diseases through the unbiased integration of genetic, environmental, and phenotypic aspects of the disease with the functional and structural manifestations of the disease. The application of a systems biology approach to DRD may help to clarify the molecular basis of the disease and its progression. Acquiring this type of information might enable the development of personalized treatment approaches, with the goal of discovering new therapies targeted to an individual's specific DRD pathophysiology and phenotype. Furthermore, recent efforts have revealed shared and distinct pathways and molecular targets of DRD and DKD, highlighting the complex pathophysiology of these diseases and raising the possibility of therapeutics beneficial to both organs. The objective of this review is to survey the current understanding of DRD pathophysiology and to demonstrate the investigative approaches currently applied to DKD that could promote a more thorough understanding of the structure, function, and progression of DRD.

Paraventricular Calcitonin Receptor-Expressing Neurons Modulate Energy Homeostasis in Male Mice.

The paraventricular nucleus of the hypothalamus (PVH) is a heterogeneous collection of neurons that play important roles in modulating feeding and energy expenditure. Abnormal development or ablation of the PVH results in hyperphagic obesity and defects in energy expenditure whereas selective activation of defined PVH neuronal populations can suppress feeding and may promote energy expenditure. Here, we characterize the contribution of calcitonin receptor-expressing PVH neurons (CalcRPVH) to energy balance control. We used Cre-dependent viral tools delivered stereotaxically to the PVH of CalcR2Acre mice to activate, silence, and trace CalcRPVH neurons and determine their contribution to body weight regulation. Immunohistochemistry of fluorescently-labeled CalcRPVH neurons demonstrates that CalcRPVH neurons are largely distinct from several PVH neuronal populations involved in energy homeostasis; these neurons project to regions of the hindbrain that are implicated in energy balance control, including the nucleus of the solitary tract and the parabrachial nucleus. Acute activation of CalcRPVH neurons suppresses feeding without appreciably augmenting energy expenditure, whereas their silencing leads to obesity that may be due in part due to loss of PVH melanocortin-4 receptor signaling. These data show that CalcRPVH neurons are an essential component of energy balance neurocircuitry and their function is important for body weight maintenance. A thorough understanding of the mechanisms by which CalcRPVH neurons modulate energy balance might identify novel therapeutic targets for the treatment and prevention of obesity.

Photoreceptor metabolic reprogramming: current understanding and therapeutic implications.

Acquired and inherited retinal disorders are responsible for vision loss in an increasing proportion of individuals worldwide. Photoreceptor (PR) death is central to the vision loss individuals experience in these various retinal diseases. Unfortunately, there is a lack of treatment options to prevent PR loss, so an urgent unmet need exists for therapies that improve PR survival and ultimately, vision. The retina is one of the most energy demanding tissues in the body, and this is driven in large part by the metabolic needs of PRs. Recent studies suggest that disruption of nutrient availability and regulation of cell metabolism may be a unifying mechanism in PR death. Understanding retinal cell metabolism and how it is altered in disease has been identified as a priority area of research. The focus of this review is on the recent advances in the understanding of PR metabolism and how it is critical to reduction-oxidation (redox) balance, the outer retinal metabolic ecosystem, and retinal disease. The importance of these metabolic processes is just beginning to be realized and unraveling the metabolic and redox pathways integral to PR health may identify novel targets for neuroprotective strategies that prevent blindness in the heterogenous group of retinal disorders.

The innate immune system in diabetic retinopathy.

The prevalence of diabetes has been rising steadily in the past half-century, along with the burden of its associated complications, including diabetic retinopathy (DR). DR is currently the most common cause of vision loss in working-age adults in the United States. Historically, DR has been diagnosed and classified clinically based on what is visible by fundoscopy; that is vasculature alterations. However, recent technological advances have confirmed pathology of the neuroretina prior to any detectable vascular changes. These, coupled with molecular studies, and the positive impact of anti-inflammatory therapeutics in DR patients have highlighted the central involvement of the innate immune system. Reminiscent of the systemic impact of diabetes, immune dysregulation has become increasingly identified as a key element of the pathophysiology of DR by interfering with normal homeostatic systems. This review uses the growing body of literature across various model systems to demonstrate the clear involvement of all three pillars of the immune system: immune-competent cells, mediators, and the complement system. It also demonstrates how the relative contribution of each of these requires more extensive analysis, including in human tissues over the continuum of disease progression. Finally, although this review demonstrates how the complex interactions of the immune system pose many more questions than answers, the intimately connected nature of the three pillars of the immune system may also point to possible new targets to reverse or even halt reverse retinopathy.

Calcitonin Receptor Neurons in the Mouse Nucleus Tractus Solitarius Control Energy Balance via the Non-aversive Suppression of Feeding.

To understand hindbrain pathways involved in the control of food intake, we examined roles for calcitonin receptor (CALCR)-containing neurons in the NTS. Ablation of NTS Calcr abrogated the long-term suppression of food intake, but not aversive responses, by CALCR agonists. Similarly, activating CalcrNTS neurons decreased food intake and body weight but (unlike neighboring CckNTS cells) failed to promote aversion, revealing that CalcrNTS neurons mediate a non-aversive suppression of food intake. While both CalcrNTS and CckNTS neurons decreased feeding via projections to the PBN, CckNTS cells activated aversive CGRPPBN cells while CalcrNTS cells activated distinct non-CGRP PBN cells. Hence, CalcrNTS cells suppress feeding via non-aversive, non-CGRP PBN targets. Additionally, silencing CalcrNTS cells blunted food intake suppression by gut peptides and nutrients, increasing food intake and promoting obesity. Hence, CalcrNTS neurons define a hindbrain system that participates in physiological energy balance and suppresses food intake without activating aversive systems.

Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake.

Ambiguity regarding the role of glucose-dependent insulinotropic polypeptide (GIP) in obesity arises from conflicting reports asserting that both GIP receptor (GIPR) agonism and antagonism are effective strategies for inhibiting weight gain. To enable identification and manipulation of Gipr-expressing (Gipr) cells, we created Gipr-Cre knockin mice. As GIPR-agonists have recently been reported to suppress food intake, we aimed to identify central mediators of this effect. Gipr cells were identified in the arcuate, dorsomedial, and paraventricular nuclei of the hypothalamus, as confirmed by RNAscope in mouse and human. Single-cell RNA-seq identified clusters of hypothalamic Gipr cells exhibiting transcriptomic signatures for vascular, glial, and neuronal cells, the latter expressing somatostatin but little pro-opiomelanocortin or agouti-related peptide. Activation of Gq-DREADDs in hypothalamic Gipr cells suppressed food intake in vivo, which was not obviously additive with concomitant GLP1R activation. These data identify hypothalamic GIPR as a target for the regulation of energy balance.

Transcriptional and physiological roles for STAT proteins in leptin action.

OBJECTIVES: Leptin acts via its receptor LepRb on specialized neurons in the brain to modulate food intake, energy expenditure, and body weight. LepRb activates signal transducers and activators of transcription (STATs, including STAT1, STAT3, and STAT5) to control gene expression. METHODS: Because STAT3 is crucial for physiologic leptin action, we used TRAP-seq to examine gene expression in LepRb neurons of mice ablated for Stat3 in LepRb neurons (Stat3LepRbKO mice), revealing the STAT3-dependent transcriptional targets of leptin. To understand roles for STAT proteins in leptin action, we also ablated STAT1 or STAT5 from LepRb neurons and expressed a constitutively-active STAT3 (CASTAT3) in LepRb neurons. RESULTS: While we also found increased Stat1 expression and STAT1-mediated transcription of leptin-regulated genes in Stat3LepRbKO mice, ablating Stat1 in LepRb neurons failed to alter energy balance (even on the Stat3LepRbKO background); ablating Stat5 in LepRb neurons also failed to alter energy balance. Importantly, expression of a constitutively-active STAT3 (CASTAT3) in LepRb neurons decreased food intake and body weight and improved metabolic parameters in leptin-deficient (ob/ob) mice, as well as in wild-type animals. CONCLUSIONS: Thus, STAT3 represents the unique STAT protein required for leptin action and STAT3 suffices to mediate important components of leptin action in the absence of other LepRb signals.

Large-Scale Variability of Inpatient Tacrolimus Therapeutic Drug Monitoring at an Academic Transplant Center: A Retrospective Study.

BACKGROUND: Inpatient tacrolimus therapeutic drug monitoring (TDM) lacks standardized guidelines. In this study, the authors analyzed variability in the preanalytical phase of the inpatient tacrolimus TDM process at their institution. METHODS: Patients receiving tacrolimus (twice-daily formulation) and tacrolimus laboratory analysis were included in the study. Times of tacrolimus administration and laboratory study collection were extracted, and time distribution plots for each step in the inpatient TDM process were generated. RESULTS: Trough levels were drawn appropriately in 25.9% of the cases. Timing between doses was consistent, with 91.9% of the following dose administrations occurring 12 ± 2 hours after the previous dose. Only 38.1% of the drug administrations occurred within 1 hour of laboratory study collection. Tacrolimus-related patient safety events were reported at a rate of 1.9 events per month while incorrect timing of TDM sample collection occurred approximately 200 times per month. Root cause analysis identified a TDM process marked by a lack of communication and coordination of drug administration and TDM sample collection. Extrapolating findings nationwide, we estimate $22 million in laboratory costs wasted annually. CONCLUSIONS: Based on this large single-center study, the authors concluded that the inpatient TDM process is prone to timing errors, thus is financially wasteful, and at its worst harmful to patients due to clinical decisions being made on the basis of unreliable data. Further work is needed on systems solutions to better align the laboratory study collection and drug administration processes.

Defining the Transcriptional Targets of Leptin Reveals a Role for Atf3 in Leptin Action.

Leptin acts via its receptor (LepRb) to modulate gene expression in hypothalamic LepRb-expressing neurons, thereby controlling energy balance and glucose homeostasis. Despite the importance of the control of gene expression in hypothalamic LepRb neurons for leptin action, the transcriptional targets of LepRb signaling have remained undefined because LepRb cells contribute a small fraction to the aggregate transcriptome of the brain regions in which they reside. We thus employed translating ribosome affinity purification followed by RNA sequencing to isolate and analyze mRNA from the hypothalamic LepRb neurons of wild-type or leptin-deficient (Lepob/ob) mice treated with vehicle or exogenous leptin. Although the expression of most of the genes encoding the neuropeptides commonly considered to represent the main targets of leptin action were altered only following chronic leptin deprivation, our analysis revealed other transcripts that were coordinately regulated by leptin under multiple treatment conditions. Among these, acute leptin treatment increased expression of the transcription factor Atf3 in LepRb neurons. Furthermore, ablation of Atf3 from LepRb neurons (Atf3LepRbKO mice) decreased leptin efficacy and promoted positive energy balance in mice. Thus, this analysis revealed the gene targets of leptin action, including Atf3, which represents a cellular mediator of leptin action.