Herpetic esophagitis (HE), primarily caused by the herpes simplex virus (HSV)-1, is most commonly encountered in immunocompromised hosts, although it has been occasionally observed in immunocompetent patients. In the immunocompromised setting, it is typically correlated with human immunodeficiency virus (HIV) infection, malignancy, chemotherapy and radiotherapy, solid organ transplant, as well as the use of systemic corticosteroids and other immunosuppressive agents. We present the case of a 35-year-old patient on hemodialysis due to diabetic nephropathy who, after having received intranasal corticosteroids for three weeks, developed nausea, vomiting, and epigastric pain. Gastroscopy and subsequent biopsy revealed ulcerative esophagitis compatible with herpetic infection. Immunohistochemistry was negative for cytomegalovirus (CMV), while subsequent quantitative polymerase chain reaction (PCR) testing was positive for HSV-1, establishing the diagnosis of HSV esophagitis. After a 14-day course of valacyclovir, complete relief of symptoms was achieved. Herpetic esophagitis may occur in immunocompetent persons, whereas intranasal corticosteroids cannot be ruled out as potential contributors. Symptoms such as odynophagia, dysphagia, and fever in that setting warrant further investigation.

Keratitis, characterized by inflammation of the cornea, presents a diagnostic challenge, particularly when the etiology remains elusive. Here, we report a perplexing case of keratitis in a 35-year-old patient with no identifiable risk factors or predisposing conditions. Despite the initial uncertainty, empirical treatment with antiviral medications led to a rapid resolution of symptoms and improvement in corneal health. This case underscores the importance of considering viral etiologies even in cases with atypical presentations and highlights the potential efficacy of antiviral therapy in such scenarios. Further investigation is needed to understand the underlying causes and improve treatment approaches for similar cases of unexplained keratitis.

Herpes simplex virus-1 (HSV-1) is common and can cause significant disease in humans. Unfortunately, efforts to develop effective vaccines against HSV-1 have so far failed. A detailed understanding of how the virus infects its host and how the host mounts potent immune responses against the virus may inform new vaccine approaches. Here, using a zosteriform mouse model, we examined how the HSV-1 gene UL56 affects the ability of the virus to cause morbidity and generate protective immunity. A UL56 deletion mutant, ΔUL56, was derived from the wild-type HSV-1 strain SC16, alongside a revertant strain in which UL56 was reintroduced in ΔUL56. In vitro, the three virus strains replicated in a similar manner; however, in vivo, only the wild type and the revertant strains caused shingles-like skin lesions and death. Mice previously infected with ΔUL56 became resistant to a lethal challenge with the wild-type SC16. The protective immunity induced by ΔUL56 was independent of IL-1, IL-33, and IL-36 signaling through IL-1RAP. Both skin and intramuscular ΔUL56 inoculation generated protective immunity against a lethal SC16 challenge. After 6 months, female mice remained resistant to infection, while male mice exhibited signs of declining protection. Our data demonstrate that UL56 is important for the ability of HSV-1 to spread within the infected host and that a ∆UL56 strain elicits an effective immune response against HSV-1 despite this loss of virulence. These findings may guide further HSV-1 vaccine development.

Herpes simplex viruses (HSV) are common human pathogens with a combined global seroprevalence of 90% in the adult population. HSV-1 causes orofacial herpes but can cause severe diseases, such as the potentially fatal herpes encephalitis and herpes keratitis, a prevalent cause of infectious blindness. The hallmark of HSV is lifelong latent infections and viral reactivations, leading to recurrent lesions or asymptomatic shedding. HSV-1 and HSV-2 can cause recurrent, painful, and socially limiting genital lesions, which predispose to human immunodeficiency virus infections, and can lead to neonatal herpes infections, a life-threatening condition for the newborn. Despite massive efforts, there is no vaccine against HSV, as both viruses share the capability to evade the antiviral defenses of human and to establish lifelong latency. Recurrent and primary HSV infections are treated with nucleoside analogs, but the treatments do not completely eliminate viral shedding and transmission. Drug-resistant HSV strains can emerge in relation to long-term prophylactic treatment. Such strains are likely to be resistant to other chemotherapies, justifying the development of novel antiviral treatments. The importance of developing new therapies against HSV has been recognized by the World Health Organization. In this review, we discuss the current approaches for developing novel antiviral therapies against HSV, such as small molecule inhibitors, biopharmaceuticals, natural products, gene editing, and oligonucleotide-based therapies. These approaches may have potential in the future to answer the unmet medical need. Furthermore, novel approaches are presented for potential eradication of latent HSV.

Chronic kidney disease (CKD) is a widespread condition with considerable health and economic impacts globally. However, existing methodologies for serum creatinine assessment often involve prolonged wait times and sophisticated equipment, such as spectrometers, hindering real-time diagnosis and care. Innovative solutions like point-of-care (POC) devices are emerging to address these challenges. In this context, there is a recognized need for remote, regular, automated, and low-cost analysis of serum creatinine levels, given its role as a critical parameter for CKD diagnosis and management. This study introduces a miniaturized system with integrated heater elements designed for precise serum creatinine measurement. The system operates based on the Jaffe method and accurate serum creatinine measurement within a microreservoir chip. Smartphone-based image processing using the hue-saturation-value (HSV) color space was applied to captured images of microreservoirs. The creatinine analyses were conducted in serum with a limit of detection of ~ 0.4 mg/dL and limit of quantification of ~ 1.3 mg/dL. Smartphone-based image processing employing the HSV color space outperformed spectrometric analysis for creatinine measurement conducted in serum. This pioneering technology and smartphone-based processing offer the potential for decentralized renal function testing, which could significantly contribute to improved patient care. The miniaturized system offers a low-cost alternative ($87 per device), potentially reducing healthcare expenditures (~ $0.5 per test) associated with CKD diagnosis and management. This innovation could greatly improve access to diagnosis and monitoring of CKD, especially in regions where access to sophisticated laboratory equipment is limited.

UNASSIGNED: Head and neck cancer (HNC) is a complex disease, and multiple risk factors can lead to its progression. Observational studies indicated that herpes simplex virus (HSV) may be correlated with the risk of HNC. However, the causal effects and direction between them were still unclear.
UNASSIGNED: This study utilized a Mendelian randomization (MR) approach for causality assessment between HSV infection and Head and neck cancer based on the latest public health data and Genome-Wide Association Study (GWAS) data. The causal effects were estimated using IVW, weighted median, and MR-Egger. A reverse MR analysis was subsequently performed. Cochrans Q test, MR-Egger intercept test, leave one out analysis, and the funnel plot were all used in sensitivity analyses.
UNASSIGNED: Genetically predicted higher level of HSV-1 IgG was causally related to HNC (OR=1.0019, 95%CI=1.0003-1.0036, p=0.0186, IVW) and oral and oropharyngeal cancer (OR=1.0018, 95%CI=1.0004-1.0033, p=0.0105, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and HNC. However, HSV-2 infection was not causally related to HNC data and oropharyngeal cancer data. Sensitivity analysis was performed and revealed no heterogeneity and horizontal pleiotropy.
UNASSIGNED: Collectively, a significant association was noted between HSV infection and increased risk of HNC, providing valuable insights into the etiology of this malignancy. Further in-depth study is needed to validate these findings and elucidate the underpinning mechanisms.

Color-blind is a generic disability whereby the affected individuals are not given the opportunity to benefit from the various functions provided by color that would impact humans physically and psychologically. Although this disability is not fatal, it brought plenty of turbulence in the affected individuals\' daily activities. This paper aims to develop a system for recognizing and detecting colors of clothes in images, improve accuracy by using advanced algorithms to handle lighting variations, and provide color matching recommendations to assist color-blind individuals in making informed choices when purchasing shirts. The proposed methodology for color recognition involves:•retrieving the RGB values of a given point from the input image and converting them into HSV values.•creating web application integrated with a machine learning model to classify and predict the corresponding color based on the HSV values.•predicting the color name with suggestions of matching colors will be displayed on the interface.

The multifunctional tegument protein pUL21 of HSV-2 is phosphorylated in infected cells. We have identified two residues in the unstructured linker region of pUL21, serine 251 and serine 253, as phosphorylation sites. Both phosphorylation sites are absent in HSV-1 pUL21, which likely explains why phosphorylated pUL21 was not detected in cells infected with HSV-1. Cells infected with HSV-2 strain 186 viruses deficient in pUL21 phosphorylation exhibited reductions in both cell-cell spread of virus infection and virus replication. Defects in secondary envelopment of cytoplasmic nucleocapsids were also observed in cells infected with viruses deficient in pUL21 phosphorylation as well as in cells infected with multiple strains of HSV-2 and HSV-1 deleted for pUL21. These results confirm a role for HSV pUL21 in the secondary envelopment of cytoplasmic nucleocapsids and indicate that phosphorylation of HSV-2 pUL21 is required for this activity. Phosphorylation of pUL21 was substantially reduced in cells infected with HSV-2 strain 186 mutants lacking the viral serine/threonine kinase pUL13, indicating a requirement for pUL13 in pUL21 phosphorylation.
OBJECTIVE: It is well known that post-translational modification of proteins by phosphorylation can regulate protein function. Here, we determined that phosphorylation of the multifunctional HSV-2 tegument protein pUL21 requires the viral serine/threonine kinase pUL13. In addition, we identified serine residues within HSV-2 pUL21 that can be phosphorylated. Phenotypic analysis of mutant HSV-2 strains with deficiencies in pUL21 phosphorylation revealed reductions in both cell-cell spread of virus infection and virus replication. Deficiencies in pUL21 phosphorylation also compromised the secondary envelopment of cytoplasmic nucleocapsids, a critical final step in the maturation of all herpes virions. Unlike HSV-2 pUL21, phosphorylation of HSV-1 pUL21 was not detected. This fundamental difference between HSV-2 and HSV-1 may underlie our previous observations that the requirements for pUL21 differ between HSV species.

BACKGROUND: Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥ 5 cells/µL), to inform timely diagnosis and management of encephalitis.
METHODS: This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis.
RESULTS: Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-NMDAR encephalitis (37/59, 62.7%). Notably, the group without pleocytosis was comprised of similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; p>0.05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had absent pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs. 71.1% in patients with pleocytosis, p<0.001). Despite pleocytosis being associated with some measures of clinical severity at admission such as a Full Outline of UnResponsiveness (FOUR) score ≤14, it was not associated with mortality or prolonged hospitalization.
CONCLUSIONS: CSF pleocytosis is an important criterion for encephalitis diagnosis, but 25.3% of patients with all-cause encephalitis and 23.7% of those with HSV-1 encephalitis exhibit absence of pleocytosis on initial LP. Acyclovir initiation should not be delayed in the absence of pleocytosis in patients with suspected encephalitis.

OBJECTIVE: As herpes simplex virus (HSV) in infancy is not a mandatory notifiable condition in Australia, completeness of ascertainment by the Australian Paediatric Surveillance Unit (APSU) has been difficult to evaluate to date. We evaluated case capture in Queensland (QLD) and Western Australia (WA) using statewide laboratory and clinical data and complementary surveillance data collected via the APSU.
METHODS: HSV polymerase chain reaction positive results in infants (0-3 months) from 2007 to 2017 were obtained from statewide public pathology providers in QLD and WA. Clinical data were extracted from patient records and compared to APSU reported cases.
RESULTS: A total of 94 cases of HSV disease in infancy (70 QLD; 24 WA) were identified from laboratory data sets, compared to 36 cases (26 QLD; 10 WA) reported to the APSU. In total there was 102 unique cases identified; 28 cases were common to both data sets (seven skin eye mouth (SEM) disease, 13 central nervous system (CNS) disease and eight disseminated disease). Active surveillance captured 35% (36/102) of cases overall including 74% (14/19) of CNS, 71% (10/14) of disseminated and 17% (12/69) of SEM disease cases, respectively. Surveillance reported cases had a higher case-fatality rate compared to those not reported (14% vs. 3%, P = 0.038). Neurological sequelae at discharge were comparable between the groups.
CONCLUSIONS: Active surveillance captures one third of hospitalised HSV cases in QLD and WA, including the majority with severe disease. However, morbidity and mortality remain high. Future studies on HSV will rely on observational studies. Enhanced case ascertainment through combined laboratory and surveillance data is essential for better understanding and improving outcomes.