Challenges in Managing Treatment-Resistant Mpox Complicated by Severe Superinfection.

Though typically self-limiting, severe mpox infections have been treated with antiviral medications, most notably tecovirimat. Various reports exist of mpox progression despite tecovirimat treatment. Treatment resistance can be due to acquired mpox strain mutations, most often occurring in an immunocompromised host. We present the case of a male with AIDS who developed disseminated treatment-resistant mpox infection complicated by superimposed bacterial and fungal infections. His orthopoxvirus polymerase chain reaction result remained positive despite treatment with 4 weeks of oral tecovirimat and 3 doses of intravenous cidofovir. Poor response to antiviral therapy was likely due to his underlying immunocompromised state; however, strain resistance cannot be ruled out given that the patient had started but not completed a 14-day course of tecovirimat 8 months prior, at the time of initial mpox diagnosis. Patients with mpox who are immunocompromised may require extended and additional treatment beyond the standard 14 days of tecovirimat, such as cidofovir, brincidofovir, or intravenous vaccina immune globulin.

Diffuse Large B-cell Lymphoma of the Orbit With Intracranial Extension: A Rare Entity.

Primary diffuse large B-cell lymphoma of the orbit is a rare diagnosis that accounts for less than 1% of all non-Hodgkin's lymphoma (NHL) cases. We present here the case of a middle-aged woman with a past medical history of intellectual delay and hypothyroidism who presented with a large diffusely infiltrating mass of the left orbit. A biopsy of the lesion during the patient's hospitalization confirmed a diagnosis of diffuse, large B-cell lymphoma. Due to extensive local invasion, she was deemed a poor surgical candidate. While inpatient, she was started on systemic chemotherapy and discharged with close follow-up planned with the oncologic and surgical teams.

The Double-Edged Sword: Naloxone-Induced Noncardiogenic Pulmonary Edema.

Naloxone-induced noncardiogenic pulmonary edema (NCPE) is a scarcely reported side effect that can occur after naloxone administration. We present a case of a 46-year-old male who presented to the emergency department for further management of an opioid overdose, who developed acute hypoxic respiratory failure after several doses of naloxone. The rapid deterioration of the patient's respiratory status required increased supplemental oxygen, with plane film radiography suggesting diffuse pulmonary edema. This case emphasizes the importance of understanding the significant side effects of a lifesaving drug and the implications they carry now that naloxone is available without prescription.

Cardiac Sarcoidosis: A Case Report on the Role of Cardiac Computed Tomography (CT) in the Evaluation of Advanced Atrioventricular Block.

Cardiac sarcoidosis is a rare autoimmune condition that is characterized by the presence of non-caseating granulomas in the cardiac tissue. We present the case of a 31-year-old male with no significant past medical history who presented with palpitations and lightheadedness during exertion for two to three months and was found to have complete heart block on his 12-lead electrocardiogram. A cardiac CT was obtained to rule out an ischemic event, but it indicated findings suggestive of pulmonary sarcoidosis. The CT findings helped tremendously with narrowing down the differential diagnosis and providing efficient diagnostic and therapeutic management.

A Stroke of Luck: Central Diabetes Insipidus Unmasked by a Heat Stroke.

Diabetes insipidus is a rarely encountered cause of hypernatremia, often presenting a diagnostic and therapeutic dilemma for the encountering physician. Patients are often asymptomatic for a number of years due to compensation of their polyuria with polydipsia, but may have dramatic presentations in situations where they lose access to hydration. Our case is of a 62-year-old woman who was found unconscious with signs and symptoms of a heat stroke, and later was found to have resistant hypernatremia that persisted despite extensive free water supplementation. She had dilute polyuria throughout her hospital course, eventually warranting testing for diabetes insipidus with a vasopressin challenge test. She responded well to therapy with intranasal desmopressin and currently remains asymptomatic. Because our patient was reported to have polyuria and polydipsia for a number of years presumed to be due to underlying diabetes mellitus, it is possible that she had pre-existing central diabetes insipidus that was exacerbated by the lack of access to free water while she was in her intubated and sedated state. Alternatively, she may have also developed new-onset diabetes insipidus due to severe hyperthermia. This case serves to highlight a dramatic presentation of diabetes insipidus, and the importance of careful consideration of its diagnosis in patients with persistent dilute polyuria despite signs of intravascular volume depletion.

Hypercalcaemia secondary to acute rhinovirus infection.

Hypercalcaemia-induced rhinovirus has only been reported in a single study in children. Here, we report a case of hypercalcaemia in an adult who tested positive for rhinovirus. This patient underwent an extensive evaluation of hypercalcaemia, and it was found to be mediated by an increase in 1,25 hydroxy-vitamin D that could not be attributed to a cause. Their hypercalcaemia responded to standard treatment with intravascular expansion, bisphosphonates and calcitonin. Serum 1,25 OH vitamin D levels returned to normal with recovery from rhinovirus infection.

A Breathtaking Hernia: A Giant Hiatal Hernia Masquerading as Poorly Controlled Asthma.

A 93-year-old female presented with persistent shortness of breath and wheezing since the consumption of a meal. Her past medical history is significant for a clinical diagnosis of asthma at the age of 88 years, without pulmonary function testing, complicated by several prior visits to the emergency department (ED) for recurrent exacerbations. Multiple bronchodilators in the ED provided only minimal improvement in her symptoms. Chest imaging eventually revealed a giant, fluid-filled hiatal hernia exhibiting a compressive effect on the posterior aspect of the left atrium. The etiology of the patient's airway bronchoconstriction was likely multifactorial. We hypothesize that the extrinsic, dynamic compression of the bronchial tree by the peristaltic motion of the hiatal hernia, microaspiration from gastroesophageal reflux, and peribronchial edema from left atrial compression accounted for our patient's unique presentation. An outpatient methacholine challenge test eventually excluded bronchial asthma. Although she was considered a poor surgical candidate, she has had no further recurrences of her symptoms with counseling on conservative lifestyle changes. This case serves to highlight the heterogeneity in presentations of hiatal hernias, particularly in elderly females. Furthermore, it remains prudent to maintain a broad differential for wheezing, as evidenced by our patient who was previously managed for a number of years as poorly controlled asthma.

A Case of Multiple Calcific Embolic Strokes in a Patient With a Porcelain Left Atrium.

Mitral annular calcification (MAC) commonly manifests as an incidental, asymptomatic finding that is associated with several cardiovascular risk factors, atherosclerosis, cardiovascular death, and all-cause mortality. Very rarely, patients with severe MAC can have extensive dystrophic calcification extending into the left atrial wall, termed porcelain left atrium. In this case report, we describe a patient who experienced multiple calcific acute embolic strokes in the setting of severe mitral annular calcification and porcelain left atrium. Our patient presented with multiple, small bilateral acute infarcts scattered throughout the cerebrum and cerebellum confirmed on magnetic resonance imaging (MRI). He was placed on continuous telemetry and underwent multimodal imaging with transthoracic and transesophageal echocardiography, carotid neck ultrasound (US), head and neck computed tomography angiogram (CTA), and cardiac MRI. There were no arrhythmic events detected on telemetry, and all imaging excluded left ventricular thrombi, aortic atheroma, carotid artery stenosis, intracardiac shunting, or large vessel stenosis. Noted on imaging, however, was severe mitral annular calcification with numerous, highly mobile calcific extensions and densely calcified plaque along the posterior left atrial wall, presumed to be the source of this patient's embolic stroke. Cardiac catheterization was significant for severe three-vessel disease requiring coronary artery bypass grafting, and our patient was subsequently discharged to outpatient follow-up on event monitoring and aspirin monotherapy. This case serves to highlight a previously unreported complication of calcific embolic stroke in severe MAC and porcelain left atrium, and highlight the need for further randomized controlled trials to determine the optimum management of these cases.

The complete chloroplast genome of the monotypic genus of Bulleyia Schltr. (Orchidaceae).

Bulleyia Schltr. is monotypic and represented only by Bulleyia yunnanensis Schltr., native to the Yunnan of China, Bhutan, and northeast India. Here, we report the complete chloroplast (cp) genome sequence and the cp genome features of B. yunnanensis. The cp genome sequence of B. yunnanensis was 159,581 bp in length and presented a typical quadripartite structure consisting of one large single-copy region (LSC, 87,563 bp), one small single-copy region (SSC, 18,714 bp), and two inverted repeat regions (IR, 26,652 bp). Besides, the cp genome encoded 132 genes, including 113 unique genes (79 protein-coding genes, 30 tRNA genes, and four rRNA genes). The phylogenetic analysis suggested that B. yunnanensis be closely related to Pholidota in tribe Arethuseae.

The complete chloroplast genome of Coelogyne barbata (Orchidaceae), a rare and ornamental orchid.

The genus of Coelogyne Lindl. comprised about 200 species while its generic relationship has been uncertain. The whole chloroplast genome of C. barbata was reported in order to provide new data on the molecular phylogeny of Coelogyne. The cp genome of C. barbata was 1,600,93 bp in total length, including a pair of inverted repeat regions (IR, 26,710 bp), one large single-copy region (LSC, 87,868 bp), and one small single-copy region (SSC, 188,05 bp). The complete chloroplast DNA encoded 132 genes, containing 86 protein-coding genes, 38 tRNA genes, and eight rRNA genes. Phylogenetic analysis showed that C. barbata was related to Pholidota imbricata.

Regulatory effects of chicken TRIM25 on the replication of ALV-A and the MDA5-mediated type I interferon response.

This study focuses on the immunoregulatory effects of chicken TRIM25 on the replication of subgroup A of avian leukosis virus (ALV-A) and the MDA5-mediated type I interferon response. The ALV-A-SDAU09C1 strain was inoculated into DF1 cells and 1-day-old SPF chickens, and the expression of TRIM25 was detected at different time points after inoculation. A recombinant overexpression plasmid containing the chicken TRIM25 gene (TRIM25-GFP) was constructed and transfected into DF1 cells to analyse the effects of the overexpression of chicken TRIM25 on the replication of ALV-A and the expression of MDA5, MAVS and IFN-ß. A small interfering RNA targeting chicken TRIM25 (TRIM25-siRNA) was prepared and transfected into DF1 cells to assess the effects of the knockdown of chicken TRIM25 on the replication of ALV-A and the expression of MDA5, MAVS and IFN-ß. The results showed that chicken TRIM25 was significantly upregulated at all time points both in ALV-A-infected cells and in ALV-A-infected chickens. Overexpression of chicken TRIM25 in DF1 cells dramatically decreased the antigenic titres of ALV-A in the cell supernatant and upregulated the relative expression of MDA5, MAVS and IFN-ß induced by ALV-A or by poly(I:C); in contrast, knockdown of chicken TRIM25 significantly increased the antigenic titres of ALV-A and downregulated the relative expression of MDA5, MAVS and IFN-ß. It can be concluded that chicken TRIM25 can inhibit the replication of ALV-A and upregulate the MDA5 receptor-mediated type I interferon response in chickens. This study can help improve the understanding of the antiviral activities of chicken TRIM25 and enrich the knowledge of antiviral responses in chickens.

Preparation of a new monoclonal antibody against subgroup A of avian leukosis virus and identifying its antigenic epitope.

This study focuses on preparing the monoclonal antibody (MAb) against subgroup A of avian leukosis virus (ALV-A) and identifying its antigenic epitope. The ALV-A gp85 gene with a size of 1005bp was amplified and expressed into a recombinant protein with a size of 46KD in E.coli. The products expressed after purification were inoculated into BALB/c mice for preparing antibody-secreting splenic lymphocytes and further obtaining hybridoma cells. Finally, one new hybridoma cell (A18GH) secreting MAb against ALV-A was screened, and the MAb was able to detect ALV-A/K strains in an indirect immunofluorescence assay (IFA), but not ALV-B/J strains. A total of 14 overlapping truncated ALV-A gp85 protein segments were expressed and eight peptides containing different antigenic amino acids were artificially synthesized for analyzing the antigenic epitope of the MAb using a western blot or an ELISA, and the results indicate that the antigenic epitope consists of seven amino acids within the 146-ATRFLLR -152 region of the ALV-A gp85 protein. A biological information analysis shows that the antigenic epitope has a high antigenic index and develops a curved linear spatial structure. Further, its 7 amino acids are completely within the 17 representative ALV-A strains, 4 are within the 11 ALV-K strains, and fewer are within the ALV-B/J/E strains. This study will significantly assist in a further understanding of the protein structure and function of ALV-A, and in the establishment of specific ALV-A detection methods.

Advantages of Chinese Medicine for Patients with Acquired Immunodeficiency Syndrome in Rural Central China.

OBJECTIVE: To analyze the effect of Chinese medicine (CM) on mortality and quality of life (QOL) of acquired immunodefificiency syndrome (AIDS) patients treated with combined antiretroviral therapy (cART). METHODS: A random sample of AIDS patients enrolled in the National Chinese Medicine Treatment Trial Program (NCMTP) that met the inclusion criteria was included in this study. NCMTP patients were included as the CM+cART group, and those not in the NCMTP were included as the cART group. Survival from September 2004 to September 2012 was analyzed by retrospective cohort study. QOL was analyzed by cross-sectional study. RESULTS: The retrospective cohort study included 528 AIDS patients, 322 in the CM+cART group and 206 in the cART group. After 8 years, the mortality in the CM+cART group was 3.3/100 person-years, which was lower than the cART group of 5.3/100 person-years (P<0.05). The hazard ratio (HR) for mortality in the cART group was 1.6 times that of the CM+cART group by Cox proportional hazard model analysis. After controlling for gender, age, marital status, education, and CD4+ T-cell count, the HR was 1.9 times higher in the cART group compared with the CM+cART group (P<0.05). The cross-sectional study investigated 275 AIDS patients. The mean scores of all QOL domains except spirituality/personal beliefs were higher in the CM+cART group than in the cART group (P<0.05). CONCLUSIONS: For AIDS patients, CM could help to prolong life, decrease mortality, and improve QOL. However, there were limitations in the study, so prospective studies should be carried out to confifirm our primary results.

Governor vessel moxibustion: Ancient Chinese medical technology with new vitality.

Moxibustion is an ancient therapeutic technique used in Chinese medicine. Governor Vessel moxibustion (GVM) was developed from long snake moxibustion, a popular technique used in China's Jiangsu and Zhejiang Provinces, and is significantly more effective than general moxibustion. We aimed to review GVM, including its theoretical basis, choices of moxibustion points and materials, operation procedures, clinical applications, and contraindications. This information could increase the appropriate use of GVM and support further in-depth research.

Naf1 Regulates HIV-1 Latency by Suppressing Viral Promoter-Driven Gene Expression in Primary CD4+ T Cells.

HIV-1 latency is characterized by reversible silencing of viral transcription driven by the long terminal repeat (LTR) promoter of HIV-1. Cellular and viral factors regulating LTR activity contribute to HIV-1 latency, and certain repressive cellular factors modulate viral transcription silencing. Nef-associated factor 1 (Naf1) is a host nucleocytoplasmic shuttling protein that regulates multiple cellular signaling pathways and HIV-1 production. We recently reported that nuclear Naf1 promoted nuclear export of unspliced HIV-1 gag mRNA, leading to increased Gag production. Here we demonstrate new functions of Naf1 in regulating HIV-1 persistence. We found that Naf1 contributes to the maintenance of HIV-1 latency by inhibiting LTR-driven HIV-1 gene transcription in a nuclear factor kappa B-dependent manner. Interestingly, Naf1 knockdown significantly enhanced viral reactivation in both latently HIV-1-infected Jurkat T cells and primary central memory CD4+ T cells. Furthermore, Naf1 knockdown in resting CD4+ T cells from HIV-1-infected individuals treated with antiretroviral therapy significantly increased viral reactivation upon T-cell activation, suggesting an important role of Naf1 in modulating HIV-1 latency in vivo Our findings provide new insights for a better understanding of HIV-1 latency and suggest that inhibition of Naf1 activity to activate latently HIV-1-infected cells may be a potential therapeutic strategy. IMPORTANCE: HIV-1 latency is characterized mainly by a reversible silencing of LTR promoter-driven transcription of an integrated provirus. Cellular and viral proteins regulating LTR activity contribute to the modulation of HIV-1 latency. In this study, we found that the host protein Naf1 inhibited HIV-1 LTR-driven transcription of HIV genes and contributed to the maintenance of HIV-1 latency. Our findings provide new insights into the effects of host modulation on HIV-1 latency, which may lead to a potential therapeutic strategy for HIV persistence by targeting the Naf1 protein.

The variances of Sp1 and NF-κB elements correlate with the greater capacity of Chinese HIV-1 B'-LTR for driving gene expression.

The 5' end of HIV-1 long terminal repeat (LTR) serves as a promoter that plays an essential role in driving viral gene transcription. Manipulation of HIV-1 LTR provides a potential therapeutic strategy for suppressing viral gene expression or excising integrated provirus. Subtype-specific genetic diversity in the LTR region has been observed. The minor variance of LTR, particularly in the transcription factor binding sites, can have a profound impact on its activity. However, the LTR profiles from major endemic Chinese subtypes are not well characterized. Here, by characterizing the sequences and functions of LTRs from endemic Chinese HIV-1 subtypes, we showed that nucleotide variances of Sp1 core promoter and NF-κB element are associated with varied LTR capacity for driving viral gene transcription. The greater responsiveness of Chinese HIV-1 B'-LTR for driving viral gene transcription upon stimulation is associated with an increased level of viral reactivation. Moreover, we demonstrated that the introduction of CRISPR/dead Cas9 targeting Sp1 or NF-κB element suppressed viral gene expression. Taken together, our study characterized LTRs from endemic HIV-1 subtypes in China and suggests a potential target for the suppression of viral gene expression and a novel strategy that facilitates the accomplishment of a functional cure.

Gibberellins regulate the stem elongation rate without affecting the mature plant height of a quick development mutant of winter wheat (Triticum aestivum L.).

Gibberellin (GA) is essential for determining plant height. Alteration of GA content or GA signaling results in a dwarf or slender phenotype. Here, we characterized a novel wheat mutant, quick development (qd), in which GA regulates stem elongation but does not affect mature plant height. qd and wild-type plants did not exhibit phenotypic differences at the seedling stage. From jointing to heading stage, qd plants were taller than wild-type plants due to elongated cells. However, wild-type and qd plants were the same height at heading. Unlike wild-type plants, qd plants were sensitive to exogenous GA due to mutation of Rht-B1. With continuous GA stimulation, qd seedlings and adult plants were taller than wild-type. Thus, the GA content of qd plants might differ from that of wild-type during the growth process. Analysis of GA biosynthetic gene expression verified this hypothesis and showed that TaKAO, which is involved in catalyzing the early steps of GA biosynthesis, was differentially expressed in qd plants compared with wild-type. The bioactive GA associated gene TaGA20ox was downregulated in qd plants during the late growth stages. Measurements of endogenous GA content were consistent with the gene-expression analysis results. Consistent with the GA content variation, the first three basal internodes were longer and the last two internodes were shorter in qd than in wild-type plants. The qd mutant might be useful in dissecting the mechanism by which GA regulates stem-growing process, and it may be serve as a GA responsive semi-dwarf germplasm in breeding programs.