Antibiotic Sensitivity and Nasal Microbiome in Patients with Acute Bacterial Rhinosinusitis.

OBJECTIVES: Acute rhinosinusitis (ARS) is a common upper respiratory tract infection that is mostly of viral origin. However, little is known about the nasal microbiome profile at presentation and the changes caused by antibiotics in acute bacterial rhinosinusitis (ABRS). METHODS: This was a prospective single-center study. Overall, 43 ARS patients were screened and were assessed with the symptom questionnaires, nasal endoscopy, and Water's view. Five healthy subjects were recruited as controls. Middle meatal mucus samples were obtained using a cotton swab (for bacterial culture and antimicrobial susceptibility testing) and the suction technique (for 16S rRNA sequencing). After 1 week of antibiotic use (amoxicillin with clavulanic acid), we enrolled 13 patients with ABRS with positive isolates and middle meatal samples for 16S rRNA sequencing were obtained again. RESULTS: Overall, we demonstrated a significantly lower abundance of the Lactobacillaceae family in ABRS patients than in healthy controls. Resistant ABRS had different characteristics of middle meatal microbiomes when compared to sensitive ABRS as follows: (1) lower proportion of lactic acid bacteria, (2) increased pathogens such as Rhodococcus sp., Massila sp., Acinetobacter sp., and H. influenza, and (3) increased beta diversity. However, no remarkable changes were observed in the middle meatal microbiome after antibiotic use. CONCLUSION: We showed the roles of Lactobacillaceae in ABRS, and Acinetobacter and Massilia in case of amoxicillin resistance. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1081-1088, 2024.

Efficacy of skin rejuvenation with a fractional 1927-nm thulium laser alone or combined with a chemical peel: a controlled histopathological preliminary study in a mouse model.

Many patients demand minimally invasive treatments for skin rejuvenation, such as nonablative laser and superficial chemical peels. Combination therapy yet has not been studied histopathologically. The purpose of this study is to assess the histopathological efficacy of a 1927-nm thulium laser-assisted salicylic acid (SA) peel in skin rejuvenation. A six-segment table was drawn on the shaved back of C57BL/6 mouse. All segments were irradiated with the thulium laser-different tips and passes were used for specific segments. A 30% SA peel was then applied to the right-hand segments. After treatment, the skin samples were collected from each segment and examined for dermal thickness, collagen density, and melanin content. Greater thickness was seen in the combination therapy group compared with the laser alone group and in those segments receiving more passes with larger beam-sized tip. Collagen density increased in all treated skin segments, irrespective of the group. No adverse events were noted in the treated areas. The sample size was small and mouse skin has histological differences with human skin. The combination of a thulium laser and 30% SA peel has a synergistic effect on dermal thickness, so that can be suggested as a novel skin rejuvenation technique.

Sudden Hearing Loss and Vertigo With Silent Pontine Infarction: A Case Report.

Most cases of sudden sensorineural hearing loss (SSNHL) occur without a specific identifiable cause, although vascular factors may serve as potential etiological contributors. Silent infarction refers to ischemic changes observed on imaging studies without accompanying clinical symptoms; however, this condition is clinically significant owing to the increased risk of future stroke. We report a case of left-sided SSNHL accompanied by dizziness in a 62-year-old male patient who was diagnosed with left pontine infarction without any other neurological symptoms. The cochlea and pons receive blood supply from the anterior inferior cerebellar artery; the cochlea lacks collateral vessels and is therefore susceptible to fluctuations in blood flow. This case report provides evidence to support the vascular hypothesis as the etiology underlying SSNHL.

A Pilot Split-Neck Case Study to Compare the Efficacy of the Long-Pulsed 755 nm Laser and the 532 nm Picosecond Laser for Acrochordon Removal.

Cutaneous papillomas or acrochorda usually appear after the 4th decade of life in areas with skin folds. Conventional methods of removal are associated with bleeding problems, pain and prolonged sequelae. Thus, acrochorda removal with lasers has gained attention. In this study, we compared the efficacy of two popular laser types with different wavelengths and pulse widths for removal of skin tags. A 60-year-old Korean male noticed skin tags on his neck bilaterally. All tags were treated in a single session, on one side with a picosecond (ps)-domain 532 nm Nd:YAG laser and on the contralateral side with a long-pulsed (LP) 755 nm alexandrite laser. The endpoint for the ps-532 laser was immediate whitening, while that for the LP and quasi-LP (QLP) 755 lasers were visible changes on the surface of the lesion. Antibiotic ointment was applied, dressing was done and clinical photographs were taken. Both lasers effectively removed the skin tags at all settings in a single session without bleeding and with minimal discomfort. Crust formation occurred on both sides with natural shedding within 1 to 2 weeks. Transient erythema lasted longer in the tags treated with the ps-532 laser. At the 5th month of follow-up, residual lesions were detected on the field treated with the ps-532 laser. No persistent side effects such as scarring or postinflammatory hyperpigmentation (PIH) were observed. In conclusion, both the ps-532 nm Nd:YAG and the 755 nm alexandrite lasers ensured safe and effective removal of skin tags in a single session without adverse sequelae.

Incidence and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy.

PURPOSE: The incidence and risk factors for hypoparathyroidism after total thyroidectomy is well-known. However, the characteristics of hypoparathyroidism and hypocalcemia after hemithyroidectomy have not been investigated well. In this study, we aimed to evaluate the incidence, characteristics, and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy. METHOD: We retrospectively analyzed the medical data of 321 patients who underwent hemithyroidectomy, with or without central neck dissection, from January 2012 to April 2019. We analyzed the serum intact parathyroid hormone (iPTH), calcium, and ionized calcium (iCa) levels serially (preoperatively and postoperatively on the operation day; days 1 and 3; and months 1, 3, 6, and 12) and evaluated risk factors for postoperative hypoparathyroidism and hypocalcemia. RESULTS: The mean iPTH and calcium levels decreased significantly after hemithyroidectomy on the operation day and postoperative days 1 and 3, and returned to the preoperative level at the postoperative 1-month follow-up. The mean iCa level decreased significantly on the operation day and postoperative day 1. Transient hypoparathyroidism and transient hypocalcemia occurred in 16 (5%) and 250 (78%) participants, and they recovered to normal levels postoperatively by 1 month. Eight (2.5%) patients had mild symptoms of hypocalcemia necessitating oral calcium supplementation. No permanent hypoparathyroidism or hypocalcemia was observed. Preoperatively low serum iPTH and calcium levels were associated with transient hypoparathyroidism and hypocalcemia after hemithyroidectomy. CONCLUSION: Approximately 5% and 2.5% of participants showed transient hypoparathyroidism and mild symptomatic hypocalcemia after hemithyroidectomy. The risk factors for transient hypoparathyroidism and hypocalcemia include preoperative low serum iPTH and calcium levels.

A Case of Malignant Transformation of Solitary Recurrent Cylindroma on Scalp.

A 78-year-old male presented with an asymptomatic pinkish multi-nodular mass on his frontal scalp. The lesion had recurred twice after incomplete surgical excision. Initial punch biopsy was diagnosed with cylindroma. He revisited after one year with exophytic enlargement of the mass, and two staged Mohs micrographic surgery identified well-differentiated malignant cylindroma. Histopathology in the lower dermis and periosteal layer showed atypical cells with mitosis and hyperchromatic nucleoli with increased Ki-67 index of 10% to 30%. The postoperative wound was successfully treated with negative wound pressure therapy (NPWT) and secondary intentional healing. We report this case showing malignant transformation of solitary cylindroma, and good result for secondary intention healing using NPWT for postoperative defect.

Efficacy and safety of intense pulsed light using a dual-band filter for the treatment of facial acne vulgaris.

Intense pulsed light (IPL) devices have been used in acne treatment in combination with conventional topical and oral medications. This study aimed to evaluate the efficacy and safety of IPL treatment using a dual-band filter (400-600 nm and 800-1200 nm) in facial acne vulgaris treatment. Twenty-three acne vulgaris patients were enrolled in this study. The patients were treated on both sides of the face. The treatments were performed in 2-week intervals for a total of five sessions. The final visit for the clinical evaluation was 2 weeks after the fifth treatment session. The mean number of papules, pustules, and comedones, and the melanin index, was significantly decreased at the final visit. However, sebum production and the erythema index showed no statistically significant differences after treatment. IPL treatment using a dual-band filter can be an alternative for patients who are unfit for systemic acne medication. It can also be used with conventional acne treatment for better treatment results.

Can a radiofrequency device reduce the pore size?

A facial pore is an empty funnel-shaped structure filled with cornified cylindrical plugs that can be cosmetically bothersome to some patients. In the previous report, the new unipolar radiofrequency (RF) device with a vacuum showed excellent skin tightening and patient satisfaction with improved pores. This study aims to confirm the treatment's efficacy with the new unipolar RF device on facial dilated pores by measuring quantitative sebum production differences and doing a histologic examination of pore size. Twelve patients who visited the dermatologic clinic without other underlying inflammatory facial skin diseases were included, regardless of the patient's age or sex. All patients received five successive treatments at 2-week intervals. We assessed all changes in sebum production levels, melanin index, erythema index before and after treatment, along with overall improvement (reduction of pore size, skin tone, skin texture, and skin laxity). In the five patients who agreed in advance, a biopsy of the pore lesion was taken before and 1 month after the last treatment with hematoxylin and eosin (H&E) staining, Masson's trichrome (M-T) staining, and Victoria blue staining. We observed a significant reduction of sebum production and melanin index after using the new unipolar RF device with a vacuum (sebum production, p = 0.011; MI, p = 0.004). In evaluating patient satisfaction for four categories, the patients showed a moderate to the excellent improvement of more than 50% in their condition except for skin tones. The average pore size decreased by 41.7% in the histological examination, from 64.98 to 37.86 µm. Additionally, we observed an overall decreased sebaceous gland in the dermis and the proliferation of dermal collagen fiber. The number of elastic bundles in the D-E junction was increased after treatment. The nonablative unipolar RF devices with a vacuum can improve dilated pores with a dual mechanism (collagen regeneration and reduction of sebum production), with much less pain than other RF devices.

Effect of the Recombinant Human Epidermal Growth Factor Ointment on Cutaneous Surgical Wounds Compared to Antibiotic Ointment.

BACKGROUND: Applying antibiotic ointment after skin surgery can decrease infection and improve scar. Epidermal growth factor (EGF) is known to be able to promote the growth and movement of epidermal cells to stimulate wound healing. Recombinant human EGF (rhEGF) ointment can be used in wet closed dressing to promotes wound healing and prevent complications by maintaining a wet environment. OBJECTIVE: To compare the efficacy of rhEGF ointment and conventional antibiotic ointment after cutaneous resection. METHODS: Patients who had excision procedures in two or more sites were enrolled. Each wound was assigned to the rhEGF group or the antibiotic ointment group. Wounds were subjected to Physician Global Assessment (PhGA), Patient Global Assessment (PGA), and Patient satisfaction assessment (PSA). The length and area of wounds, and melanin and erythema index (MI and EI) were also assessed for these wounds. RESULTS: Among 11 patients with a total of 20 pairs of resection sites, PhGA, PGA, MI, and EI showed no significant difference between rhEGF and antibiotic ointment groups. However, changes in length and area of wounds showed significant differences between the two groups. CONCLUSION: RhEGF ointment showed similar short-term cosmetic results with antibiotic ointment, and improved surgical results in regards of the wound size. Applying rhEGF could reduce the use of antibiotic ointments for cutaneous clean (class I) wound surgery.

Interleukin-13 Propagates Prothrombin Kringle-2-Induced Neurotoxicity in Hippocampi In Vivo via Oxidative Stress.

The present study investigated expression of endogenous interleukin-13 (IL-13) and its possible function in the hippocampus of prothrombin kringle-2 (pKr-2)-lesioned rats. Here we report that intrahippocampal injection of pKr-2 revealed a significant loss of NeuN-immunopositive (NeuN+) and Nissl+ cells in the hippocampus at 7 days after pKr-2. In parallel, pKr-2 increased IL-13 levels, which reached a peak at 3 days post pKr-2 and sustained up to 7 days post pKr-2. IL-13 immunoreactivity was seen exclusively in activated microglia/macrophages and neutrophils, but not in neurons or astrocytes. In experiments designed to explore the involvement of IL-13 in neurodegeneration, IL-13 neutralizing antibody (IL-13Nab) significantly increased survival of NeuN+ and Nissl+ cells. Accompanying neuroprotection, immunohistochemical analysis indicated that IL-13Nab inhibited pKr-2-induced expression of inducible nitric oxide synthase and myeloperoxidase within activated microglia/macrophages and neutrophils, possibly resulting in attenuation of reactive oxygen species (ROS) generation and oxidative damage of DNA and protein. The current findings suggest that the endogenous IL-13 expressed in pKr-2 activated microglia/macrophages and neutrophils might be harmful to hippocampal neurons via oxidative stress.

Photothermal therapy using gold nanoparticles for acne in Asian patients: A preliminary study.

Acne is a common skin disease that occurs in pilosebaceous units and is often prevalent in adolescence. There are many acne treatments, but they are associated with side effects, such as antibiotic resistance, teratogenicity, and irritation. Therefore, it is necessary to develop a more effective and safe alternative treatment for managing acne in patients of all ages. This study aimed to confirm the effect of gold photothermal therapy for acne. About 12 patients who visited the dermatologic clinic with moderate to severe acne vulgaris were included in the study, regardless of age or sex. All patients received three successive treatments at 1- to 2-week intervals with a photopneumatic device after applying the contents of a gold nanoparticle ample to the skin. Changes in the number of papules, pustules, and comedones before and after treatment, along with the overall improvement, were assessed. In four patients, a biopsy was taken before and 1 month after the last treatment. Significant reductions in acne lesions were observed after the use of gold photothermal therapy (papules, P = .001; pustules, P < .001; and comedones, P = .001). As noted in the Physician Global Assessment, the patients showed an average improvement of more than 50% in their condition. In the histopathological findings, a decrease in inflammatory cell infiltration and fibrotic changes of the dermis were observed after gold photothermal therapy. Gold photothermal therapy showed significant clinical and histological improvements in acne vulgaris in Asians without serious adverse effects.

Interleukin-4-Mediated Oxidative Stress Is Harmful to Hippocampal Neurons of Prothrombin Kringle-2-Lesioned Rat In Vivo.

The present study investigated the effects of reactive microglia/macrophages-derived interleukin-4 (IL-4) on hippocampal neurons in prothrombin kringle-2 (pKr-2)-lesioned rats. pKr-2 was unilaterally injected into hippocampus in the absence or presence of IL-4 neutralizing antibody (IL-4Nab). Immunohistochemical analysis showed a significant loss of Nissl+ and NeuN+ cells and activation of microglia/macrophages (increase in reactive OX-42+ and OX-6+ cells) in the hippocampus at 7 days after pKr-2 injection. The levels of IL-4 expression were upregulated in the reactive OX-42+ microglia/macrophages as early as 1 day, maximal at 3 days and maintained up to 7 days after pKr-2 injection. Treatment with IL-4Nab significantly increased neuronal survival in pKr-2-treated CA1 layer of hippocampus in vivo. Accompanying neuroprotection, IL-4 neutralization inhibited activation of microglia/macrophages, reactive oxygen species-derived oxidative damages, production of myeloperoxidase- and inducible nitric oxide synthase-derived reactive nitrogen species and nitrosative damages as analyzed by immunohistochemistry and hydroethidine histochemistry. These results suggest that endogenous IL-4 expressed on reactive microglia/macrophages mediates oxidative/nitrosative stress and play a critical role on neurodegeneration of hippocampal CA1 layer in vivo.

Delayed Treatment of Capsaicin Produces Partial Motor Recovery by Enhancing Dopamine Function in MPP+-lesioned Rats via Ciliary Neurotrophic Factor.

Transient receptor potential vanilloid subtype 1 (TRPV1) on astrocytes prevents ongoing degeneration of nigrostriatal dopamine (DA) neurons in MPP+-lesioned rats via ciliary neurotrophic factor (CNTF). The present study determined whether such a beneficial effect of astrocytic TRPV1 could be achieved after completion of injury of DA neurons, rather than ongoing injury, which seems more relevant to therapeutics. To test this, the MPP+-lesioned rat model utilized here exhibited approximately 70~80% degeneration of nigrostriatal DA neurons that was completed at 2 weeks post medial forebrain bundle injection of MPP+. TRPV1 agonist, capsaicin (CAP), was intraperitoneally administered. CNTF receptor alpha neutralizing antibody (CNTFRαNAb) was nigral injected to evaluate the role of CNTF endogenously produced by astrocyte through TRPV1 activation on DA neurons. Delayed treatment of CAP produced a significant reduction in amphetamine-induced rotational asymmetry. Accompanying this behavioral recovery, CAP treatment increased CNTF levels and tyrosine hydroxylase (TH) activity in the substantia nigra pars compacta (SNpc), and levels of DA and its metabolites in the striatum compared to controls. Interestingly, behavioral recovery and increases in biochemical indices were not reflected in trophic changes of the DA system. Instead, behavioral recovery was temporal and dependent on the continuous presence of CAP treatment. The results suggest that delayed treatment of CAP increases nigral TH enzyme activity and striatal levels of DA and its metabolites by CNTF endogenously derived from CAP-activated astrocytes through TRPV1, leading to functional recovery. Consequently, these findings may be useful in the treatment of DA imbalances associated with Parkinson's disease.

Interleukin-4 and Interleukin-13 Exacerbate Neurotoxicity of Prothrombin Kringle-2 in Cortex In Vivo via Oxidative Stress.

The present study investigated the effects of activated microglia-derived interleukin-4 (IL-4) and IL-13 on neurodegeneration in prothrombin kringle-2 (pKr-2)-treated rat cortex. pKr-2 was unilaterally injected into the Sprague-Dawley rat cerebral cortex and IL-4 and IL-13 neutralizing antibody was used to block the function of IL-4 and IL-13. Immunohistochemical analysis showed a significant loss of NeuN+ and Nissl+ cells and an increase of OX-42+ cells in the cortex at seven days post pKr-2. The levels of IL-4 and IL-13 expression were upregulated in the activated microglia as early as 12 hours post pKr-2 and sustained up to seven days post pKr-2. Neutralization by IL-4 or IL-13 antibodies (NA) significantly increased neuronal survival in pKr-2-treated rat cortex in vivo by suppressing microglial activation and the production of reactive oxygen species, as analyzed by immunohisotochemistry and hydroethidine histochemistry. These results suggest that IL-4 and IL-13 that were endogenously expressed from reactive microglia may play a critical role on neuronal death by regulating oxidative stress during the neurodegenerative diseases, such as Alzheimer's disease and dementia.

Effects of Silibinin Against Prothrombin Kringle-2-Induced Neurotoxicity in the Nigrostriatal Dopaminergic System In Vivo.

Parkinson's disease (PD) and Alzheimer's disease exhibit common features of neurodegenerative diseases and can be caused by numerous factors. A common feature of these diseases is neurotoxic inflammation by activated microglia, indicating that regulation of microglial activation is a potential mechanism for preserving neurons in the adult brain. Recently, we reported that upregulation of prothrombin kringle-2 (pKr-2), one of the domains that make up prothrombin and which is cleaved and generated by active thrombin, induces nigral dopaminergic (DA) neuronal death through neurotoxic microglial activation in the adult brain. In this study, we show that silibinin, a flavonoid found in milk thistle, can suppress the production of inducible nitric oxide synthase and neurotoxic inflammatory cytokines, such as interleukin-1ß and tumor necrosis factor-α, after pKr-2 treatment by downregulating the extracellular signal-regulated kinase signaling pathway in the mouse substantia nigra. Moreover, as demonstrated by immunohistochemical staining, measurements of the dopamine and metabolite levels, and open-field behavioral tests, silibinin treatment protected the nigrostriatal DA system resulting from the occurrence of pKr-2-triggered neurotoxic inflammation in vivo. Thus, we conclude that silibinin may be beneficial as a natural compound with anti-inflammatory effects against pKr-2-triggered neurotoxicity to protect the nigrostriatal DA pathway and its properties, and thus, may be applicable for PD therapy.

Inhibition of Microglia-Derived Oxidative Stress by Ciliary Neurotrophic Factor Protects Dopamine Neurons In Vivo from MPP⁺ Neurotoxicity.

We demonstrated that capsaicin (CAP), an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), inhibits microglia activation and microglia-derived oxidative stress in the substantia nigra (SN) of MPP⁺-lesioned rat. However, the detailed mechanisms how microglia-derived oxidative stress is regulated by CAP remain to be determined. Here we report that ciliary neurotrophic factor (CNTF) endogenously produced by CAP-activated astrocytes through TRPV1, but not microglia, inhibits microglial activation and microglia-derived oxidative stress, as assessed by OX-6 and OX-42 immunostaining and hydroethidine staining, respectively, resulting in neuroprotection. The significant increase in levels of CNTF receptor alpha (CNTFRα) expression was evident on microglia in the MPP⁺-lesioned rat SN and the observed beneficial effects of CNTF was abolished by treatment with CNTF receptor neutralizing antibody. It is therefore likely that CNTF can exert its effect via CNTFRα on microglia, which rescues dopamine neurons in the SN of MPP⁺-lesioned rats and ameliorates amphetamine-induced rotations. Immunohistochemical analysis revealed also a significantly increased expression of CNTFRα on microglia in the SN from human Parkinson's disease patients compared with age-matched controls, indicating that these findings may have relevance to the disease. These data suggest that CNTF originated from TRPV1 activated astrocytes may be beneficial to treat neurodegenerative disease associated with neuro-inflammation such as Parkinson's disease.

Upregulation of neuronal astrocyte elevated gene-1 protects nigral dopaminergic neurons in vivo.

The role of astrocyte elevated gene-1 (AEG-1) in nigral dopaminergic (DA) neurons has not been studied. Here we report that the expression of AEG-1 was significantly lower in DA neurons in the postmortem substantia nigra of patients with Parkinson's disease (PD) compared to age-matched controls. Similarly, decreased AEG-1 levels were found in the 6-hydroxydopamine (6-OHDA) mouse model of PD. An adeno-associated virus-induced increase in the expression of AEG-1 attenuated the 6-OHDA-triggered apoptotic death of nigral DA neurons. Moreover, the neuroprotection conferred by the AEG-1 upregulation significantly intensified the neurorestorative effects of the constitutively active ras homolog enriched in the brain [Rheb(S16H)]. Collectively, these results demonstrated that the sustained level of AEG-1 as an important anti-apoptotic factor in nigral DA neurons might potentiate the therapeutic effects of treatments, such as Rheb(S16H) administration, on the degeneration of the DA pathway that characterizes PD.

Protection of nigral dopaminergic neurons by AAV1 transduction with Rheb(S16H) against neurotoxic inflammation in vivo.

We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson's disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2). Our observations showed that Rheb(S16H) transduction played a role in the neuroprotection of the nigrostriatal DA system against pKr-2-induced neurotoxic inflammation, even though there were similar levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1ß), in the AAV1-Rheb(S16H)-treated substantia nigra (SN) compared to the SN treated with pKr-2 alone; the neuroprotective effects may be mediated by the activation of neurotrophic signaling pathways following Rheb(S16H) transduction of nigral DA neurons. We conclude that AAV1-Rheb(S16H) transduction of neuronal populations to activate the production of neurotrophic factors and intracellular neurotrophic signaling pathways may offer promise for protecting adult neurons from extracellular neurotoxic inflammation.