Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the PCD evaluation and diagnosis framework, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

Idiopathic CD4 Lymphopenia is a heterogeneous condition, recognized in the late 20th century, with a wide spectrum of presentations, requiring a high index of suspicion to avoid misdiagnosing the condition. This case highlights the diversity in its clinical presentations in the context of an autosomal dominant pattern of inheritance. We are reporting a case of a nine-year-old child, initially labelled by her primary treating hospital as primary ciliary dyskinesia after presenting with chronic cough, purulent nasal discharge, and recurrent chest infections. She was referred to our facility, a tertiary center, as her condition marginally improved. After the patient has undergone a comprehensive diagnostic workup, including a gene study, she was found to be carrying a mutation known to cause idiopathic CD4 lymphopenia. Extended work up of her family showed that two of her siblings have inherited an autosomal dominant mutation from their mother who had a milder form of the disease. This condition is an extremely rare condition in children, which can be easily mislabeled. Thus, healthcare providers should avoid labeling certain long-standing diseases unless the diagnosis has been established. We encourage leveraging the use of the latest revolutionary genetic testing techniques to confirm the diagnosis of such puzzling cases.

We report a Japanese 5-year-old boy with primary ciliary dyskinesia (PCD) which was diagnosed owing to Clostridium difficile (CD) infection caused by prolonged antibiotic exposure. He had intractable otitis media with effusion (OME) and had abdominal pain and diarrhea for 4 months after starting antibiotics administration. His stool contained CD toxin. After vancomycin treatment, his symptoms improved and his stools did not contain CD toxin. His past medical history included frequent pneumonia. We, therefore, performed electron microscopy of the biopsy specimen from his nasal mucosa and genetic testing, and he was diagnosed with PCD. PCD is a rare inherited genetic disease causing ciliary dysfunction, which is very difficult to diagnose because some children without PCD also develop the same symptoms. Therefore, children who have intractable OME, rhinosinusitis, frequent pneumonia, or bronchitis and are taking antibiotics for long periods of time should be checked for underlying diseases, such as PCD.

BACKGROUND: Patients with recurrent epistaxis, particularly due to hereditary hemorrhagic telangiectasia (HHT) are recommended to apply topical tranexamic acid (TXA) to reduce bleeding events. Those patients may suffer ciliary dysfunction due to TXA\'s effects on ciliary beating frequency (CBF) and their consequences.
RESULTS: Human nasal epithelial cells were harvested with a nasal brush in 30 healthy subjects. We investigated the CBF in RPMI medium using high-frequency video microscopy. TXA was added to the cells in various concentrations ranging from 2 to 5%, including the therapeutic concentration (2%) and a control (0%).
RESULTS: CBF in the control condition was 6.1 ± 1.6 Hz. TXA reduces CBF in a time and concentration dependent manner, to, e.g. 4.3 ± 1.2 Hz with 2% TXA and 3.3 ± 0.9 Hz with 5% TXA after 16-20 min. The differences in CBF were statistically significant for all concentrations of TXA.
CONCLUSIONS: TXA has the potential to significantly impair nasal epithelial function. Therefore, frequent or regular topical nasal application of TXA should be done under close monitoring of nasal function, especially in patients with co-morbidities like chronic rhinosinusitis.

In recent years, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has emerged as a substitute for PFOS with large demand and application in the Chinese market. However, little is known about potential developmental effects of OBS. In this study, zebrafish embryos were acutely exposed to different concentrations of OBS and the positive control PFOS for a comparative developmental toxicity assessment. OBS caused hatching delays, body axis curvature, neurobehavioral inhibition and abnormal cardiovascular development. These organismal effects were accompanied by change of development related genes expression profile, in which some cases were similar to PFOS. Overall, the toxic effects induced by OBS were generally milder than that of PFOS. Further investigation suggested that both OBS and PFOS disrupted ciliogenesis, evidenced by the ciliary immunostaining, changes in gene expression of kinesin family, dynein arm family and tubulin family members, as well as downregulation of the abundance of motor proteins including KIF3C, DYNC1H1 and DYNC1LI1. The influence of PFOS was stronger than that of OBS on ciliary genes and proteins. Molecular docking analysis revealed that both OBS and PFOS fitted into the motor proteins tightly, but binding affinity between OBS and motor proteins was lower than PFOS. Collectively, OBS and PFOS may act on ciliary motor proteins to interfere with ciliogenesis, leading to ciliary dysfunction and providing a novel probable action mode linked to developmental toxicity. This raises concerns regarding the health risks of the novel PFOS alternative OBS.

UNASSIGNED: Primary Ciliary Dyskinesia (PCD) is an autosomal recessive disease, characterized by ciliary dysfunction and impaired mucociliary clearance. Previous studies have indicated a low physical fitness in PCD patients but currently it is not known whether physical training beneficially affects fitness, inflammatory markers and quality of life.
UNASSIGNED: The patient was a Caucasian male (67.0 kg, 183.3 cm), born in 1984 and was diagnosed with the Kartagener Syndrome (i.e. PCD) right after birth. He was prescribed structured physical training over a period of almost two years (from August 2017-June 2019) and was assessed regularly. Aerobic fitness improved throughout the intervention period, but no systematic changes were observed in inflammatory markers and overall quality of life.
UNASSIGNED: Our data provides reasoning to stress the implementation of structured physical training to enhance physical performance also in the management of PCD.

Chronis rhinosinusitis is considered as a widespread public health issue with a prevalence of 10%. The disease significantly reduces quality of life and increases the risk of cardiovascular diseases as well as certain forms of cancer. Alteration of mucociliary clearance frequently observed in the patients and plays a significant role in disease pathogenesis. Certain studies have demonstrated that patients with chronic rhinosinusitis are characterized by significant reduction of essential trace elements and toxic metal overload. However, the particular mechanisms of the role of trace element dysbalance in chronic rhinosinusitis are unclear. We hypothesize that exposure to toxic trace elements (arsenic, nickel, cadmium) damages ciliary mucosal epithelium thus affecting mucociliary transport. In turn, altered mucociliary transport results in reduced removal of the inhaled metal-containing particles from nasal mucosa leading to their absorption and further aggravation of toxicity. Essential trace elements (zinc, selenium) play a significant role in regulation of mucociliary transport and immunity, thus their deficiency (either dietary or due to antagonism with toxic metals) may be associated with impaired functions and increased toxic metal toxicity. Therefore, a vicious circle involving metal accumulation and toxicity, essential element deficiency, impairment of mucociliary transport and metal particle removal, resulting in further accumulation of metals and aggravation of toxic effects is formed. The present hypothesis is supported by the findings on the impact of trace elements especially zinc and arsenic on mucociliary clearance, the role of mucociliary transport in heavy metal particles elimination from the airways, trace element dysbalance in chronic rhinosinusitis, as well as toxic and essential metal antagonism. The data from hypothesis testing and its verification may be used for development of therapeutic approach for management of chronic rhinosinusitis. Particularly, the use of essential elements (zinc, selenium) may reduce toxic metal toxicity thus destroying the vicious circle of heavy metal exposure, toxicity, alteration of mucociliary clearance, and aggravation of chronic rhinosinusitis. Essential element supplementation may be considered as a tool for management of chronic refractory rhinosinusitis. In addition, analysis of essential and toxic trace element status may provide an additional diagnostic approach to risk assessment of chronic rhinosinusitis in highly polluted environments.

For all intents and purposes, craniofacial development is initiated as soon as the anteroposterior axis of an embryo is established. Although the neural crest receives a significant amount of attention, craniofacial tissue has more patterning information than other tissues of the body. New studies have further clarifi ed the contribution of ciliary epithelia as a source of patterning information for the face. In this paper, we review the craniofacial anomalies in patients with ciliopathies, in which orofacial region is a pivotal recognition of the disorder. Also, a case report of a patient with suspected ciliopathy has been presented along with a logical approach for diagnosis of such disorders.

BACKGROUND: Primary ciliary dyskinesia (PCD) is generally a recessively inherited disorder characterized by dysfunction of motile cilia. A mutation in a new causative gene (CCDC39) has been identified in the Old English Sheepdog (OES).
OBJECTIVE: To describe the clinical findings and the molecular changes of affected dogs and estimate the worldwide prevalence of the mutation in a large cohort of OES.
METHODS: 578 OES, including 28 affected and 550 clinically healthy dogs.
METHODS: This retrospective study reviewed the data of OES diagnosed with PCD and OES tested for the mutation. Clinical data including results of physical examination and further investigations were obtained on 11/28 dogs. CCDC39 expression was assessed by qRT-PCR and Western blot analysis in affected dogs and healthy dogs. DNA was extracted on 561/578 dogs and a genetic test by Taqman technology was developed to genotype the CCDC39 mutation in these dogs.
RESULTS: Clinical findings were recurrent nasal discharge and cough, pyrexia, leucocytosis, and bronchopneumonia. Ultrastructural defects were characterized by central microtubular abnormalities and decreased number of inner dynein arms (IDAs). Molecular analysis revealed a reduced expression of CCDC39 RNA and an absence of CCDC39 protein in affected dogs compared to healthy dogs. The mutation was more frequent in nonrandomly selected European OES population with a higher proportion of carriers (19%) compared to non-European dogs (7%).
CONCLUSIONS: CCDC39 mutation is dispersed in a worldwide population and is responsible for PCD in this breed. Genetic testing might enable control of this disease.

Previously we have shown that chronic alcohol intake causes alcohol-induced ciliary dysfunction (AICD), leading to non-responsive airway cilia. AICD likely occurs through the downregulation of nitric oxide (NO) and cyclic nucleotide-dependent kinases, protein kinase G (PKG) and protein kinase A (PKA). Studies by others have shown that dietary supplementation with the antioxidants N-acetylcysteine (NAC) and procysteine prevent other alcohol-induced lung complications. This led us to hypothesize that dietary supplementation with NAC or procysteine prevents AICD. To test this hypothesis, C57BL/6 mice drank an alcohol/water solution (20% w/v) ad libitum for 6 weeks and were concurrently fed dietary supplements of either NAC or procysteine. Ciliary beat frequency (CBF) was measured in mice tracheas, and PKG/PKA responsiveness to β-agonists and NOx levels were measured from bronchoalveolar lavage (BAL) fluid. Long-term alcohol drinking reduced CBF, PKG and PKA responsiveness to β-agonists, and lung NOx levels in BAL fluid. In contrast, alcohol-drinking mice fed NAC or procysteine sustained ciliary function and PKG and PKA responsiveness to β-agonists. However, BAL NO levels remained low despite antioxidant supplementation. We also determined that removal of alcohol from the drinking water for as little as 1 week restored ciliary function, but not PKG and PKA responsiveness to β-agonists. We conclude that dietary supplementation with NAC or procysteine protects against AICD. In addition, alcohol removal for 1 week restores cilia function independent of PKG and PKA activity. Our findings provide a rationale for the use of antioxidants to prevent damage to airway mucociliary functions in chronic alcohol-drinking individuals.