Sensitivity analysis and parameters estimation for the transmission of lymphatic filariasis.

Lymphatic filariasis is a neglected tropical disease which poses public health concern and socio-economic challenges in developing and low-income countries. In this paper, we formulate a deterministic mathematical model for transmission dynamics of lymphatic filariasis to generate data by white noise and use least square method to estimate parameter values. The validity of estimated parameter values is tested by Gaussian distribution method. The residuals of model outputs are normally distributed and hence can be used to study the dynamics of Lymphatic filariasis. After deriving the basic reproduction number, R0 by the next generation matrix approach, the Partial Rank Correlation Coefficient is employed to explore which parameters significantly affect and most influential to the model outputs. The analysis for equilibrium states shows that the Lymphatic free equilibrium is globally asymptotically stable when the basic reproduction number is less a unity and endemic equilibrium is globally asymptotically stable when R0≥1. The findings reveal that rate of human infection, recruitment rate of mosquitoes increase the average new infections for Lymphatic filariasis. Moreover, asymptomatic individuals contribute significantly in the transmission of Lymphatic filariasis.

False-negative real-time polymerase chain reaction tests in COVID-19 patients: an epidemiological analysis of 302 patients.

OBJECTIVES: Patients who arrive at the emergency department (ED) with COVID-19, who test negative at the first real-time polymerase chain reaction (RT-PCR), represent a clinical challenge. This study aimed to evaluate if the clinical manifestation at presentation, the laboratory and imaging results, and the prognosis of COVID-19 differ in patients who tested negative at the first RT-PCR compared with those who tested positive and also to evaluate if comorbid conditions patient-related or the period of arrival are associated with negative testing. STUDY DESIGN: We retrospectively collected clinical data of patients who accessed the ED from March 1 to May 15, 2020. METHODS: We compared clinical variables, comorbid conditions, and clinical outcomes in the two groups by univariate analysis and logistic regression. RESULTS: Patients who tested negative at the first RT-PCR showed a higher prevalence of cardiopathy, immunosuppression, and diabetes, as well as a higher leukocyte and lower lymphocyte counts compared with patients who tested positive. A bilateral interstitial syndrome and a typical pattern at computed tomography scan were prevalent in the test-negative group. Test-negative patients were more likely to be admitted to the hospital but less likely to need admission in a high level of care ward. The false-negative rate increased from March to May. CONCLUSION: False-negative RT-PCR COVID-19 patients present a similar spectrum of symptoms compared with positive cohort, but more comorbidities. Imaging helps to identify them. True positives had a higher risk of serious complications.

Financial Costs of the Zanzibar Elimination of Schistosomiasis Transmission Project.

We estimated the financial costs of different interventions against urogenital schistosomiasis, implemented by the Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project, on Pemba and Unguja islands, Tanzania. We used available data on project activities, resources used, and costs reported in the accounting information systems of ZEST partners. The costs were estimated for all the activities related to snail control, behavior change interventions, the impact assessment surveys, and management of the whole program. Costs are presented in US$ for the full duration of the ZEST project from 2011/2012 to 2017. The total financial costs of implementing snail control activities over 5 years, excluding the costs for donated Bayluscide, were US$55,796 on Pemba and US$73,581 on Unguja, mainly driven by personnel costs. The total financial costs of implementing behavior change activities were US$109,165 on Pemba and US$155,828 on Unguja, with costs for personnel accounting for 47% on Pemba and 69% on Unguja. Costs of implementing biannual mass drug administration refer to the estimated 2.4 million treatments provided on Pemba over 4 years (2013-2016), and do not include the costs of donated praziquantel. The total cost per provided treatment was, on average, US$0.21. This study showed the value of exploiting administrative data to estimate costs of major global health interventions. It also provides an evidence base for financial costs and main cost drivers of implementing multiple combinations of intervention sets that inform decisions regarding the feasibility and affordability of implementing schistosomiasis control and elimination strategies.

Rhizospheric bacterial isolates of grass pea (Lathyrus sativus L.) endowed with multiple plant growth promoting traits.

AIM: The main aim of this work was to examine the plant growth promoting, biocontrol activities and stress competency of grass pea rhizobacterial strains from Ethiopia. METHODS AND RESULTS: Serial dilutions were carried out to isolate rhizobacterial strains from the rhizosphere soil samples. The isolates were characterized for their plant growth promoting, biocontrolling and stress tolerance potential. The isolates that showed better performance in the tested parameters were identified by 16S rRNA gene sequencing. Among the isolates tested on Pikovskaya agar medium, 22 isolates that showed solubilization index of >2·41 cm were selected for further screening tests. Isolate AAUGPR-53 identified as Enterococcus species, Enterococcus casseliflavus strain showed the highest phosphate solubilization index and indole-3-acetic acid production efficiency of 4·81 ± 0·02 (µg ml-1 ) and 56·55 ± 0·45 (µg ml-1 ), respectively. Sixteen (72·7%) of the isolates showed in vitro antifungal inhibition against Fusarium oxysporum f. sp. lentis with isolates AAUGPR-92 and AAUGPR-91 identified as Enterococcus species, E. casseliflavus strain and Enterococcus gallinarum strain exhibiting the highest inhibition of 83 and 78%, respectively. Likewise, 68·2%, 91·30%, 45·5%, 77·3% and 100% of the isolates produced chitinase, protease, cellulase, HCN and NH3 , respectively. Most of the isolates showed good tolerance to the tested stress factors. The 16S rRNA partial sequencing of the rhizobacterial isolates proved their taxonomic position in the existing bacterial isolates. CONCLUSION: The results indicated that three strains, AAUGPR-53, 91 and 92, that showed maximum sequence identity (99%) to Enterococcus species, E. casseliflavus and E. gallinarum were recommended as microbial inoculants for trials under greenhouse and field conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study illustrates an effective alternative to conventional fertilizers that may contribute to crop disease reduction. Our results provide a foundation for future research that will lead to identifying potentially useful biocontrol strains found in the rhizosphere of grass pea.

Fetal growth patterns in Beckwith-Wiedemann syndrome.

We provide data on fetal growth pattern on the molecular subtypes of Beckwith-Wiedemann syndrome (BWS): IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age-corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1-GoM (n = 21), UPD (n = 87), IC2-LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1-GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1-GoM patients, lowest in IC2-LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2-LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1-GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2-LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2-LoM, but manifest a body mass disproportion rather similar to that seen in IC1-GoM cases.

(Epi)genotype-phenotype correlations in Beckwith-Wiedemann syndrome: a paradigm for genomic medicine.

Beckwith-Wiedemann syndrome (BWS) is the commonest overgrowth cancer predisposition disorder and represents a model for human imprinting dysregulation and tumorigenesis. BWS features can variably combine and present a widely variable range of severity in the phenotypic expression. This wide spectrum is paralleled at molecular level by complex (epi)genetic defects on chromosome 11p15.5 leading to disrupted expression of imprinted genes controlling growth and cellular proliferation. In this review, we outline the spectrum of clinical manifestations of BWS analyzing their (epi)genotype-phenotype correlations. The differences observed in the phenotypic profiles of BWS molecular subtypes allow a composite view of this syndrome with implications on clinical care, diagnosis, follow-up, and management, and provide directions for future disease monitoring.

Subclinical hyperthyroidism when presenting as initial manifestation of juvenile Hashimoto's thyroiditis: first report on its natural history.

BACKGROUND: Due to the lack of specific pediatric studies, no data are available about natural history of endogenous subclinical hyperthyroidism (SH) in childhood. AIMS: (a) To investigate for the first time the natural history of SH [suppressed thyrotropin (TSH) and normal free thyroxine free thyroxine (FT4) levels] when presenting as initial manifestation of Hashimoto's thyroiditis (HT) in childhood (group A); (b) to compare spontaneous evolution of HT-related SH with that observed in age-matched patients with HT-related frank hyperthyroidism (suppressed TSH and elevated FT4 levels), i.e., Hashitoxicosis Htx (group B). RESULTS: In the 11 patients of group A, TSH normalization spontaneously occurred 1-24 months after diagnosis, while in the 10 patients of group B it occurred 3-9 months after diagnosis, with no differences between the 2 groups in terms of time interval from entry to TSH normalization. In group A, this time interval was related to baseline thyroid peroxidase antibodies (r=0.78, p = 0.04). During follow-up, eight patients of each group remained euthyroid, whereas two became hypothyroid (in both groups) and one developed Graves' disease (in group A). CONCLUSION: (a) HT should be included among the causes of endogenous SH in pediatric age; (b) in children with HT-related SH, spontaneous normalization of TSH levels occurs within the first 24 months after diagnosis, as well as in age-matched patients with Htx; (c) in both these conditions, a further deterioration of thyroid function might re-present in some patients during follow-up; (d) Ht-related SH and Htx might be possibly seen as different biochemical stages along the same continuum.

Phalangeal quantitative ultrasound in 1,719 children and adolescents with bone disorders.

SUMMARY: We measured bone properties by phalangeal quantitative ultrasound in 1,719 pediatric patients with bone disorders, classifying them according to fracture status. Quantitative ultrasound discriminated fractured and nonfractured pediatric patients and enabled us to stratify fractured patients into classes according to the severity of the causative trauma (spontaneous, minimal trauma, appropriate trauma fractures). INTRODUCTION: The correlation between quantitative bone measurements and fractures is poorly established in pediatric patients with bone disorders. We correlated phalangeal quantitative ultrasound (QUS) and fracture history in children and adolescents with bone disorders and evaluated the ability of QUS to recognize fractured patients. METHODS: Amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were measured in 1,719 pediatric patients with bone disorders and related to fracture history. The patients were classified as (1) spontaneously (77), (2) minimal trauma (101), or (3) appropriate trauma fractured (206), and (4) nonfractured (1,335). The likelihood of fracture according to QUS was calculated as odds ratio per SD decrease (OR/SD), and the effectiveness in discriminating fractured patients was evaluated by receiver operating characteristic (ROC) analysis. The influence of age, sex, puberty, height, and BMI was explored by respective adjustments and multiple logistic regression. RESULTS: Fractured patients showed significantly reduced AD-SoS and BTT standard deviation score (-0.32 ± 1.54 and -0.78 ± 1.49) compared to nonfractured subjects (0.43 ± 1.63 and -0.11 ± 1.34). QUS measurements paralleled the causative trauma severity, ranging from the lowest values in spontaneously fractured patients to normal values in appropriate trauma fractured subjects. The OR/SD were increasingly higher in appropriate trauma fractured, minimal trauma fractured, and spontaneously fractured patients. At ROC analysis, both parameters proved to have significant discrimination power in recognizing spontaneously and minimal trauma-fractured patients. CONCLUSIONS: QUS identifies fractured pediatric patients with bone disorders, reflecting the severity of the causative trauma with a high discrimination power for fragility fractures.

Mantle cell lymphoma of the colon with massive splenomegaly: A case report.

We describe colonoscopic features in a 77-year-old female with relapse of mantle cell lymphoma, who presented with a history of rectal bleeding of 2 months' duration. Her initial colonoscopy 3 years prior to the current presentation had revealed no gross lesions of mantle cell lymphoma; however, there was evidence of microscopic disease at that time as well. The patient had now developed classical lesions following relapse of the disease. The present case report gives the natural history of this rare tumour. The comparative colonoscopic features with a brief review of mantle cell lymphoma are presented.

Prenatal features of Noonan syndrome: prevalence and prognostic value.

OBJECTIVE: Noonan syndrome (NS) is a common autosomal dominant developmental disorder, mainly characterized by congenital heart defects, short stature, and a variable degree of developmental delay. We have reviewed the prenatal findings in NS and we have correlated them with genotype and postnatal phenotype. METHODS: The cohort consisted of 47 patients with molecular diagnosis of NS. Prenatal and postnatal phenotypes were assessed by analysis of medical records, and clinical follow-up. Postnatal clinical phenotype, congenital heart disease, neuropsychomotor development, and growth pattern were arbitrarily scored in terms of severity. RESULTS: Mean age at diagnosis of NS was 7 years (ranging from birth to 38 years). Abnormal maternal serum triple screen was present in 36% of cases, nuchal translucency > 2.5 mm in 41%, polyhydramnios in 38% and fetal anomalies at prenatal ultrasonography in 21%. No statistical association was observed between prenatal findings and NS genotype or scores of postnatal clinical phenotype, congenital heart disease, neuropsychomotor development, or short stature. Presence of morphologic fetal anomalies at ultrasonography was associated with developmental delay/intellectual disabilities (p < 0.001) and juvenile myelomonocytic leukaemia (p = 0.006). CONCLUSIONS: Abnormal prenatal findings are frequent in NS pregnancies, though they are not specific and most are not useful for the prediction of the postnatal phenotype.

Fast screening of depression in cancer patients: the effectiveness of the HADS.

In oncology clinics, there is an increasing need for fast and accurate screening scales and procedures in order to evaluate cancer patients for depression. The present study investigated the comparative effectiveness in recognising depressed patients of the Hospital Anxiety and Depression Scale (HADS), a self-report screening scale, and the Montgomery-Asberg Depression Rating Scale (MADRS), a semi-structured clinician-rated scale, in 151 patients affected by mixed cancer pathologies. With the MADRS, 73.5% of the patients were identified as depressed, whereas the HADS identified 36.4% and 58.3% as depressed, using the cut-offs of 11 and 8 respectively. The results suggest moderate agreement between the MADRS and the HADS when a cut-off of 8 is used (K-test: 0.44), while using a HADS cut-off of 11 gave a significantly higher underestimation of depressed patients (K-test: 0.29). In conclusion, the results suggest that the HADS can be useful as a sufficiently accurate first-step screening tool for depression in mixed oncology settings.

Metabolic syndrome in children with Prader-Willi syndrome: the effect of obesity.

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS), the most frequent syndromic obesity, is associated with elevated morbidity and mortality in pediatric and adult ages. In PWS, the presence of metabolic syndrome (MS) has not yet been established. The aim of the study was to estimate the frequency of MS and its components in pediatric subjects according to obesity status. METHODS AND RESULTS: A cross-sectional study was performed in 109 PWS children aged 2-18 years (50 obese and 59 non-obese) and in 96 simple obese controls matched for age, gender, and also for BMI with obese PWS. Obesity was defined when SDS-BMI was >2. Non-obese PWS showed significantly lower frequency of hypertension (12%) than obese PWS (32%) and obese controls (35%)(p=0.003). The same was observed for low HDL-cholesterol (3% vs 18% and 24%, p=0.001) and high triglycerides (7% vs 23% and 16%, p=0.026). Frequency of altered glucose metabolism was not different among groups (2% vs 10% and 5%), but type 2 diabetes (four cases) was present only in obese PWS. Non-obese PWS showed lower insulin and HOMA-index respect to obese PWS and obese controls (p ≤ 0.017). Overall MS frequency in PWS was 7.3%. None of the non-obese PWS showed MS compared with 16% of obese PWS and controls (p<0.001). When obesity was excluded from the analysis, a significantly lower frequency for clustering of ≥ 2 factors was still found in non-obese PWS (p=0.035). CONCLUSION: Non-obese PWS showed low frequency of MS and its components, while that observed in obese PWS was very close to those of obese controls, suggesting the crucial role of obesity status. Prevention of obesity onset remains the most important goal of PWS treatment. Early identification of MS could be helpful to improve morbidity and mortality in such patients.

Some factors associated with non-adherence to antiretroviral therapy (ART) in people living with HIV/AIDS (PLHA) in Tanzania: a case study of Dar es Salaam region.

OBJECTIVES: Tanzania is one of the nations that are highly affected by HIV/AIDS epidemic. Invention of ARVs (Anti -Retroviral) brought hope of extended life to people living with HIV/AIDS (PLHA). Though ARV's are administered in several clinics particularly in Dar es Salaam, there is a problem to adherence. Some factors associated with non-adherence are investigated and ways to optimize adherence are suggested. METHODS: This study was undertaken at three treatment and care clinics in Dar es Salaam. A sample of 197 individuals on ARV and 30 health care providers were interviewed. The sample comprised of 76 % females and 24% males, with mean age 34. About 74% of individuals on ARV were aged between 25 - 45 years. Logistic Regression and survival analysis models were used in the analysis. RESULTS: Individuals on ARV recommended factors responsible for non-adherence as lack of awareness 63.5%, stigma 56%, side effects 53.3%, and costs 28%. Other factors were being busy 25.4%, away from home 21.3%, forgetting 12.2% and ARVs out of stock 10.2%. Proportion of PLHA lost to follow up was 26%. Awareness and side effects were found to be statistically significant, with p-values of 0.042 and 0.068 respectively (alpha = 0.1). The median survival time for individuals on ARV was 42 months (95% CI: 41-44) with survival rate of above 0.7. Log-rank test showed significant differences between the male and female on having a shorter time to death. Females seemed to survive longer than males suggesting that females adhere more to ART than males. CONCLUSION: This calls for emphasis on HIV/AIDS education to the society especially to sensitize men. Another suggestion is that when a woman gets pregnant, both the expectant mother and father should attend maternal clinic so that they both take HIV test so as to increase man's participation.

Immunostimulation to reduce recurrence after surgery for anal condyloma acuminata: a prospective randomized controlled trial.

AIM: Human papillomavirus is the most common cause of sexually transmitted disease. It is associated with immunosuppression and shows a marked tendency to recur. We investigated a natural immunostimulant aimed to reduce recurrence. METHOD: A randomized controlled study was carried out including 261 patients allocated to surgical excision alone (control group; n = 122) and surgical excision plus postoperative immunostimulation for 30 days with a natural product (STET; study group; n = 139). Patients with HIV positivity were excluded. All patients gave fully informed consent. RESULTS: The patients were followed for 6 months after surgery. Recurrence occurred in 7.2% (10/139) in the study group and in 27.1% (33/122) in the control group (P < 0.0001). There were no significant differences in the sex, sexual orientation, number of lesions, time to diagnosis and treatment or localization of lesions in the two groups. CONCLUSIONS: Immunostimulation using a natural product significantly reduced the incidence of recurrence of anal condylomata in patients undergoing surgical excision.

Sperm count of young men surgically treated for cryptorchidism in the first and second year of life: fertility is better in children treated at a younger age.

INTRODUCTION: Recent data has indicated the usefulness of performing orchiopexy in the first years of life. In this study, we evaluated testicular function in young men operated on for cryptorchidism in the first year of life. To our knowledge, this is the first report on the effects of such an early treatment. MATERIALS AND METHODS: Testicular function was assessed in a group of young men operated for cryptorchidism during the first year of life (Group A, n=13) and during the second year of life (Group B, n=16). RESULTS: Total sperm counts were clearly higher in Group A (52.3+/-14.3 million/ml vs. 30.4+/-23.5 million/ml, p=0.005) as was sperm motility (36.2+/-8.7 vs. 23.1+/-15.7%, p=0.009). A clear inverse relationship was found between age at orchiopexy and total sperm count (r=-0.394, p=0.034) and sperm motility (r=-0.382, p=0.041). The relationship between volume of testes, position at surgery, uni/bilaterality of cryptorchidism, evidence of Ad spermatogonia at biopsy performed during surgery and treatment with LHRH and hCG performed before surgery and fertility was not significant. The latter findings may be partially explained by the low number of patients participating in the study and need further investigation. CONCLUSIONS: We obtained, for the first time, results showing the benefit of treating cryptorchidism during the first year of life rather than in the second year or even later.

Dopamine agonists in 6-pyruvoyl tetrahydropterin synthase deficiency.

OBJECTIVE: To report the efficacy, tolerability, and safety of the dopamine agonist pramipexole in a series of 5 patients affected by inherited 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency and needing l-3,4 dihydroxyphenylalanine (l-dopa) therapy. METHODS: Patients included 4 males and 1 female with ages ranging from 2 to 26 years. Their medication included tetrahydrobiopterin (BH4), 5-hydroxytryptophan, l-dopa, carbidopa, selegiline, and entacapone. All experienced residual symptoms of dopamine deficiency, movement and behavioral disability, and complications of l-dopa therapy, associated with fluctuating hyperprolactinemia. Patients had full assessment of clinical and biochemical condition, including evaluation by an adapted Unified Parkinson's Disease Rating Scale (UPDRS) and measurement of plasma prolactin (PRL) and catecholamines, before and after a 6-week trial with pramipexole. Pramipexole was administered twice daily as an adjunct to l-dopa therapy in dosages upwardly titrated, with a concurrent reduction of l-dopa dosage. Clinical follow-up went on for 1 year. RESULTS: Pramipexole was well tolerated by all patients, with marked improvement and stabilization of their clinical picture. The mean improvement on the total UPDRS score was 43% (range 33.3%-55.6%) from baseline. Diurnal profiles of plasma PRL normalized and plasma catecholamine levels lasted unchanged. The daily administrations of l-dopa were curtailed from 3 or 4 to 2, and the l-dopa dosage was reduced up to 40%. CONCLUSIONS: The addition of pramipexole to the treatment of 6-pyruvoyl tetrahydropterin synthase deficiency improves the results of l-3,4 dihydroxyphenylalanine therapy. Similar benefits may be expected in other forms of inherited tetrahydrobiopterin deficiency.

Feasibility of the sentinel node biopsy in anal cancer.

AIM: Anal cancer is a rare neoplasm. According to a European Organization for Research and Treatment of Cancer multivariate analysis, synchronous inguinal lymph node metastasis occurs in 10-25% of patients and constitutes an independent prognostic factor for local failure and overall mortality. METHODS: Inguinal lymph node status was assessed using the sentinel node technique in 35 patients with anal cancer. RESULTS: Histology revealed 23 squamous carcinomas, 10 basaloid carcinomas, 1 squamous carcinoma with basaloid areas and 1 spinocellular epithelioma associated with areas of Bowen's disease. Disease stage was T1 in 5 patients, T2 in 18, T3 in 11 and T4 in 1 patient. Lympho-scintigraphy using a GE Millennium gamma camera was performed after peritumoral injection of 37 MBq of 99mTc colloid. Surgical sentinel node biopsy with a portable Scintiprobe MR 100 (Politech, Carsoli, Italy) had a detection rate of 97.1%. Inguinal metastases were detected in 7 (20%) patients, in 2 of which metastasis was bilateral. CONCLUSIONS: Given the correlation between prognosis and node involvement, sentinel node biopsy can be considered a simple method for adequate pretreatment staging of anal carcinoma. Use of the technique could avert the need for prophylactic inguinal radiotherapy in N0-N1 patients, thus reducing the morbidity associated with inguinal radiotherapy. Consistent follow-up is required to evaluate long-term results:

Increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells in phenylketonuria.

Phenylketonuria (PKU) is commonly complicated by a progressive bone impairment of uncertain aetiology. The therapeutic phenylalanine (Phe)-restricted diet and the possible noxious effects of high plasma Phe concentrations on bone have previously been suggested as possible determinant factors. Since osteoclasts are involved in bone reabsorption, they could play a role in determining bone damage in PKU. The reported increased excretion of bone resorption markers in PKU patients is consistent with this hypothesis. Although different diseases characterized by bone loss have been related to increased spontaneous osteoclastogenesis from peripheral blood mononuclear cells (PBMCs), to date there is no evidence of increased osteoclast formation in PKU. In this study, we compared the spontaneous osteoclastogenesis from PBMCs in 20 patients affected by PKU with that observed in age- and sex-matched healthy subjects. Phenylketonuric patients showed the number of osteoclasts to be almost double that observed in controls (159.9 ± 79.5 and 87.8 ± 44.7, respectively; p = 0.001). Moreover, a strict direct correlation between the spontaneous osteoclastogenesis in PKU patients and the mean blood Phe concentrations in the preceding year was observed (r = 0.576; p = 0.010). An imbalance between bone formation and bone resorption might explain, at least in part, the pathogenesis of bone loss in this disease. These findings could provide new insights into the biological mechanisms underlying bone damage in PKU.