Paeds - Endocrine, Oncology, Neonatal Flashcards
what is congenital hypothyroidism?
child is born with an underactive thyroid gland. This occurs in around 1 in 3000 newborns.
what two ways does congenital hypothyroidsm occur
dysgenesis - thyroid gland is underdeveloped
dyshormonogenesis - fully developed gland that does not produce enough hormone
how is congenital hypothyroidism picked up
newborn blood spot screening test
what is the presentation of congenital hypothyroidsm (6)
-poor feeding
-constipation
-increased sleeping
-reduced activity
-slow growth and development
-prolonged neonatal jaundice
what is hashimotos thyroiditis
an acquired autoimmune hypothyroidism leading to inflammation of the thyroid gland
what antibodies is hashimotos thyroiditis associated with (2)
-antithyroid peroxidase (anti-TPO)
-antithyroglobulin antibodies
Sx of hashimotos thyroditis
-Fatigue and low energy
-Poor growth
-Weight gain
-Poor school performance
-Constipation
-Dry skin and hair loss
Ix of hypothyroidism (3)
thyroid function blood tests (TSH, T3 and T4), thyroid ultrasound
thyroid antibodies
Mx of hypothyroidism
Levothyroxine once daily
risk factors for undescended testes (5)
Family history of undescended testes
Low birth weight
Small for gestational age
Prematurity
Maternal smoking during pregnancy
What is cryptorchidism
A congenital condition where the testis fail to reach the bottom of the scrotum by 3 months of age
Complications of cryptorchidism
-risk of infertility
-increased risk of testicular seminoma (cancer)
-testicular torsion
Tx of cryptorchidism (3)
Orchidopexy at 6- 18 months of age - mobilisation of testis into dartos pouch ( bottom of scrotum)
Intra-abdominal testis - evaluated laparoscopically and mobilised.
Past 2 years
Orchidectomy as decreased risk of malignancy
What is retractile testicles
Before puberty the testes move out the scrotum into the inguinal canal due to cremasteric reflex
Sometimes do not come back down and need orchidopexy
what is hypogonadotropic Hypogonadism
deficiency in LH and FSH (gonadotrophins)
leading to a deficiency in oestrogen and testosterone
what is the root cause of hypogonadotrophic hypogonadism
abnormal functioning of pituitary gland
give 5 causes of hypogonadotropic Hypogonadism
-damage to hypothalamus or pituitary
-tumours - astrocytomas, craniopharygiomas, prolactinomas
-GH deficiency
-Hypothyroidism
-Hyperprolactinameia (high prolactin)
-CF - delay puberty
-IBD - delay puberty
-kallmans syndrome
-excessive exercise or dieting -delays menstruation in girls
-bulimia
what is kallmans syndrome
-genetic condition resultig in the failure to start puberty and an impairment in smell
what is kallmans syndrome associated with
anosmia - absent smell
investigations for delay in puberty
categories
1. initial (3)
2. hormonal blood tests (4)
3.genetic tests (2)
4 imaging (3)
initial
-FBC + ferritin for anaemia
-U+E - for CKD
-Anti TTG/ anti EMA - coeliac
hormonal blood tests
-early morning LH + FSH - low in hypogonadotropic Hypogonadism
-TFTs
-GH tests - insulin like growth factor
-serum prolactin
Genetic testing
-kleinfelters
-turners
(can both cause delayed puberty
Imaging
-xray of the wrist to assess bone age
-pelvic ultrasound - assess ovaries
-MRI of the brain - pituitary pathology + assess olfactory bulbs (kallmans syndrome)
what is HYPERgonadotropic hypogonadism
- gonads dont respond to stimulation from the gonadotrophins (LH and FSH)
- There is no negative feedback from the sex hormones (testosterone and oestrogen),
-so anterior pituitary produces increasing amounts of LH and FSH to try harder to stimulate the gonads
what are the potential causes of hypergonadtropic hypogoandism
is due to abnormal functioning gonads
genetic:
-kleinfelters
-turners syndrome
-congenital abscence of the ovaries or testes
-previous damage to the gonads e.g testicular torsion
Management for a delay in puberty
-treat the underlying condition e.g GH deficiency
-replacement of sex hormones to induce puberty
what inheritance pattern is kallmanns syndrome
x linked recessive
features of kallmanns sydnrome
-delayed puberty
-hypogonadism
-cryptorchidism
-anosmia
-sex hormone levels low
-low FSH and LH
-patients above average height
-cleft lip
-visual/ hearing defects
Mx of kallmanns syndrome
-testosterone supplementation
-Gonadatrophin (LH/FSH) supplementation
typical epidemiology of kallmanns syndrome
lack of smell in a boy with delayed puberty
what is androgen insensitivity syndrome
condition where cells are unable to respond to androgen hormones due to a lack of androgen receptors
what inheritance pattern is androgen insensitivity syndrome
X linked recessive
Sx of androgen insensitivity syndrome
-lack of pubic hair + facial hair
-taller in height - female
-infertility
-primary amenorrhoea - abscence of menstruation
-undescended testes
-breast developement
Why do males with androgen insensitivity syndrome develop external female characteristics
-the males produce testosterone but there is no response to it
-there is also conversion of additional androgens to oestrogen
-this leads to a female phenotype externally
Presentation of someone with androgen insensitivity syndrome
-inguinal hernias containing testes in infancy
-primary amennorrhoea at puberty
Mx of androgen insensitivity syndrome
Bilateral orchidectomy - to avoid testicular cancer
Oestrogen therapy
Vaginal dilators and vagina surgery to create adequate vaginal length
Counselling - understand how to live with condition socially and sexually - normally raised as female
How to diagnose androgen insensitivity syndrome (2)
-buccal smear/ chromosome analysis to reveal 46 XY chromosome
-post puberty testosterone levels will be higher than normal
What is congenital adrenal hyperplasia
Congenital deficiency of 21 hydroxylase enzyme causing underproduction: Cortisol + Aldosterone
Overproduction of androgens
Inheritance pattern of Congenital adrenal hyperplasia
Autosomal recessive
Give three examples of steroid hormones
Androgens - e.g Testosterone
Glucocorticoids- e.g Cortisol
Mineralcorticoids - e.g Aldosterone
Pathophysiology of congenital adrenal hyperplasia
-21 hydroxylase normally converts progesterone into aldosterone and cortisol
-progesterone is also used to create testosterone
-the defect in the 21 hydroxylase means extra progesterone circulates with less conversion to
Aldosterone and cortisol
-gets converted to testosterone
Levels in Congenital adrenal hyperplasia in
Aldosterone
Cortisol
testosterone
Aldosterone - low
Cortisol - low
testosterone -high
How to diagnosis Congenital adrenal hyperplasia
-ACTH simulation testing measures adrenal gland response to ACTH
-newborn screen - not offered in UK
Presentation in MILD cases of congenital adrenal hyperplasia
Female patients - virilization (more manly)
Tall for age
Deep voice
Early puberty
Hyperpigmentation
Facial hair
Absent periods
Male patients
Tall for age
Deep voice
Early puberty
Hyperpigmentation
Large penis
Small testicles
Presentation of severe cases of Congenital adrenal hyperplasia
-ambiguous genitalia in females
-enlarged clitroris (due to high testosterone)
-skin pigmentation -due to ACTH
-salt wasting crisis which can lead to: - too little aldosterone
Poor feeding
Arrhythmias
Dehydration
Vomiting
In CAH what is salt wasting crisis and what three conditions does this cause
LIFE THREATENING
-adrenal glands make too little aldosterone, causing the body to be unable to retain enough sodium
-leads to hyponatraemia, hypoglycaemia + hyperkalemia
Why skin hyperpigmention in CAH
-anterior pituitary gland responds to the low levels of cortisol by producing increasing amounts of ACTH
-A byproduct of the production of ACTH is melanocyte simulating hormone.
-This hormone stimulates the production of melanin (pigment) within skin cells.
Mx of CAH (3)
See paediatric endocrinologist
-Cortisol replacement - hydrocortisone,
-Aldosterone replacement - fludrocortisone
-Female patients with ambiguous genitals may require corrective surgery
What are gliomas
Tumours of the brain and spinal cord
What are the three types of glial cells
astrocytes
oligodendrocytes
ependymal cells
Types of gliomas - which one is most malignant
Astrocytoma (the most common and aggressive form is glioblastoma)
Oligodendroglioma
Ependymoma
Tx of gliomas
Radiation and chemotherapy
-correct hormone imbalances if necessary
What condition may increase risk of hypothalamic tumours
Neurofibromatosis
Sx of hypothalamic tumours
-euphoric sensations
-failure to thrive
-headache - fluid can collect in brain
-hyperactive
-loss of appetite
-vision loss
-seizures
What is precocious puberty
onset of secondary sexual characteristics in children at an age that is two standard deviations younger than the mean age of pubertal onset
What are the two types of precocious puberty
central + Peripheral
What is central precocious puberty
-early maturation of hypothalamic+pituitary gonadal axis
-early release of LH+FSH
-increases sex hormones
Causes of central precocious puberty
-largely idiopathic
-infection/cyst
-radiation damage to brain (reduced -ve feedback)
-GnrH secreting tumour
What is peripheral precocious puberty
Overproduction of sex hormones by gonads (GnRH independent)
Causes of peripheral precocious puberty (5)
-cyst/tumour
-genetic condtions - mccune Albright syndrome
-thyroid/ adrenal dysfunction
-exogenous hormones e.g creams
How to diagnose precocious puberty
-Tanner scale
-GnRH levels - see if dependent (central) or independent (peripheral)
-ultrasound/MRI - to look for abnormalities
Tx of precocious puberty
GnRH analogues - reduce LH/FSH production
Surgery to remove cyst/ tumour
What is testicular torsion
Twisting of the spermatic cord with rotation of the testicle which can lead to ischemia and necrosis
Presentation of testicular torsion
-Sudden onset severe scrotal pain,
-Abdominal pain - in boys always rule out TT
-nausea + vomiting.
-Tender testis.
-Overlying scrotal skin may be reddened and oedematous.
What is bell clapper deformity
RISK FACTOR FOR TESTICULAR TORSION
where the fixation between the testicle and the tunica vaginalis is absent so the testicle hangs in the horizontal postion and is more able to twist
Mx of testicular torsion
SEEN WITHIN 6 HOURS
-Nil by mouth, in preparation for surgery
-Analgesia as required
-Urgent senior urology assessment
-Surgical exploration of the scrotum
-Orchiopexy (correcting the position of the testicles and fixing them in place)
-Orchidectomy (removing the testicle) if the surgery is delayed or there is necrosis
What is whirlpool sign in testicular torsion
-In an ultrasound scan used to confirm the diagnosis
- will see a spiral appearance of the spermatic cord and blood vessels
What are the examination findings of testicular torsion
-absent cremasteric reflex
-elevated testicle
-firm swollen testicle
-abnormal lie (horizontal)
-epididymis in wrong place
What is wilms tumour
Specific type of tumour affecting the kidney in children, typically under the age of 5 years.
Presentation of wilms tumour
mass in abdomen
Abdominal pain
Haematuria
Lethargy
Fever
Hypertension
Weight loss
Dx of wilms tumour
initial investigation
-ultrasound of the abdomen to visualise the kidneys.
-A CT or MRI scan used to stage the tumour.
-Biopsy to make a definitive diagnosis.
Mx of Wilms tumour
-surgical excision of the tumour along with the affected kidney (nephrectomy).
Adjuvant therapy
-radiotherapy
-chemotherapy
Which tumour most commonly spread to brain
lung (most common)
breast
bowel
skin (namely melanoma)
kidney
Most common brain tumour in children
Pilocytic astrocytoma
Tx of medullobalstoma
Treatment is surgical resection and chemotherapy.
What is craniopharygioma
solid/cystic tumour of the sellar region that is derived from the remnants of Rathke’s pouch
Presentation of craniopharyngioma
hormonal disturbance
symptoms of hydrocephalus
bitemporal hemianopia.
What will you find on imaging on glioblastoma multiforme
solid tumours with central necrosis and a rim that enhances with contrast.
Mx of pituitary tumours
-Trans-sphenoidal surgery (through the nose and sphenoid bone)
-Radiotherapy
-Bromocriptine to block excess prolactin
-Somatostatin analogues (e.g., octreotide) to block excess growth hormone
Presentation of pituitary tumours
Bitemporal hemianopia
Cushings sx moon face, purple striae
Acromegaly sx big hands and jaw, headaches
Hyperprolactoinaemia sx galactorrhea, amenorrhea
Thyrotoxicosis sx palpitations, anxiety, fatigue
What are acoustic neuromas
benign tumours of the Schwann cells that surround the vestibulocochlear nerve that innervates the inner ear
What condition are acoustic neuromas associated with
neurofibromatosis type 2.
Presentation of acoustic neuromas
Unilateral sensorineural hearing loss (often the first symptom)
Unilateral tinnitus
Dizziness or imbalance
Sensation of fullness in the ear
Facial nerve palsy (if the tumour grows large enough to compress the facial nerve)
1st line investigation in patients with brain tumours
MRI scan
Presentation of retinoblastoma
abnormal light reflex - White pupillary reflex
squint
visual deterioration
What is a retinoblastoma?
A malignant tumour of retinal cells
What secondary malignancy can occur in retinoblastoma?
Sarcomas (soft tissue cancer)
Osteosarcoma (bone)
What is the treatment of retinoblastoma?
-Chemotherapy followed by local laser treatment to the retina
-Radiotherapy
-Enucleation of the eye - removal of eye from muscles and tissue
What marker is raised in hepatoblastoma?
Serum Alpha feto protein
Treatment of hepatoblastoma (3)
Chemotherapy, e.g. platinum drugs and anthracyclines
Surgical resection
Liver transplant
What are the two types of bone cancer in children?
Ewing sarcoma
Osteogenic sarcoma - more common
Which gender is more likely to get bone tumours?
Males
Presentation of bone tumours
Persistent localised bone pain usually present in limbs
Management of bone tumours
Chemotherapy before surgery
En block resection - removal of tumour without removal of its capsule
Radiotherapy – only in Ewing sarcoma
What are neuroblastomas?
Tumours that arise from neural crest tissue in the adrenal medulla and sympathetic nervous system
Presentation of neuroblastoma
Usually an abdominal mass present
Weight loss
Pallor
Hepatomegaly
Bone pain
Limp
Less common:
Paraplegia
Skin nodules
Raccoon eyes
Proptosis
Investigations for neuroblastoma (4)
Bloods + urine - raised Catecholamines (hormones produced in adrenal glands
Biopsy
Ultrasound of abdomen
MIBG scan - neuroendocrine cells absorb so you can map and see abnormalities
Management of neuroblastoma
Nonmetastatic
Surgery
Metastatic disease
Chemotherapy
Surgery
Radiotherapy
Retinoic acid - reduces recurrence
Risk factors for hypoglycaemia in first 24 hours of life
-too small for gestational age - intrauterine growth restriction
-polycythaemia
-maternal diabetes mellitus
-prematurity
-hypothermia
Mx of hypoglycaemia in newborns
Prevention - early and frequent milk feeding
Monitor blood glucose
Increased risk of hypoglyceamia - regularly monitor blood glucose
If blood glucose below 2.6/ symptomatic :
IV dextrose to maintain above 2.6
IM glucagon
How should you administer high concentrations of glucose in someone with hypoglyceamia and why?
Central venous catheter
To avoid:
Reactive hypoglycemia - too much insulin produced in response causing reactive dip in BG
Extravasation(leakage) into the tissues - lead to skin necrosis
Sx of hypoglycaemia in neonates
-Cyanosis
-apnoea
-seizures + tremors
-sweating
-irritability
-hypotonia
-difficulty feeding
-lethargy
How is nocturnal hypoglycaemia treated
Bolus insulin regimes
Snacks at bedtime to regulate throughout the night
What is respiratory distress syndrome
A disease affecting premature neonates born before the lungs start to produce enough surfactant
Pathology of respiratory distress syndrome
-Inadequate surfactant leads to high surface tension within alveoli.
-This leads to atelectasis (lung collapse), as it is more difficult for the alveoli and the lungs to expand.
-This leads to inadequate gaseous exchange, resulting in hypoxia, hypercapnia (high CO2) and respiratory distress.
Mx of respiratory distress syndrome
-dexamethasone - allows for maturation of lungs and increased surfactant production
Premature neonates may need:
Intubation and ventilation- fully assist breathing
Endotracheal surfactant- artificial surfactant
Continuous positive airway pressure (CPAP) - keep lungs open
Supplementary oxygen
Complications of respiratory distress syndrome
Short term
Long term
Short term:
Pneumothorax
Infection
Apnoea
Intraventricular haemorrhage
Pulmonary haemorrhage
Necrotising enterocolitis
Long term:
Chronic lung disease of prematurity
Retinopathy of prematurity
Neurological, hearing and visual impairment
What is the investigation for respiratory distress syndrome
Chest X- ray
* ground glass appearance of lungs
*Air bronchogram - heart borders become obscured due to lungs being more opaque
ABG- check blood oxygen
Clinical signs of RDS
-tachypnoea - 60 breaths per minute +
-laboured breathing
-recessions
-tracheal tug
-nasal flaring
-expiratory grunting
-cyanosis - if severe
What is bronchopulmonary dysplasia?
A breathing disorder in premature infants resulting from poor lung growth
What is the prevention of bronchopulmonary dysplasia
-corticosteroids to mothers that show signs of pre term labour at less than 36 weeks
-Use of CPAP
-caffeine to stimulate respiratory effort
-not over oxygenating
Mx of bronchopulmonary dysplasia (6)
Corticosteroids given to mothers showing signs of prematurity
CPAP for the neonate
Caffeine- stimulated respiratory effort
Not over oxygenating
Sleep study - assess o2 sats during sleep
Home low dose oxygen - slowly weaned off
RSV protection for bronchiolitis - monthly injection of palivizumab
Clinical feature of bronchopulmonary dysplasia
-low oxygen saturations
-increased work of breathing
-poor weight gain
-poor feeding
-wheeze
-crackles
-increased susceptibility to infection
What is meconium aspiration
Where the baby passes meconium in the womb and swallows it into the lungs
Sx of meconium aspiration
-cyanosis
-breathing problems
-greenish amniotic fluid
-limpness of infant
-coarse crackles
-bradycardia
Tx of meconium aspiration (5)
-large bore suction Catheter
-if bradycardic then CPAP
-Abx to treat any infection
-maintain body temperature
-chest tapping to loosen secretions
Dx of aspiration Pneumonia (4)
-fetal monitor - shows bradycardia
-abnormal breath sounds - coarse crackles
-capillary blood gas - acidosis, decreased oxygen and increased CO2
-CXR- streaky areas on lungs
What is hypoxic ischemic encephalopathy
A lack of oxygen during birth causing lack of oxygenated blood flow to the brain leading to brain damage (encephalopathy)
Biggest complications of HIE
Cerebral palsy
Causes of HIE
Intrapartum haemorrhage
Maternal shock
Prolapsed cord - compression of cord during birth
Nuchal cord - cord wrapped around the neck Of baby
Mx of HIE
Supportive care
-neonatal resuc
-ventilation
-acid base balance
-circulatory support
-therapeutic hypothermia
What is therapeutic hypothermia for HIE
Reduce inflammation and neurone loss after hypoxia by:
-actively cooling the core temperature of the baby
-using cooling blankets and hat
-between 33-34 degrees using a rectal probe
-gradually warmed to a normal temp
What is sarnat staging of HIE
Mild:
Poor feeding, generally irritability and hyper-alert
Resolves within 24 hours
Normal prognosis
Moderate:
Poor feeding, lethargic, hypotonic and seizures
Can take weeks to resolve
Up to 40% develop cerebral palsy
Severe:
Reduced consciousness, apnoeas, flaccid and reduced or absent reflexes
Up to 50% mortality
Up to 90% develop cerebral palsy
What are the TORCH infections
Toxoplasmosis gondii
Other - VSV, parvovirus B19, HIV, syphilis
Rubella
CMV
HSV
What are torch infections
Infection of the developing fetus hat can occur IN UTERO, DURING DELIVERY or AFTER BIRTH
Complications of TORCH infections
Preterm birth
Delayed development
Physical malformations
Loss of pregnancy
How are torch infections passed to fetus (3)
-through placenta
-passing through birth canal
-breastfeeding
How is toxoplasmosis gondii transmitted originally
Consumption of undercooked meats
Exposure to cat faeces
Signs and symtoms of toxoplasmosis
Cory has a big head and likes stiff calcium jerky
Cory -Chorioretinitis
Big head - hydrocephalus
Stiff - rigidity
Calcium - intracranial calcifications
Jerky - seizures
general TORCH infection signs and symptoms
Microcephaly
Low birth weight
Sleepiness
Cataracts
Hearing loss
Hepatosplenomegaly
Purpura or petechiae
Jaundice
Seizures
Deafness
Classic triad of features on congential toxoplasmosis (CHI)
- Chorioretinitis (inflammation of the choroid and retina in the eye)
Intracranial calcification - Hydrocephalus
- Intracranial calcification
How is CMV trasmitted
Direct contact with bodily fluids:
-Semen
-tears
-saliva
-mucus
-vaginal fluids
Presentation of CMV in children (6)
Janice, peri, cory are pure death
-jaundice
-periventricular calcifications + microcephaly
-inflammation of eye (chorioretinitis)
-pinpoint petechial blueberry muffin type rash
-deafness (sensorineural)
What is the common cellular presntation of CMV
Owls eye appearance of infected cells
-due to intranuclear inclusion bodies
Tx for CMV
Gangciclovir - antiviral that can reduce risk of hearing loss and microcephaly
Tx for congenital toxoplasmosis gondii (2)
Pyrimethamine - anti parasitic medication
&
Sulfadiazine - antibiotic
How are the different types of HSV transmitted
HSV-1 trasmitted through oral secretions (cold sores)
HSV-2 trasmitted sexually
Features of herpes simplex virus
Gingivostomatitis - inflammation of oral mucosa
Cold sores
Genital ulcerations
Mx of HSV
gingivostomatitis: oral aciclovir/chlorhexidine mouthwash
cold sores: topical aciclovir
genital herpes: oral aciclovir
When is spiramycin given in TORCH infections and what is it
Spiramycin - ABX and antiparastic
Given to mothers who have early detected toxoplasmosis during pregnancy to reduce transmission to fetus
What is the management of HSV in pregnant mother
-elective caesarean at term
-women with recurrent herpes - suppressive therapy aka acyclovir
Main investigation for HSV
Viral cultures + PCR
CMV main investigations
-DNA detection on PCR
-viral culture
-CMV specific immunoglobulin M antibody measurements
What is cleft lip and palate
Congenital malformation in the upper lip, oral cavity and roof of mouth due to improper fusion of facial bones and tissues
Three types of cleft lip and palate
Cleft lip
Cleft palate -uvula commonly also split
Combination - split alveolar ridge and uvula
Risk factors for cleft lip and palate
Genetic condtions- pataus, stickler syndrome
Folate deficiency during development
Hypoxia in uterus
Pesticide exposure
Complications of cleft lip and palate (4)
Speech impediment
Hearing issues
Recurrent otitis media
Difficulty eating
Signs and sx of cleft and palate
Dysphonia - hypernasal voice
Dysarthria
Nasal cavity infection - food gets trapped in nasal cavity
Velopharyngeal insufficiency - causes speech problems
How to diagnose cleft lip and palate (3)
Prenatal ultrasound - helps evaluate the nares and upper lip
MRI
CT scan/ X-ray
Tx of cleft lip and palate
Surgical closure by three months of age
Prostethic implants
Speech and language therapy
Prevention:
Folate supplementation during pregnancy
Presntation of HSV encephalitis (6)
Altered consciousness
Altered cognition
Unusual behaviour
Acute onset of focal neurological symptoms
focal seizures
Fever
Dx of HSV encephalitis (5)
-LP + PCR
-CT scan if a lumbar puncture is contraindicated
-MRI scan after the lumbar puncture to visualise the brain in detail
-EEG
-Swabs of other areas can help establish the causative organism, such as throat and vesicle swabs
-HIV testing is recommended in all patients with encephalitis
Give some contraindications for LP (4)
-GCS below 9
-haemodynamically unstable,
-active seizures or post-ictal.
-meningococcal septicaemia
Tx for HSV encephalitis
- Aciclovir - started if encephalitis is suspected
- Repeat LP to ensure success TX
Complications for encephalitis
Seizures
Hormone imbalance
Learning disability
Changes to memory
Changes in mood
Lasting fatigue
Osteosarcoma
Ewing sarcoma
Chondrosarcoma
X - ray finding
OsteoSarcoma= Sunburst pattern
Ewings sarcoma= OnEwin (onion skin)
Chondrosarcoma= PopChon (popcorn calcification
3 clinical signs of syphilis in babies (5)
Hutchinsons triad
-Hutchinson teeth - small notched teeth
-CN8 nerve palsy
-interstitial keratitis
-also saber shins and saddle nose
