Ache

The FCR scale was based on examining past measures of this construct with a focus on anxiety or fear. Sixteen items were considered as candidates for the short versions. Through a consensus approach of cycling through these items between the authors and also piloting them with patients at the ECC to examine reactions to item wording we selected the final item pool. The four question scale (FCR4) was designed to feature anxiety, worry and strong feelings coupled with return of the disease (Q1–4). The longer seven question scale, to some extent was a compromise somewhat extending the item pool by featuring two items on the cognitive processing component that anxiety, fears or worries may interfere or potentially distort thoughts about cancer returning, Q5 and Q7. Finally, an item describing a behavioural response to FCR was included, Q6. Our approach for the FCR7 was to introduce additional items that were not simply variations of the first 4 items comprising the FCR4. One of the issues identified by patients when completing original formulations was the repetitive nature of some of the wording employed. Hence we introduced items that were worded with additional content (cognitive and behavioural) but possibly with substantial association with the core uni-dimensional construct. See Additional file 1: FCR7 for copy of Scale. The empirical data generated would enable inspection of the veracity of this approach.
To assist with validating the FCR measures (FCR4 and FCR7) a number of additional hypothetical constructs were assessed and their relationships tested using the construct validation approach outlined by Streiner and Norman [11 ]. This approach subsumes other forms of validity [12 (link)]. The Hospital Anxiety and Depression Scale (HADS) was administered [13 (link)]. We predicted that the FCR scales will be significantly related to anxiety and somewhat less so with depression, based upon a prior review [1 ], and adopting the two-factor model of the HADS measure [14 ]. In addition, a short number of single question items, were also included to assess the relationship with the total FCR scores. We included three items with 5 category ordinal rating scales ranging from ‘not at all’ to ‘all the time’. We deliberately chose statements that reflected some key areas known to be associated according to the three major components of Lee-Jones et al. model [15 (link)] of FCR derived from Leventhal’s self-regulation model (SRM), namely: representation of symptoms (‘Minor aches and pains remind me of cancer’), coping strategies (‘I just try to ignore feelings about the cancer returning’), and appraisal (‘In your opinion, what is your risk of having cancer recurrence?’). We expected the FCR scales to be positively associated with these components. We recognised that multi-item-scales are preferable to single items for assessing each of these components. However the inclusion of these clear statements reflecting the SRM would enable supportive evidence to be compiled. For example, a hypothesis was made that the avoidance coping strategy may not be as closely related to FCR as respondents may defer the process of accessing either, their fears, or admission of using avoidance [16 (link), 17 (link)].
Finally, patients who undergo mixed treatment protocols, and therefore believe their condition to be more complex and difficult to irradicate would tend to have raised FCR levels [1 ]. Recently, this has been confirmed in meta-analyses conducted by our group [18 , 19 ].

Activity 3 starts with the instructor explaining
that, after the interaction of the spike protein with the entry receptor
ACE2, cleavage of the S1 domain is achieved by a protease. Proteolytic
cleavage is followed by conformational changes in S2, which allows
the fusion of the virus with the cellular membranes leading to the
cytoplasmatic release of the viral genome into the host cell.^{15 (link)} Because the viral genome must access the cytoplasm,
every step of this process is important. Understanding the foundations
of these entry mechanisms allows researchers to design vaccines, antibodies,
small molecule inhibitors, and other potential therapeutics targeting
to prevent SARS-CoV-2 access into the host cell.
A brief outline
should be also provided to students about how the body fights illness
and how vaccines work. So, they must know that after bacteria or viruses
enter the human body they start to multiply, giving rise to infection
and causing disease. Immediately, the immune system is activated and
produces antibodies to fight off the infection, but this process requires
a few days, which is why we have symptoms such as fever, headache,
fatigue, or body aches. After the first infection, the immune system
will recognize the germ and will already know how to defend the body.
Vaccines contain attenuated or inactivated parts of a specific organism
which provoke a mimicked infection in the body helping the immune
system to create the specific antibodies. Of course, this simulated
infection can cause some symptoms which are common while the body
creates the new antibodies. Vaccines are the safest and most effective
way of protecting people from infections. Of course, they are not
perfect and a person can develop disease despite having been vaccinated,
although they will be at a much lower risk of becoming seriously ill.
Next, students load and overlay the structures with IDs: 7V2A,^{16 (link)}7TB8,^{17 (link)}7WPD,^{18 (link)}7CZP,^{19 (link)}7CZQ,^{19 (link)} and 7JZL(20 (link)) (Figure S5).
All are complexes of the spike
protein with antibodies or inhibitors
bonded to the receptor binding domain (RBD). They must answer the
following two questions: (1) why do SARS-CoV-2 vaccines prevent
serious illness and save hundreds of thousands of lives? And
based on what they have learned: (2) what could be the influence
of virus variants on the efficacy of these antibodies, and why?At the end of these activities, most of the students made
the connection
between the observed structural features and the efficacy of vaccines,
concluding by themselves that antibodies or inhibitors act by blocking
the ACE2 binding of the spike protein and, as consequence, the viral
entry into the host cells.
During the sessions, the students
explained to the instructors
their respective answers to the questions and the instructors evaluated
them. In addition, a quick assessment of the student’s learning
can be done using a short questionnaire as such the one provided in
the SI. If desired, it can be carried
out with Kahoot or similar tools.

All patients with T2DM were asked whether they had numbness, pain (prickling or stabbing, shooting, burning or aching pain), and paresthesia (abnormal cold or heat sensation, allodynia and hyperalgesia) in the toes, feet, legs or upper-limb. Then, an experienced physician performed the neurologic examination which included vibration, light touch, and achilles tendon reflexes on both sides in the knee standing position (as being either presence or weakening or loss). Vibration perception threshold (VPT) was assessed at the metatarsophalangeal joint dig I using a neurothesiometer (Bio- Thesiometer; Bio-Medical Instrument Co., Newbury, OH, USA). First, the patients were informed how to know the vibration sensation is felt by gradually turning the amplitude from zero to maximum, then the test began again from zero and they were asked to say the moment that they first felt it. Measurements were made on the planter aspect of the big toe bilaterally, three times consecutively for each big toe. The median of three readings is accepted as the VPT value of that measurement (35 (link)). Sensitivity to touch was also tested using a 5.07/10-g Semmes-Weinstein monofilament (SWM) at four points on each foot: three on the plantar and one on the dorsal side. The 10-g SWM was placed perpendicular to the skin and pressure was applied until the filament just buckled with a contact time of 2 s. Inability to perceive the sensation at any one site was considered abnormal (36 (link), 37 (link)). DPN was defined as VPT ≥25 V and/or inability to feel the monofilament (35 (link)), and then participants were divided into DPN group and no DPN group.
Ankle brachial index (ABI) was measured noninvasively by a continuous-wave Doppler ultrasound probe (Vista AVS, Summit Co., USA) with participants in the supine position after at least 5 min of rest. Leg-specific ABI was calculated by dividing the higher SBP in the posterior tibial or dorsalis pedis by the higher of the right or left brachial SBP (33 (link), 38 (link)). Patients were diagnosed as having PAD if an ABI value <0.9 on either limb (33 (link), 38 (link)).
DFU was defined as ulceration of the foot (distally from the ankle and including the ankle) associated with neuropathy and different grades of ischemia and infection (39 (link)).